bluuebunny/crossref_metadata_2025 huggingface dataset:
CaM kinase I binds and regulates p53 in breast cancer cells (613.2)
Authors: Geck Renee , Schmitt John
Published: June 2021

P53 is a tumor suppressor protein that regulates gene expression and cell cycle progression. Calcium/calmodulin‐dependent protein kinase (CaM kinase) proteins, including CaM KK and CaM KI, are known to control ERK and several transcription factors. CaM KI has also been shown to bind and phosphorylate the cell cycle protein p27 to promote cell cycle progression. Interestingly, p53 contains a possible CaM KI phosphorylation site at S366. Our goal was to evaluate the ability of CaM KI to bind and regulate p53 as well as investigate its effects on p53 phosphorylation, the cell cycle, and cell growth in MCF‐7 and MDA‐MB‐231 breast cancer cells. GST pull‐downs showed that CaM KI associates with phosphorylated p53 at S366. Treatment of MCF‐7 cells with estrogen (E2) increases the endogenous association of CaM KI‐p53 as does treatment of MDA cells with the calcium‐elevating agent, ionomycin. None of the treatments led to an association of p53 with CaM KK, CaM KII, or CaM KIV. Interestingly, E2 increased MCF‐7 progression through the cell cycle and MCF‐7 cell growth, effects enhanced by inhibiting p53 with PFT‐α. In summary, our data suggests that CaM KI binds and phosphorylates p53 in MCF‐7 and MDA cells, and that E2 and PFT‐α stimulate MCF‐7 cell growth through a novel CaM KI‐p53 pathway.

Grant Funding Source: Supported by M.J.Murdock Charitable Trust #2011267
Profiling of human normal and cancer cell lines using phenotype microarray analysis (613.5)
Authors: Parmar Nitika , Wetton Nichole , Alvarado Shelley , Kennedy Shane
Published: June 2021

The aim of this research project was to study how women’s cancer cell lines respond to anti‐cancer agents and whether the mTOR pathway was being targeted in them. Five cancer cell lines were used‐ two ovarian (OV90, TOV112D), two uterine (MES‐SA, KLE), one breast (SKBR) and one non‐cancerous kidney (HEK293). BIOLOG Phenotype Microarray anti‐cancer panels were used to profile these cell lines. Cells were seeded on a variety of BIOLOG panels consisting of 96 different anti‐cancer agents for 24‐36h. Cell growth was examined using a MTT cell proliferation assay. Six reagents‐ berberine chloride, azathioprine, celastrol, gossypol, miltefosine, and etoposide, had the largest growth impact on the cell lines. Cell lines were then treated with 5µM of these reagents and then subjected to the InstantOne Elisa assay to determine activation status of a protein‐pS6 kinase in the mTOR pathway. Cancer cells from different tissues responded differently to the same anti‐cancer agent; HEK293 cells showed maximum resistance to treatment with these compounds. The reagents were then used at doses varying from 0.05‐5μM to conduct a dose response profile. Growth inhibition was observed at a concentration of 0.5μM and above, in a cell line specific manner. Appropriate controls were used in all experiments. Our collective findings indicate that growth inhibition observed in some cell lines is due to the inhibition of the mTOR pathway.

Grant Funding Source: Supported by the California State University Program for Education and Research in Biotechnology
Inhibition of ammonia oxidation in the thermophilic ammonia‐oxidizing archaeon Nitrosocaldus yellowstonii (617.6)
Authors: Gelsinger Diego , Cassani Madeline , Jewell Talia , de la Torre Jose
Published: June 2021

Molecular data suggests ammonia‐oxidizing archaea (AOA) play an important role in nitrogen cycling. In particular, organisms related to the thermophilic archaeon Nitrosocaldus yellowstonii appear to be the only nitrifiers present in terrestrial hydrothermal systems at temperatures above 65°C. To better understand the contribution these thermophilic archaeal nitrifiers have in geochemical processes such as nitrogen cycling, we need tools to manipulate their metabolic activity in laboratory cultures and in situ. Nitrosocaldus yellowstonii HL72 is a thermophilic AOA cultivated from a hot spring in Yellowstone National Park (Wyoming, USA). To understand how N. yellowstonii contributes to nitrogen cycling in hot springs, we must first characterize the effect of nitrification inhibitors on its metabolic function. In this study, we have focused on allylthiourea (ATU), a commonly‐used inhibitor of nitrification. We have shown that ATU is stable at temperatures up to 72°C, the growth temperature of N. yellowstonii. Ammonia oxidation in N. yellowstonii is completely inhibited by ATU concentrations of 1 mM, concentrations that are approximately 100 times higher than those required to inhibit ammonia oxidation in bacteria. Addition of 1 mM ATU decreased the rate of nitrite production of N. yellowstonii from 0.039 ± 0.001 mM/h‐1 prior to addition, to 0.001 ± 0.001 mM/h‐1. Because nitrite is used for a proxy of growth, quantitative PCR was used to measure cell numbers for the single copy gene amoA per cell. There was no change in amoA copy number after the addition of 1 mM ATU while the unamended control continued to exponentially increase, further confirming that the addition of 1 mM ATU halted cell growth completely. RT‐qPCR showed amoA expression decreased 23.5% and 47.9% compared to the unamended control, two and four hours after ATU addition. We conclude that ATU is an effective inhibitor of AOA cell growth and is will be a useful tool to manipulate metabolic activity of AOA in hot spring systems.

