bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of dietary patterns in very young children: food sources of energy (252.3)
Authors: Reidy Kathleen , Deming Denise , Fox Mary Kay , Briefel Ronette
Published: June 2021

Data from the Feeding Infants and Toddlers Study (FITS) 2008, a national survey of young children, were analyzed to understand the development of dietary patterns in infants, toddlers and preschoolers, focusing on food sources of energy and key nutrients. Twenty four hour dietary recalls were conducted by telephone with parents or primary caregivers of 3200 children age 0‐4 years. The diet transitions during this period from an all milk diet, with milks representing 98% en in the youngest age group ( 0‐3 months) to 15‐17% en by ages 2‐4 years, when children have transitioned to the family table. Data show that problematic dietary patterns, that are quite high in sweets (15% en) and grains (32% en) and low in fruits (7% en) and vegetables (4% en) develop rapidly starting in infancy and are fairly set as early as age 2. Further analysis shows that discretionary calories, energy from solid fats and added sugars, in 2‐4 year olds is 408 calories, more than one third of total energy intake. With over 10% of children ages 2‐5 already obese, it is critically important to lay the foundation for healthful dietary patterns very early in childhood, when eating habits and food preferences are being formed.

Grant Funding Source: Supported by Nestle Infant Nutrition
Antenatal multiple micronutrient supplementation and growth in the first two years of life and cognitive function at 24 months in rural Bangladesh (256.5)
Authors: Christian Parul , Shamim Abu , Shaikh Saijuddin , Ali Hasmot , Mehra Sucheta , Lee Wu , Labrique Alain , Schulze Kerry , Klemm Rolf , West Keith
Published: June 2021

In a cluster‐randomized, controlled trial in rural Bangladesh, antenatal multiple micronutrient (MM) vs. iron‐folic acid (IFA) supplementation enhanced birth weight and length. We assessed the effects of the intervention on growth at 1, 3, 6, 12 and 24 mo of age and cognitive function using Bayley‐III at 24 mo. Children were born with low mean (SD) length for age Z‐score (LAZ) of ‐1.58 (1.20) in the MM and ‐1.69 (1.26) in the IFA group (p<0.001). Linear growth improved over the first 6 months in both groups. MM increased LAZ by mean (SE) 0.06 (0.01), at both 1 and 3 mo of age compared to IFA after adjusting for birth LAZ and design effect (both p<0.001). Stunting prevalence was lower at 1 mo (32.2 vs. 36.0%, RR=0.95, 95% CI:0.92, 0.98) and at 3 mo (24.5 vs. 29.0%, RR=0.91, 95%CI:0.88, 0.94) in the MM vs. IFA group, after adjusting for stunting at birth. The difference between groups was attenuated and not significant by 6 mo and absent by 12 and 24 mo of age, at which time stunting prevalance was 50%. In a substudy (n=750), there was no treatment effect on composite scores of cognition, language, and motor performance or behavior at 24 mo. MM supplementation improved postnatal linear growth beyond birth, but after supplement use had ended at 3 mo postpartum, and around the age of introduction of complementary foods at 6 months, the benefit on growth was no longer apparent, suggesting that infections and inadequate breastfeeding and complementary feeding practices have a strong influence on growth beyond 6 mo in this rural South Asian context.

Grant Funding Source: Supported by the Bill & Melinda Gates Foundation Grant 614
Maternal education modifies the association between food insecurity and risk of short IPI among low income women in Massachusetts (268.5)
Authors: Metallinos‐Katsaras Elizabeth , Siu Elizabeth , Colchamiro Rachel
Published: June 2021