Grant Funding Source: Supported by NIH MARC T34‐GM00857
Genomics Education Partnership: a research‐based approach to undergraduate teaching utilizing a centralized support system (618.39)
Authors: Goodman A. , Arrigo C. , Barral A. , Jones K. , Peterson C. , Roecklein‐Canfield J , Leung W , Shaffer C. , Lopatto D. , Elgin S.
Published: June 2021

The Genomics Education Partnership (GEP) is a consortium of educators with common research and educational goals in genomics, and is comprised of 100+ faculty members instructing 1000+ students annually. Our focus is 1) undergraduate education via research in comparative genomics and 2) assessment of pedagogy within diverse student populations. To examine the evolution of the Drosophila “dot” chromosome, students in GEP courses improved over 7 Mb of genomic sequence and generated over 1000 manually curated gene models. To assess pedagogy, we evaluated student learning gains in both the cognitive domain (pre‐ and post‐course knowledge quiz) and the affective domain (pre‐and post‐course CURE survey). We find that institutional characteristics have little impact on student outcomes, while the instructional time spent on the GEP projects has a significant impact on student experience. Cognitive learning gains are observed in both short and long implementation formats, and across a wide range of cognitive skill levels. However, only longer time investments show student benefits commensurate with those reported for students conducting summer research. A survey of faculty participants reveals that a centralized support system is critical for sustaining GEP. In summary, our data suggest that a research‐based curriculum with centralized support is a successful approach in STEM education.

Grant Funding Source: Supported by grant #52007051 from the HHMI to SCRE and by the Washington University in St. Louis
Identification of biosynthetic gene clusters from sponge‐associated microbes (618.44)
Authors: O'Hara Danielle , Craig Connor , Mahan Marielle , Datteibaum Jonathan
Published: June 2021

Greater than 90% of microbes living in soil are unculturable due to the complex nutrient and temperature conditions required for growth. These microorganisms represent a potential untapped source of natural products that may be developed for biotechnological and pharmaceutical uses. Most notably, microorganisms with phosphopantetheinyl transferase (PPTase) activity are of high interest due to the role PPTase has in activating non‐ribosomal peptide synthetase (NRPS) and polyketide synthetase (PKS) gene clusters. These gene clusters synthesize complex natural products utilized by the microorganism or its host for selective advantages. We screened for the presence of NRPS and PKS gene clusters in several pigmented microbes previously isolated from a Chesapeake Bay sponge (Clathria prolifera). Genomic DNA was isolated from each of these microbes and we attempted to construct metagenomic libraries. We goal is to screen the libraries for PPTase activity. We extended this study to include microbial DNA isolated from soil samples taken around the University of Richmond campus. The isolated environmental DNA (eDNA) was tested for the presence of NPRS and PKS gene clusters as well. This on‐going project seeks to identify new biosynthetic gene clusters from microbial sources.

Grant Funding Source: University of Richmond Arts and Sciences
Micronutrient supplementation during pregnancy and the preschool years and child behavior at 7‐9 years of age (619.3)
Authors: Murray‐Kolb Laura , Bahnfleth Charlotte , Hurley Kristen , Cole Pamela , Khatry Subarna , LeClerq Steven , Christian Parul
Published: June 2021

We examined parent and teacher behavior ratings (Conners’) of 7‐9 y Nepali children who received, in RCTs, daily micronutrients by maternal supplementation during pregnancy (placebo:pPL, iron/folic acid:pIFA, iron/folic acid/zinc:pIFAZn, multiple micronutrients:pMM), and/or directly at 12‐35 mo (cPL, cIFA, cZn, cIFAZn) or not. Differences in scores were examined relative to PL within each supplementation time point, adjusting for confounders. Our analyses of Conners’ data revealed two factors for parent scores (P‐hyperactive/oppositional & P‐inattentive) and teacher scores (T‐hyperactive & T‐inattentive). Children in the pMM grp had lower scores (fewer problems) on both parent factors and those in the pIFA grp had lower scores on P‐hyperactive/oppositional vs pPL. Supplementation at 12‐35 mo revealed lower scores on P‐hyperactive/oppositional for cZn vs cPL. We also examined timing of IFA supplementation by comparing the following 2x2 combinations: pPL, cPL; pPL, cIFA; pIFA, cPL; pIFA, cIFA. Scores on P‐hyperactivity/oppositional were lower in pIFA, cPL vs pPL, cPL grp and did not differ between other grps. Scores on P‐inattention and T‐hyperactivity did not differ between grps. For T‐inattention, the worst scores were in the pIFA, cIFA grp, suggesting supplementing with IFA during both pregnancy and preschool years does not confer added benefit to later child behavior and may reduce the effects of pregnancy supplementation alone. In conclusion, antenatal IFA supplementation may be beneficial for later child behavior and Zn supplementation during preschool years may have modest effects in this South Asian setting.

Grant Funding Source: Supported by: NICHD and Gates Foundation
An international study of food behavior and nutritional status of children from 21 countries (620.13)
Authors: Hartwick Carol Anne , Moreno Luis , Fisberg Mauro , Hart Kathryn , Fielding Barbara , Lenham‐New Susan , Richards Zoe
Published: June 2021

The Danone Nations Cup (DNC) is an annual international soccer tournament for school‐aged children. It comprises 32 national final competitions and one world final event annually, involving more than 2.5 million children from up to 40 countries worldwide. The DNC’s ambition is to engage with and promote physical activity, inter‐cultural values, and healthy food habits to children.

The Danone Institute International, a non‐for‐profit organisation promoting human health, designed an innovative health promotion intervention for the event, based on food appreciation and basic nutritional knowledge.. A collaborative project, Fit Food, gathered data on children’s 1) nutritional knowledge; 2) social behavior in a multi‐cultural food environment; 3) usual dietary intake; 4) body size and composition; and 4) n‐3 fatty acid status in relation to dietary intakes at the 2013 DNC World Final (London,UK). Mixed methods were used to evaluate the intervention and collect data from 22 of the 32 countries including: pre and post event questionnaires, anthropometric measurement, buccal cells (from saliva samples), observations and focus group interviews. Data are being analyzed in collaboration with the University of Surrey to explore the above objectives and to allow comparisons between countries and against WHO standards.

An extensive pilot study will be implemented in 2014 to include data collection in local DNC tournaments as well as at the DNC world final in Brazil (09/14).

Grant Funding Source: Supported by the Danone Institute International and the University of Surrey
The effect of dietary supplementation on the change in body composition of young Malian children with moderate acute malnutrition (620.2)
Authors: McDonald Christine , Ackatia Armah Robert , Doumbia Seydou , Brown Kenneth
Published: June 2021

Objective: To compare the effect of four dietary supplements for the treatment of moderate AM (MAM) on the change in body composition.

Methods: 289 Malian children age 6‐35 mths with non‐edematous MAM were randomized in clusters to receive 1 of 4 supplements, which provided 500 kcal/d for 12 wks: 1) Supplementary Plumpy (SP); 2) Corn Soy Blend ++ (CSB++); 3) Misola (MI); 4) Locally milled flours plus sugar, oil, and micronutrient powder (LMF). Body composition was assessed at baseline and 12 wks using deuterium oxide dilution and Fourier Transform Infrared Spectroscopy.

Results: At baseline, the mean ± SD age, mid‐upper arm circumference (MUAC), weight‐for‐length Z‐score (WLZ), body weight, total body water (TBW), fat‐mass (FM), and percent FM (%FM) across all subjects was 14.8 ± 7.2 months, 12.1± 0.5 cm, ‐2.20 ± 0.66, 7.03 ± 1.12 kg, 3.94 ± 0.76 kg, and 29.0 ± 6.32 %, respectively. At 12 wks, the adjusted increases of 1.23 kg in weight and 1.15 cm in MUAC were greatest in the SP group. FM increased by 0.35 kg, 0.29 kg, 0.25 kg, and 0.41 kg (p=0.02) among children in the SP, CSB++, MI, and LMF groups, respectively; however, the change in %FM did not differ between groups (p=0.13). Gains in MUAC, body weight, TBW, FM, and %FM were greater in children who recovered from MAM vs. those who did not recover (p<0.0001).

Conclusion: Body composition assessment provides additional insight into the type of tissue accrued during recovery from MAM.
Factors associated with stunting in Ethiopian children under 5: a comparison of DHS 2000, 2005 and 2011 (620.6)
Authors: Suri Devika , Griffiths Jeffrey , Ghosh Shibani
Published: June 2021

Background: 44% of Ethiopian children are stunted, negatively impacting physical and mental development. A conceptual hierarchical framework that categorizes risk factors into inherent, distal, intermediate and proximal has been used to examine risk factors associated with stunting.

Objective: Identify factors associated with stunting using a conceptual hierarchical framework and examine trends in these factors over time among children under 5 in Ethiopia.

Methods: Data from DHS (Demographic and Health Survey) 2000, 2005 and 2011 were analyzed. Step‐wise multivariate logistic regression was performed keeping only those factors with a significance of 0.1 or less.

Results: In 2011, factors associated with a significantly higher risk of stunting included being a boy, increased age, mother with no or only primary school education, lower SES, short birth interval, small birth size, small maternal stature, low maternal BMI and having a diarrhea episode in the last 2 weeks. Stunting has reduced significantly across the three surveys. There is only slight difference in risk factors over the years. In all three surveys, infants with small birth size are 1.5 times more likely to be stunted (p<0.05), diarrhea is associated with about 1.2‐1.3 times the risk of being stunted and for every cm increase in maternal stature, an infant is about 10% less likely to be stunted. In the 2011 survey, for every unit increase in BMI, the children are 5% less likely to be stunted.

Conclusions: Controlling for the effects mediated through education and wealth, birth interval, size at birth, maternal height, maternal BMI and diarrhea are still significant predictors of stunting in Ethiopian children.
Risk factors associated with stunting in Ethiopian children under 5 vary by wealth quintile (620.8)
Authors: Ghosh Shibani , Suri Devika , Griffiths Jeffrey
Published: June 2021

Background: Stunting can negatively impacting physical and mental development. Wealth is a strong predictor of stunting, but may be mediated by prenatal care, maternal health and feeding practices.

Objective: Identify factors associated with stunting in Ethiopian children under 5 across wealth quintiles.

Methods: Based on literature, a hierarchical risk framework was developed and the 2011 Demographic Health Survey data analyzed. Step‐wise multivariate logistic regressions were performed. Odds ratios were calculated.

Results: Children in the poorest quintile are more stunted compared to richest quintile (odds ratio: 1.82, p<0.0001), followed by poorer households (1.635, p=0.001), middle (1.592, p=0.001) and richer quintile (1.549, p=0.003). Older children are more likely to be stunted and maternal short stature is significant risk factor irrespective of wealth quintile. Continued breastfeeding in older infants and children (6‐12 months and older) is negatively associated with poorest, second poorest and the middle quintile, prevalence of diarrhea with the second poorest. Stunting was low in the richest but being a boy, less maternal education, smaller birth interval and birth size are associated with stunting in the wealthiest. Feeding practices were not a significant predictor in any quintile.