Periconceptional nutrition’s importance has been established through a large body of research, showing adverse effects of poor periconceptional nutritional status on a variety of health outcomes. This study examined the association between food security status during the Inter‐pregnancy interval (IPI) and risk of short IPI among low income women participating in MA WIC (2001‐2009). Women who were on WIC for both 1st and 2nd pregnancies, had singleton full‐term (38‐42 wks) live births, and had complete data on ethnicity, education, age, household (HH) size, pre‐pregnancy weight before 2nd pregnancy, 1st infant’s breastfeeding duration and HH food security status from the 2nd pregnancy were included in these analyses (n=10,625 mothers). IPI= the estimated date of conception for the 2nd pregnancy ‐ the birth date of the first child. Logistic regression was used to examine the association between food security and short IPI (< 12 months), controlling for the aforementioned covariates. Sample characteristics were: mean age of 22.6 years (SD=5.1 yrs), 54.6% non‐white, 23.4% with food insecurity (18.5% low food security (LFS) and 4.9% very low food security (VLFS)), and 28.5% with short IPI. HH food insecurity was associated with a higher risk of short IPI; this varied by maternal education. Among mothers with < 12 years of education, those with VLFS were 56% more likely [OR=1.56, 95%CI=1.1‐2.1] to have short IPI compared to food secure mothers. Those with LFS tended toward increased risk for short IPI [OR=1.20, 95%CI=1.0‐1.4]. Among mothers with > 12 years of education, those with LFS were 28% more likely [OR=1.28, 95%CI=1.0‐1.63] to have short IPI than food secure mothers; there was no association with VLFS risk [OR=1.39, 95%CI=0.9‐2.2]. Among mothers with 12 years of education neither LFS [OR=1.0, 95% CI=0.9‐1.2] nor VLFS [OR=0.8, 95%CI=0.6‐1.1] were associated with short IPI. Food insecurity increased the risk of short IPI in this low income population but the effect varied by maternal education.

Grant Funding Source: Supported by UCLA/USDA
Infliuence of age on the absorption, metabolism an excretion of cocoa flavanols (270.4)
Authors: Rodriguez‐Mateos Ana , Cifuentes‐Gomez Tania , Ottaviani Javier , Schroeter Hagen , Heiss Christian , Spencer Jeremy
Published: June 2021

Accumulating evidence from dietary intervention studies suggest that regular consumption of foods and beverages rich in flavanols may have cardiovascular benefits. However, such biological effects are dependent on the bioavailability of flavanols, and, as such, individual variations in absorption, metabolism and excretion are highly relevant. The aim of this study was to investigate whether or not the absorption, metabolism an excretion of cocoa flavanols is age‐dependent. A 3‐armed randomized, cross‐over intervention study was performed in 40 healthy, caucasian men aged 18‐35 or 65‐80 years old. The subjects received either 5.3 or 10.7 mg CF/Kg body weight (BW); 1 gram of acetaminophen was used as a control to compare differences in metabolism. Plasma and urine samples were collected over 24 hours post‐consumption, and were analysed by HPLC with UV, fluorescence and electrochemical detection. Our data demonstrate that the intra‐ and inter‐individual variability of flavanol absorption is relatively low, and while small differences in the metabolism and catabolism of flavanols were identified as a function of age, in general, flavanols were absorbed, metabolised and excreted in a similar fashion, thus supporting future efforts to establish population‐level cocoa flavanol intake recommendations.

Grant Funding Source: FP7 grant of the European Union entitled FLAVIOLA (FP7‐KBBE‐2008‐2B).
microRNAs in bovine milk are bioavailable in healthy adults and downregulate reporter gene activity in human kidney HEK‐293 cell cultures (271.4)
Authors: Baier Scott , Zempleni Janos
Published: June 2021

MicroRNAs (miRNA) repress gene expression at the level of transcription and translation. MiRNA are stable and evolutionary conserved. We tested the novel hypothesis that dietary miRNA in bovine milk are bioavailable and affect human gene expression. Milk and miR‐29b were chosen as models because of the large amounts of milk consumed in the U.S., the abundance of miR‐29b in milk, and the role of miR‐29b in bone health. We tested our hypothesis in milk feeding studies in adults using a randomized crossover design, and a reporter gene assay in HEK‐293 cell cultures. Plasma levels of miR‐29b peaked 3 h after milk consumption to 247% above baseline levels (as per qRT‐PCR; P=0.03; n=6; t‐test), consistent with absorption occurring in the upper small intestine. Levels of miR‐200c and miR‐150 (neg. control) in milk are 800% and <1%, respectively, that of miR‐29b. The peak plasma level of miR‐200c increased 383% above baseline, whereas miR‐150 levels did not change, consistent with a dose‐response relationship and assay specificity. Culturing HEK‐293 cells with miRNA from milk decreased the activity of a miR‐200c reporter gene by 24% compared with vehicle controls. We conclude that milk‐borne miRNA alter the expression of human genes, creating a pattern conducive to bone health. Our findings are significant in infant nutrition (miRNA content in formulas vs. breast milk) and the nutrition of postmenopausal women (osteoporosis).