Conclusions: There is a linear relationship between stunting under five in Ethiopia and wealth quintile Factors associated with stunting vary by wealth. In sufficient variability in feeding practices data prevents understanding the link between infant feeding practices and stunting.
Is potato chips snacking associated with an increase of body weight in children? Results from the OBEY‐AD Study (621.1)
Authors: Gregori Dario , Vecchio Maria , Ballali Simonetta
Published: June 2021

Objective. In the last decades, the prevalence of obesity and overweight in children reaches the epidemic level. Poor eating habits, inadequate intake of vegetables, fruit, and eating too many high‐calorie snacks, play a role in childhood obesity. The aim of this study is to assess the relation between potato chips consumption and the increase of body weight in children aged 3‐11 years. Study design. The OBEY‐AD is a cross‐sectional study which has been conducted in 9 countries (Argentina, Brasil, France, Georgia, Germany, Great Britain, India, Italy and Mexico), enrolling 2635 children aged 3‐11 years. Children’s BMI CDC z‐scores have been computed for each child and categorized accordingly as Normal, Overweight or Obese and as Underweight. Parents have been asked about snacking habits in the family. A multivariable logistic model has been used to model risk of overweight or obesity in association with potato chips consumption. Results. Overall, 33% (857) of the children are snacking potato chips at least once per day, whereas 57% (1446) are not having access to them but rarely, varying from 51% in Brazil up to 80% in Argentina (p‐value < 0.001). Prevalence rates of obesity or overweight did not vary significantly according to potato chips consumption (p‐value = 0.19), ranging from 24% (164) in those who are snacking potato chips at least once per day up to 25% (361) in those who are snacking potato chips never or rarely. Non significance of the association persisted (p‐value 0.598) even after adjustment for major confounders (hours/week TV, physical activity, BMI father, BMI mother, number brothers or sisters, socio‐economic status, fruit portions/day, vegetables portions/day). Conclusions. The consumption of particular foods such as high energy dense foods is not responsible for prevalence rates of overweight and obesity if associated to a healthy lifestyle. The variety in food consumption and an adequate level of physical activity are two important factors associated with healthy habits.
Global trends in the childhood dual burden of malnutrition (621.2)
Authors: Tzioumis Emma , Adair Linda
Published: June 2021

The childhood dual burden of under‐ and overnutrition is a growing public health concern.

We used nationally representative, cross‐sectional, repeated Demographic and Health Surveys of children 0‐5y from 30 countries, 1990‐2011 (n=749,830). We estimated annualized rates of change (ARC) in stunting (height‐for‐age <‐2SD) and overweight (weight‐for‐height >2SD) based on WHO Child Growth Standards, accounting for survey design.

Comparing trends before and after 2000, stunting decreased in almost half the countries in both intervals, with larger rates of decline before 2000 (mean ACR = ‐0.71 vs. ‐0.54%/yr). Stunting trends switched direction in 2000 for 8 countries; for 5 countries, ARC decreased before 2000 then increased after (mean ARC = ‐0.93 vs. 0.79%/yr), and for 3 countries, ARC increased then decreased (mean ARC = 0.83 vs. ‐0.98%/yr).

Two countries had no appreciable change in overweight ARC, while 4 countries increased overweight in both intervals, with larger rates of increase after 2000 than before (mean ARC = 0.40 vs. 0.24%/yr). Eight switched trend direction; for 4 countries, ARC decreased before 2000 then increased after (mean ARC = ‐0.20 vs. 0.29%/yr), and for 4 countries, ARC increased then decreased (mean ARC = 0.43 vs. ‐0.25%/yr). Countries with greater decreases in stunting ARC tended to have greater increases in overweight ARC.

Overall, stunting has decreased and overweight has increased but trends vary, requiring deeper exploration.

Grant Funding Source: Supported by an educational grant from Wyeth Nutrition
Is breakfast associated with an increase of body weight in children? An international comparison based on the OBEY‐AD Study (621.4)
Authors: Gregori Dario , Vecchio Maria
Published: June 2021

Objective. Childhood obesity is nowadays a global problem affecting not only developed countries but also both low and middle‐income ones, particularly in urban settings. Breakfast is very important for the maintenance of an adequate intake of vitamins and minerals and for the improvement of diet quality and health in children and adolescents. The aim of this study is to assess whether skipping breakfast is associated with the increase of body weight in children aged 3‐11 years. Study design. The OBEY‐AD is a cross‐sectional study which has been conducted in 9 countries (Argentina, Brasil, France, Georgia, Germany, Great Britain, India, Italy and Mexico) enrolling 2635 children aged 3‐11 years, 50% females. Children’s BMI CDC z‐scores have been computed for each child and categorized accordingly as Normal, Overweight or Obese and as Underweight. Parents have been asked about breakfast habits in the family. A multivariable logistic model has been used to model risk of overweight or obesity in association with breakfast habits. Results. Overall, 70% of the children are having breakfast every day, consistently across the countries, varying from 64% in India up to 92% in France. About 14% of the children overall are not used to have breakfast in the morning. 29% of the children who are not taking breakfast were overweight or obese, as compared with 24% of those who are taking breakfast every day (p‐value =0.037). After adjustment for socio‐economic status of the family, BMI of the parents and physical activity, having breakfast every day resulted in a lowered risk of overweight of obesity as compared with no breakfast (OR 0.76, 95% C.I. 0.59‐0.97), consistently over all countries considered (p‐value for interaction terms 0.58). Conclusions. The data collected from the OBAY‐AD study indicate that skipping breakfast is associated with a higher risk of overweight of obesity. Promoting the breakfast consumption could be an important implication to prevent the weight gain in children.
Comparative study of bioactive peptides released from in vitro digestion of human milk and infant formulas (623.1)
Authors: Wada Yasuaki , Lönnerdal Bo
Published: June 2021

Human milk (HM), donor HM, and/or infant formulas (IFs) are the diets of most neonates. Bioactive peptides are known to be formed during gastrointestinal digestion of milk proteins, but the extent to which this occurs is not clear. HM, pasteurized HM (simulating donor HM), standard IF, and hypo‐allergenic IFs were subjected to in vitro digestion, followed by LC‐MS/MS analysis for identifying bioactive peptides. HM, where some peptides were present prior to digestion, released practically the same pattern of bioactive peptides with and without pasteurization, suggesting that provision of donor HM may be similar to breast‐feeding in terms of bioactive peptides, especially anti‐oxidative and ACE‐inhibitory peptides. Sequences of bioactive peptides were different between HM and standard IF, which may result in bioactivities with different intensity. Bioactive peptides formed from digestion of hypo‐allergenic IFs were less diverse than those from standard IF, indicating that industrial hydrolysis of cow’s milk protein for hypo‐allergenicity may impair the ‘encrypted’ bioactivities of the milk proteins. Further investigations in infants are needed to evaluate the bioactivities of the peptides.
Lactose: a milk‐specific carbohydrate enabling homeostatic regulation of glucose and insulin (623.12)
Authors: Innis Sheila , Novak Elizabeth
Published: June 2021

Lactose, a disaccharide of glucose and galactose, is uniquely present in mammalian milk. Human milk provides the infant with about 40% energy as lactose and 50% from fat. With 6‐7 g/dL lactose, the breast fed infant consumes high carbohydrate/kg body wgt, suggesting carbohydrate induced hepatic lipogenesis would be problematic with a high fat milk diet. However, galactose, unlike glucose is non‐insulinogenic and shows high hepatic clearance. We propose lactose in human milk confers unique metabolic advantage to the infant by delivering non‐insulinogenic carbohydrate which can be slowly metabolized in the liver to glucose or to support fatty acid oxidation. We determined insulin, glucose, triglyceride, free fatty acid and amino acid responses in 16 healthy adult men given in random order 650 mL carbohydrate‐free infant formula reconstituted to contain 50g lactose, glucose, sucrose or corn syrup solids. The milk formula was given 3 hr after a lactose and sucrose‐free meal, then again after 3 hr, to model the carbohydrate load and continuous feeding of breast‐fed infants. Blood was drawn every 15 min, and total and incremental area‐under‐curve change in insulin and glucose determined. Lactose gave a significantly lower rise in plasma insulin and glucose, in the first and particularly second 3 hr following intake, compared to glucose or corn syrup solids (P <0.001). Individual variability in triglyceride responses was high, with no difference due to carbohydrate in this 6 hr study. We show lactose enables maintenance of glucose and insulin equilibrium, avoiding high postprandial peaks achieved with glucose or corn syrups in milk fed at 3 hr intervals. We propose an important metabolic homeostatic role for lactose as carbohydrate source in human milk. Supported by Mead Johnson Nutrition.

Grant Funding Source: Mead Johnson Nutrition
Contribution of thiamin and riboflavin vitamers to total breast milk content (623.13)
Authors: Hampel Daniela , Shahab‐Ferdows Setareh , York Emily , Allen Lindsay
Published: June 2021

Thiamin (T) and riboflavin (R) are part of the B‐vitamin complex necessary for many metabolic processes. During lactation, nutrient needs increase to support maternal and infant requirements and inadequate supply has been described even in well‐nourished mothers. Both vitamins occur in several forms in breast milk (BM) contributing to its total content. We analyzed T, thiamin‐monophosphate (TMP), thiamin‐pyrophosphate (TPP), R, and flavin adenine dinucleotide (FAD) in existing BM samples from Malawian mothers collected at 2 and 24 wk. (n = 118). Concentrations were log‐transformed and means at 2/24wk were compared by paired t‐test (2wk: total T median: 154µg/L, TPP/TMP/T 5/88/7%; total R: 210µg/L, R/FAD 6/94%; 24wk: total T: 196µg/L, 2/77/21%; total R: 173µg/L, 8/92%). Free and total T sig. increased over time (p < 0.05), while TMP showed no change. TPP, a form previously not reported in BM, sig. decreased (p < 0.05). Thiamin transporters THTR1 and 2 present in the mammary gland might be responsible for preferred free T‐uptake rather than TMP/TPP, so free T may be driving total T increase. No change was found in free R, but FAD sig. decreased at 24 wk. Breast Cancer Resistance Protein (BCRP) actively transports R into BM while BCRP‐independent FAD transport has been suggested. The sig. lower levels of total R followed the trend found for FAD (p < 0.05); thus the coenzymatic form seems to mainly explain total R status.

Grant Funding Source: Bill & Melinda Gates Foundation (OPP53107)
Insulin, but not ghrelin, in human milk is related to maternal BMI and infant gain in fat mass (623.16)
Authors: Young Bridget , Patinkin Zachary , Reynolds Regina , Krebs Nancy
Published: June 2021

Excess infant weight and fat gain incur risk of later obesity. We investigated whether insulin or the orexigenic hormone, ghrelin, in human milk (HM) differed by maternal BMI and whether these hormones associated with infant adipose deposition.

26 normal weight (NW) and 23 overweight (OW) breastfeeding women provided fasted HM samples at 2‐wks (T1), 2‐mos (T2), and 4‐mos (T3) for analysis of insulin, ghrelin, and milk fat. Fasting maternal blood was collected at T3 for insulin and ghrelin. Infant body composition was measured (by PeaPodTM) at T1 and T3.