Grant Funding Source: Supported by ARD Hatch and NIH.
Hindlimb heating increases vascular access of large molecules to murine tibial growth plates measured by in vivo multiphoton imaging (342.3)
Authors: Serrat Maria , Williams Rebecca
Published: June 2021

Advances in understanding the molecular regulation of linear growth have led to development of novel drug therapies for growth plate disorders. An unmet challenge is delivering agents to avascular cartilage plates. Dense matrix and lack of penetrating blood vessels create a semi‐permeable vascular‐cartilage “barrier,” which hinders molecular transport. We employed a hindlimb heating model to manipulate bone circulation in 5‐week‐old female mice (N=22). We used in vivo multiphoton microscopy to quantify temperature‐enhanced delivery of large molecules into tibial growth plates. We tested the hypothesis that increasing hindlimb temperature from 22C to 34C increases vascular access of large systemic molecules, modeled using 10‐, 40‐, and 70 kDa dextrans that approximate sizes of physiological regulators. Vascular access was quantified by vessel diameter, velocity, and dextran leakage from vessels and accumulation in growth plates. Growth plate entry of 10 kDa dextrans increased over 150% at 34C. Entry of 40‐ and 70 kDa dextrans increased < 50%, suggesting size‐dependence. Velocity and vessel diameter increased 118% and 31%, respectively, at 34C. Results demonstrate that heat enhances vascular carrying capacity and bioavailability of large molecules around growth plates, suggesting that temperature could be a noninvasive way to enhance therapeutic delivery to impaired growth plates of children.

Grant Funding Source: Supported by NSF MRI‐R2 0959012 and 0929997, WV‐NASA, and UK‐CCTS (NIH UL1TR000117)
Associations between change in DASH diet scores and CVD risk factors in the PREMIER Trial (369.1)
Authors: Beasley Jeannette , Viswanathan Shankar , Wylie‐Rosett Judith
Published: June 2021

OBJECTIVE: To measure associations between changes in the Dietary Approaches to Stop Hypertension (DASH) dietary indices and changes in blood pressure (BP), weight, and waist circumference (CVD risk factors) in PREMIER, a randomized, controlled trial of behavioral intervention for hypertension with and without the DASH dietary pattern.

METHODS: DASH diet scores were derived based upon nutrient (9 nutrients, DASH_Nutrient) and food‐based (8 food groups, DASH_Food) targets using two 24‐h recalls administered at baseline, 6 months, and 18 months. Generalized estimating equations (GEE) were used to assess associations between CVD risk factors per SD change in the two DASH indices after accounting for confounders and randomization group.

RESULTS: At baseline (n=807), lower DASH scores were associated with higher BMI, African‐American race, and younger age for both indices. Spearman correlations between the indices were 0.36. Mean DASH scores at baseline and 18 months were 2.7 (SD=1.4) and 3.7 (SD 1.4) for DASH_Nutrient (range 0 to 9) and 36.2 (SD=10.5) and 40.0 (SD 11.8) for DASH_Food (range 0‐80). Each SD increase in DASH_Nutrient was associated with a ‐1.26 (95% CI: ‐1.91 to ‐0.61) mmHg decrease in systolic BP versus a ‐0.87 (95% CI: ‐1.44 to ‐0.30) mmHg per SD change in DASH_Food. Each SD increase in DASH_Nutrient score was associated with a ‐0.50 (‐0.95 to ‐0.06) unit decrease in diastolic BP. Changes in the DASH_Food score were not significantly associated with changes in diastolic BP.