OW mothers exhibited higher insulin (p=0.04) and lower ghrelin (p<0.01) at T3 (n=18). HM insulin was positively associated with maternal pre‐pregnancy BMI at T1 (n=38; p<0.05) and T3 (n=18; p<0.05). Neither HM fat nor ghrelin differed between groups. Controlling for sex, infants of OW mothers weighed more at birth and remained larger until 1 mo (p<0.05). Neither infant %body fat nor fat mass (FM) differed between groups at T1 or T3, but infants of OW mothers had more fat‐free mass at both time points (p<0.03). Infant gain in FM (from T1 to T3) did not differ between groups. HM fat at T3 and insulin at T2 were predictive of infant gain in FM per day (p<0.03, R2=0.18, n=30; p<0.01, R2=0.52, n=17).

Differences between NW and OW mothers in circulating insulin, but not ghrelin were evident in HM. HM fat and insulin may play a role in early infant fat gain and contribute to later obesity risk.

Grant Funding Source: Supported by NIH T32 DK007658‐21, 5K24DK083772; Thrasher Research Fund; University of Colorado CCTSI
Impact of lutein and docosahexaenoic acid supplementation during lactation on plasma and breast milk (623.18)
Authors: Sherry Christina , Oliver Jeffery , Marriage Barbara
Published: June 2021

We assessed the effect of varying amounts of lutein and docosahexaenoic acid (DHA) on breast milk and plasma levels of these nutrients. Eighty‐eight lactating women 4‐6 weeks post‐partum were randomized in 3 groups: placebo, 6mg of lutein + 200mg DHA (low dose) or 12mg lutein + 400mg DHA (high dose). Breast milk and plasma lutein and DHA were assessed at the beginning and end of the study by HPLC for carotenoids and GC‐FID for fatty acids. Infant plasma lutein and DHA were assessed at the end of the study. Breast milk lutein and DHA were at most 4.5 and 2.2‐fold greater, respectively, as compared to placebo after supplementation; both increased in a dose dependent manner (R2=0.28 lutein; R2=0.20 DHA). Maternal plasma lutein and DHA had a similar fold change, 4.4 and 2.0, respectively, as compared to placebo. Infant plasma lutein was at most 4.2‐fold greater as compared to placebo. Breast milk lutein and DHA were correlated to maternal plasma levels (r=0.7747 lutein; r=0.4994, P<0.0001). Infant plasma lutein was also correlated to breast milk lutein (r=0.8347, P<0.0001) and maternal plasma lutein (r=0.8122, P<0.0001). There was no difference in average dietary intake of lutein or DHA among groups. Our results show that breast milk and plasma are responsive to increasing supplement doses of lutein and DHA and that the variation in these nutrients is also affected by individual variation and responsiveness to supplementation.

Grant Funding Source: Supported by Abbott Nutrition
Neurotrophin synthesis by mammary cells during lactation (623.19)
Authors: Hassiotou Foteini , Twigger Alecia‐Jane , Pundavela Jay , Roselli Severine , Hartmann Peter , Geddes Donna , Hondermarck Hubert
Published: June 2021

Neurotrophins are growth factors primarily described in the development of the nervous system. They are secreted by developing organs to attract nerve fibres, acting as molecular mediators for establishment of connections with the nervous system. Recent evidence demonstrates that mammary cells synthesize neurotrophins; however, variation in their expression is poorly understood. In this study, we examined expression of a panel of key neurotrophins and their receptors by mammary cells in the normal breast. Rare specimens of human resting and lactating breast tissue were stained for these genes. This demonstrated an upregulation of certain neurotrophins and associated receptors, such as pro‐NGF, in the lactating breast, and a differential expression of others, such as TrkA, between the myoepithelial and luminal layers. We next measured transcript levels in breastmilk cells from 20 lactating women. For some genes, such as TRKB1 and Sortilin, transcript levels were upregulated during lactation, while for others, such as NT‐3 and p75NTR, a marked downregulation was observed during lactation. These findings describe differential regulation of neurotrophin expression in the normal breast during different stages of development. The downregulation of some neurotrophins during lactation suggests a potential pathway of de‐sensitization of the breast, which may contribute to successful breastfeeding.
Preterm milk cytokines, severity of illness, and length of stay in very low‐birth‐weight infants (623.22)
Authors: Groer Maureen , Ashmeade Terri
Published: June 2021

Objectives The objectives were to characterize preterm milk cytokine, chemokine and growth factor (CCGF) levels and mother’s own milk (MOM) volumes across the first six weeks of a NICU stay in preterm infants weighing under 1500 Gms and to analyze relationships between milk immunobiology, volume and infant outcomes.

Method Seventy‐five mother infant dyads were enrolled. Mothers provided MOM and some infants also received donor milk or formula across the six weeks. Daily milk samples were pooled weekly. Milk CCGFs measured were EGF, IL‐10, IL‐4, IL‐8, IL‐6, MIP‐1α, TNFα, IP10, and MCP by multiplexing using the MagPix. Daily volume was recorded. Weekly stool samples were analyzed for fecal calprotectin levels. Infant severity of illness was measured each week. Length of stay (LOS) and other health outcomes were measured.

Results All cytokines decreased across time from highest levels at week 1. Chemokines declined less markedly. Milk from mothers of smaller infant had higher EGF (p<.001). IL4 ( p<.009 ), IL‐8 (p<.009 ) were inversely correlated with illness scores , while MIP1 α (p<.005)and IL8 (p<.001)were positively correlated. Several cytokines also correlated with LOS. FC increased over time and was correlated with amount of MOM(p<.005) but not with any CCGF.