INTERPRETATION: The DASH dietary pattern defined by nutrient, rather than food, intake is more closely associated with reduction in CVD risk factors.

Table. Longitudinal associations (Mean (95% CI)) between changes from baseline in DASH Diet Scores and CVD risk factors

CVD Risk Factor
DASH_Nutrient (derived based on Mellenâ€™s DASH Index), per SD
DASH_Food (derived based on Guntherâ€™s DASH Index), per SD

Systolic Blood Pressure, mmHg
‐1.26 (‐1.91 to ‐0.61)
‐0.87 (‐1.44 to ‐0.30)

Diastolic Blood Pressure, mmHg
‐0.50 (‐0.95 to ‐0.06)
‐0.32 (‐0.75 to 0.11)

Weight, lb
‐1.94 (‐2.80 to ‐1.17)
‐1.10 (‐1.71 to ‐0.49)

Waist Circumference, cm
‐0.89 (‐1.29 to ‐0.48)
‐0.75 (‐1.10 to ‐0.40)

GEE models with unstructured correlation matrix adjusted for baseline CVD risk factor, baseline DASH score, sex, race, age, education, smoking (current, former, never), physical activity, energy intake, BMI, and randomization assignment.
Effects of high‐protein weight loss diets on fat‐free mass changes in older adults: a systematic review (371.5)
Authors: Kim Jung Eun , Sands Laura , Slebodnik Mary , O’Connor Lauren , Campbell Wayne
Published: June 2021

With advancing age, many adults experience increased body weight (BW) and fat mass (FM) but decreased fat‐free mass (FFM). Purposeful moderate dietary energy restriction (ER) (500‐750 kcal/d E deficits) reduces BW and FM, but also FFM. High protein (HP) vs. normal protein (NP) intake during ER may more effectively retain FFM, but this issue requires systematic evaluation in older adults. We conducted a systematic review of randomized control trials (RCT) to assess the effects of protein intake on ER‐induced changes in FFM in adults mean age 50+ years. Eighteen RCT were systematically evaluated with HP defined as either 1) > 25% of the total E from protein; or 2) > 1 g protein/(kg[[Unsupported Character ‐ Symbol Font ř]]d). The median protein intakes of the HP and NP groups were 30 and 18 % of the total E intake (ranges: 25‐40 and 15‐20), respectively, and 1.53 and 0.87 g protein/(kg[[Unsupported Character ‐ Symbol Font ř]]d) (ranges: 1.04‐1.89 and 0.66‐0.99), respectively. With dietary protein expressed as % of E intake, fewer HP vs. NP groups lost 蠅 30% of BW as FFM (20 vs. 44 % of groups) and more HP vs. NP groups lost < 20 % of BW as FFM (40 vs. 17 % of groups). Similarly, using g protein/(kg[[Unsupported Character ‐ Symbol Font ř]]d), fewer HP vs. NP groups lost 蠅 30% of BW as FFM (19 vs. 44 % of groups) and more HP vs. NP groups lost < 20 % of BW as FFM (44 vs. 12 % of groups). These findings indicate that old adults can more effectively retain FFM during weight loss when they consume a high‐protein diet.

Grant Funding Source: Support by Purdue Univ Ingest Behav Res Ctr
Caregivers’ perceptions about picky eating: associations with texture acceptance and food intake (379.3)
Authors: van der Horst Klazine , Eldridge Alison , Deming Denise , Reidy Kathleen
Published: June 2021

Picky‐eating children accept only a limited number of foods, are unwilling to try new foods, have strong food preferences (likes/dislikes), and more often require special preparation of foods. Appropriate texture introduction is important and might impact food acceptance and picky eating, but not much is known about texture acceptance in picky eating infants and toddlers. In this study, data from the 2008 Feeding Infants and Toddlers Study (FITS) was used to examine associations between picky eating and food group consumption, intake of various types of vegetables, and texture acceptance in infants and toddlers between 4 and 48 months. The percentage of children identified as very picky eaters by their caregivers increased from 3.4% in 6‐12 month olds to 15.6% in 36‐48 months old children. Between 36 and 48 months old, 57% of parents indicated that their child is a very or somewhat picky eater. At the same time, caregivers perceived 17.8% of infants between 0 and 6 months to be resistant of food textures, which might be normal in a phase of introducing first solids. Surprisingly, parents report increasing prevalence’s of children’s resistance to food textures, with a prevalence of 36% for children between 2 and 4 years old. Shifts in the intake of types of vegetables, e.g. how picky eaters shift from baby food vegetables to non‐baby foods, and associations with texture acceptance will be presented.

Grant Funding Source: Funded by Nestlé Nutrition
Osteopontin supplementation of formula shifts the peripheral blood mononuclear cell transcriptome to be more similar to breastfed infants (38.3)
Authors: Donovan Sharon , Monaco Marcia , Drnevich Jenny , Lönnerdal Bo , Kvistgaard Anne , Peng Yong‐mei
Published: June 2021

OPN is a key modulator in cell‐mediated immune and anti‐inflammatory responses that is present in breast milk, but not infant formula. A randomized clinical trial was conducted to study the impact of bovine OPN in formula on infant PBMC gene expression. Mothers chose to either breast‐(BF) or formula‐feed their infant. Formula‐fed infants received: formula (FF), formula with 65 mg/L (F65) or 130 mg/L (F130) OPN. Blood samples were collected 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 modules (4066 probe sets) identified patterns where FF65 infants were similar to BF and different from FF and F130 across time. Functional analysis was performed with MetaCore. Pathways with higher expression in BF and F65 focused on cell proliferation and cell‐cell adhesion, supporting increased production and maturation of immune cells. In contrast, PBMC from FF and F130 infants expressed more genes related to immunoglobulin synthesis and receptors, including a gene associated with risk of childhood allergy. Thus, supplementing infant formula with OPN shifted PBMC gene expression to be more similar to BF and may support improved immune development.

Grant Funding Source: Supported by: Arla Foods Ingredients and Biostime
Gender differences in participation in a mHealth intervention to promote lifestyle changes in Latin America (380.8)
Authors: Kanter Rebecca , Ramirez‐Zea Manuel , Martinez Homero
Published: June 2021

Background: In public health, often men are harder to reach than women. Mobile health (mHealth) interventions offer a solution. Quantifying how effective a mHealth intervention is in reaching both genders is critical for progress in this field.

Objective: To explore if a mHealth intervention reaches both genders equally, identifying perceived barriers and potential solutions.

Methods: A quantitative and qualitative survey was given to a random sub‐sample of subjects who participated in a 1 y mHealth intervention to promote lifestyle change (monthly phone calls and weekly SMS) in Argentina, Guatemala, and Peru (n = 20‐40 per country). Chi‐squared tests were used to determine gender differences in active participation in the intervention. All qualitative information was thematically coded and analyzed in Dedoose.

Results: The perceived active participation in the intervention did not vary significantly (p<0.05) by gender. More men than women found the calls to promote better dialogue to facilitate lifestyle change. Men and women listed different barriers to not attaining monthly goals about diet and physical activity. Men had more suggestions for improving the intervention.

Conclusions: A mHealth intervention had equal reach regarding gender, which is important for public health programs. Lifestyle changes are hard, but mHealth methods can facilitate these changes in poor urban settings in Latin America.

Grant Funding Source: Supported by NHLBI and UHG
Canned bean popularity varies by acculturation among low income Latinas (393.6)
Authors: Winham Donna , Thompson Sharon , Armstrong Florian Traci
Published: June 2021