Conclusions MOM CCGF may in part be regulated by infant and developmental signals. CCGF are important molecules that promote growth, immune development and gastrointestinal maturity.

Grant Funding Source: Supported by NIH ( 5R21NR013094‐02 )
Carotenoids and flavonoids in human milk: longitudinal patterns from China, Mexico, and the USA (623.25)
Authors: Lipkie Tristan , Song Brian , Probst Matt , Morrow Ardythe , Peng Yongmei , Guerrero Maria , Ruiz‐Palacios Guillermo , McMahon Robert , Jouni Zeina , Ferruzzi Mario
Published: June 2021

Emerging evidence indicates that particular phytochemicals may have a role in infant nutrition and development, yet data on carotenoid and flavonoid content of human milk remains sparse. Milk was longitudinally collected at 2, 4, 13, and 26 weeks postpartum from twenty mothers each in China, Mexico, and the USA to determine the variation in composition by donor, lactation stage, and country. Maternal and neonatal plasma was analyzed for carotenoids from the USA cohort at 4 weeks postpartum. Donor strongly predicted (p<0.01) total carotenoid content (mean ± SEM = 17.1 ± 10.2 nmol/g lipid) and total flavonoid content (103.5 ± 96.1 nmol/L). With increasing weeks postpartum, the content of provitamin A carotenoids (nmol/g lipid) increased (p<0.05 except for alpha‐carotene), but other phytochemicals remained unchanged. Country of origin also influenced composition: Total carotenoids and lutein content were greatest, while lycopene was lowest, in milk from China; and the individual flavonoid aglycone epicatechin gallate had the highest concentration in milk from Mexico (p<0.05). Lutein, β‐cryptoxanthin, and β‐carotene were correlated (p<0.05) between maternal plasma, milk, and neonatal plasma, but lycopene levels of neonatal plasma did not depend on milk content. Anthocyanins were not detected in human milk samples. These results expand our knowledge of phytochemical composition of human milk globally.

Grant Funding Source: Supported by Mead Johnson Nutrition, USDA National Needs Program and NICHD HD13021.
Extraction of RNA and microRNA from human milk (623.3)
Authors: Hassiotou Foteini , Alsaweed Mohammed , Hepworth Anna , Lefevre Christophe , Hartmann Peter , Geddes Donna
Published: June 2021

Human milk contains both free and encapsulated RNA and microRNA in its cell, lipid and skim milk fractions. Recently, the microRNA content of human milk has attracted much attention due to its high variability and the presence of microRNAs with known immunomodulatory functions. However, optimization of the extraction of RNA and microRNA from different fractions of human milk, which is a prerequisite for investigating the functions of these milk molecules, has not been carried out. In this study, we compared eight commercially available kits for their efficacy in extracting RNA and microRNA from the three fractions of human milk. The highest quantities of both RNA and microRNA were recorded for the cell and lipid fractions, and the lowest for skim milk. The most efficient method for RNA and microRNA extraction was the column‐based phenol‐free method, and the least efficient the phenol‐based guanidine method. Interestingly, some kits were more efficient in extracting high quantities of RNA or microRNA, whilst others performed better in extracting high‐purity RNA or microRNA. This now provides guidance for extracting RNA and microRNA from different breastmilk fractions allowing a more comprehensive profiling of these breastmilk molecules and their functions for the breastfed infant.
Optimization of anti‐glycation effect of L‐carnitine, vitamin B6 and dl‐α‐tocopheryl acetate in infant formula model system using response surface methodology (623.5)
Authors: Jung Hye‐Lim , Nam Mi‐Hyun , Hong Chung‐Oui , Oh Jun‐Gu , Seol Hye‐Min , Kim Ji‐Yeon , Oh JinHwa , Kim Young Ki , Choi You Young , Kwon Jung Il , Lee Kwang‐Won
Published: June 2021

The Maillard reaction is a chemical reaction between amino group and carbonyl group during food processing. In the case of milk, lactose reacts with the free amino acid side chain of milk protein.Infant formulas (IF) are milk‐based products and usually heat‐treated such as sterilization, spray‐dry to ensure microbiological safety and extend the shelf‐life period. As a consequence of thermal treatment, IF forms amadori products which then form advanced glycation end products (AGEs). IF may have more AGEs than breast milk. As a result, formula‐fed babies are being exposed to high levels of AGEs. In this study, we optimized the anti‐glycation effect of L‐carnitine, vitamin B6 and dl‐α‐tocopheryl acetate in IF model system using RSM.The model system was prepared by mixing sodium caseinate (3 mg/mL) and lactose (8.4 mg/mL) with and without antioxidants at 100°C for 30 min. The treatment conditions that were based on the central composite design with independent variables and the responses were monitored by fluorescence intensity and HMF content.The optimum levels of antioxidants for anti‐glycation in a model system, i.e.L‐carnitine, vitamin B6 and dl‐α‐tocopheryl acetate, were 8.05 μM, 12.37 μM, 18.4 μM for fluorescence intensity(63%), 1.6 μM, 18.4 μM, 18.4 μM for HMF(65%). Under these conditions, the experimental results were 90% for fluorescence intensity and 89% for HMF.
A black box illuminated: specific detection and quantification of vitamin D3 in small volume human milk samples using nanoLC‐ESI/MS/MS (623.8)
Authors: Maria Sarah , McMahon Robert , Davidson Barbara , Morrow Ardythe , Zhang Qiang
Published: June 2021

Breastfeeding infants are at particular risk for vitamin D deficiency with human milk as their primary source of vitamin D. Serum 25‐OH‐D is typically used to characterize maternal and infant vitamin D deficiency. However, direct measurement of vitamin D in human milk is critical to illuminate the black box representing maternal vitamin D contribution to the infant during feeding. Here we have developed a sensitive and specific method to quantitate low femtomolar levels of vitamin D3, a common form in human milk, from an individual donor using 1 mL of human milk. The method combines initial saponification of human milk with liquid‐liquid extraction, followed by UPLC clean‐up, derivatization, and nanoLC‐MS/MS analysis. Deuterated D3 was used as internal standard. Full product ion spectra with accurate masses (±20 ppm) were obtained where MRM transitions of m/z 560.385 ‐> 298.119 and 563.404 ‐> 301.137 were used for quantification. Six milk samples from 3 mothers at two lactational stages, 2 weeks and 2 months, were analysed to assess method performance and give initial insight into vitamin D3 over lactation. Vitamin D3 concentrations increased from 0.09 ‐ 2.1 pmole/mL in 2‐week milk to 1.3 ‐ 2.7 pmole/mL in 2‐month milk. Milk from two of the mothers showed an approximate 10‐fold increase over the 6 weeks between sampling, while the third mother had higher initial values of D3 with a modest 30% increase between 2 weeks and 2 months.
Intervention design for increasing fruits and veggies among low‐income pregnant Latinas (624.12)
Authors: Hromi‐Fiedler Amber , Chapman Donna , Segura‐Pérez Sofia , Damio Grace , Bermúdez‐Millán Angela , Clark Pamela , Pérez‐Escamilla Rafael
Published: June 2021

The primary study objective is to identify a culturally appropriate intervention to increase fruit and vegetable (F&V) intake among low‐income pregnant Latinas. One focus group and 2 small group discussions have been conducted with: (1) Latina prenatal care staff members from a local community based organization (N=5); (2) younger and more acculturated pregnant Latinas (N=2); (3) older and less acculturated pregnant Latinas (N=3). Group discussions lasted from 116 to 165 min. Preliminary content analysis indicates consensus that pregnancy is a “teachable moment” where maternal eating patterns can be influenced due to the benefit it offers the offspring. Also, nutrition education sessions and cooking/taste testing demonstrations (with recipes) should be vital intervention components, thus teaching participants to prepare healthy, tasty dishes. The first two groups favored both group and individual education delivered by community health educators, while those in the latter group favored group education only. Eliciting individual motivation and determination to change were cited as key factors for intervention success. Staff participants felt improving physical and economic access to F&Vs also needed to be a key intervention component, citing various methods including using existing resources (i.e. produce mobile vending units), encouraging community gardens, or providing F&Vs through local NGOs. Preliminary findings suggest that the social‐ecological framework should guide the final intervention design.

Grant Funding Source: Supported by NIH‐NINR (Grant #: 1R21NR013970)
The effect of acculturation on Latina mothers’ food choices and body weight ideals for their children (624.13)
Authors: Chavoor Tracie , Papathakis Peggy , Voorheis Grace , Harrison Kelly
Published: June 2021

Objective: Focus groups of low income Latina mothers were conducted to identify reasons mothers make family food choices and to understand perceptions of body sizes and if these differed by acculturation.

Results: Eight groups were held (n=30). In four groups of bi and low acculturated mothers, eight similar themes and four different themes were identified between bi and low acculturated groups. Similar themes included: challenges cooking traditional and healthy foods due to family preferences, looking to doctors to categorize their child’s weight and lower acculturated mothers have less awareness of their child’s weight than high acculturated ones. Low acculturated groups mentioned growing up with low food availability that led them to feed their children more liberally. Bi acculturated groups mentioned not believing the doctor when told their child was overweight.

Conclusions: Latina mothers encounter barriers when preparing traditional foods for their children, especially considering their children’s preferences for American foods. Dietary acculturation can lead to unhealthy eating patterns. Doctors have an important role in correcting misinformation on appropriate body size however doctors frequently fail to bring up weight during visits. As the women acculturate they may become more aware of weight due to the western emphasis on body image.

Grant Funding Source: Supported by California State WIC and the Ag Research Initiative
Association between socioeconomic household level and z‐score of BMI in children: results of a longitudinal study (624.14)
Authors: Liria| Maria , Penny Mary , López‐Ridaura Ruy , Romero‐Martínez Martín , Caballero Benjamín , Colchero‐Aragonés Arantxa
Published: June 2021

Improvements in socioeconomic conditions in countries in transition tend to be accompanied by increases in the prevalence of overweight and obesity. Peru is experiencing important macroeconomic changes that are modifying living conditions of households, which may have affected the prevalence of obesity. To estimate the effect of socioeconomic status on children´s weight, we used data of Niños del Milenio, part of the Young Lives Study, a longitudinal study of childhood poverty representing the poorest 95% of districts in Peru. In 2002, 2052 children 6‐17 months were enrolled, visited and measured again in 2006 and 2010. We used mixed models to evaluate the association between BMI and household socioeconomic level, food expenditures, and maternal education. The BMI z‐score was significantly positively associated with household income terciles and maternal education level. These associations were strongest in the third round, and between the third and first income terciles (+0.31 + 0.05, p<0.000), and between level of maternal education (high school vs. elementary/no illiterate: +0.39 + 0.07, p<0.000). BMI z‐score in round 3 was higher in households that spent more on ultra‐processed food (third vs. first terciles: +0.24 + 0.05, p<0.000) and on foods eaten away from home (spent/no spent: +0.11 + 0.04, p=0.016). This study reinforces the importance of continued vigilance and policies to increase the availability and consumption of healthier foods to reduce childhood overweight and obesity.