Canned dried beans such as pinto, black, navy, and kidney were recently added as WIC food package options. With reduced preparation time and a long storage life, canned beans provide a nutritious non‐fat vegetable source of protein, fiber, folate, and other micronutrient options to busy families with limited resources. Survey data regarding attitudes toward consumption and perceptions of canned beans were collected from 443 low income women aged 18‐65 enrolled in WIC, EFNEP, and a county unemployment center. Seventy‐two percent self‐identified as Hispanic and 53% were non‐US born. Using the Bidimensional Acculturation Scale (BAS), 38% were Hispanic‐dominant (SPAN), 23% bicultural (BI), and 39% English‐dominant (ENG). There were significant differences in attitudes and perceptions of canned beans by acculturation as measured by the BAS. Only 23% of SPAN women purchased canned beans in contrast to 53% of BI, and 76% of ENG women. For Likert scale questions on canned bean attributes, more SPAN women agreed than their BI or ENG peers that canned beans: do not taste good (50%, 27% BI, 19% ENG), their family will not eat them (42%, 20% BI, 14% ENG), are not healthy (26%, 13% BI, 5% ENG), and contain preservatives (64%, 42% BI, 27% ENG). These attitudes and misperceptions reduce the policy effectiveness of including canned beans as well as the potential time savings in food preparation. Health education with low income Latinas should include culturally appropriate dialogue to increase or maintain bean consumption in this vulnerable population.
A multi‐center assessment of the nutritional quality of hospital patient menus (393.7)
Authors: Arcand JoAnne , Fraser Jaclyn , Wilkinson Lori , Trang Susan , Steckham Katherine , Fletcher Heather , Oliphant Heather , L'Abbe Mary , Tzianetas Roula
Published: June 2021

In Canada, there are no widely accepted standards for hospital menu planning. The objective of this study was to evaluate the quality of nutrients and foods served on hospital patient menus. At 3 acute care hospitals in Ontario, Canada (Nov‐Aug 2011), 84 standard menus and 2234 consecutive patient‐selected menus were evaluated in regular and diabetic diets, and 3000 mg and 2000 mg sodium restricted diets. Comparisons were made against the Dietary Reference Intakes (DRI) and Canada’s Food Guide. Energy levels ranged from 1281 ‐ 3007 kcal and 45% of standard menus had < 1600 kcal. Protein ranged from 49 ‐ 159 g and 30% of standard menus had < 60 g. The standard regular menu, the most commonly prescribed, had 1673 ± 362 kcal and 63 ± 9 g protein. Energy and protein levels were highest in diabetic menus. All standard regular and diabetic menus fell within the Acceptable Macronutrient Distribution Range. The proportion of regular standard menus meeting the DRIs were 0% for calcium, sodium, and fibre; 50% for Vitamin C; and 86% for iron. 100% of sodium‐restricted menus fell below the DRI for calcium. Most menus met Milk & Alternatives recommendations, though only 27% met Vegetables and Fruit, 11% met Grain Products, and 8% met Meat & Alternatives recommended servings. These data show that patient menus did not consistently meet recommendations for macronutrient and vitamin and minerals or for the number of Canada’s Food Guide servings, which may contribute to malnutrition. This data supports the need for policies guiding food procurement and menu planning in hospitals.
Effects of prolonged calorie restriction on inflammation and immune function: a randomized controlled trial in non‐obese humans (40.4)
Authors: Meydani Simin , Das Sai , Piper Carl , Lewis Michael , Dixit Vishwadeep , Gupta Alok , Villareal Dennis , Klein Samuel , Bhapkar Manjushri , Huang Megan , Fuss Paul , Roberts Susan , Holloszy John , Fontana Luigi
Published: June 2021

Calorie restriction (CR) is shown to improve inflammatory and immune responses and extend life in animals; however, the effect of prolonged CR in humans has not been studied. CALERIE is a multi‐center randomized controlled trial, which evaluated the impact of 2 y of 25% CR on key biological functions. As part of the CALERIE we determined the impact of CR on immune and INFL markers of 218 healthy adults aged 21‐50 y with BMI of 22‐ 29 kg/m2. Participants were allocated in a 2:1 ratio to 25% CR or ad‐libitum (AL) diets. Serum markers of inflammation (CRP, TNFα, IL‐6, IL‐8, ICAM‐1, MCP‐1), as well as WBC counts (total and subset), and antibody response to hepatitis A, tetanus/diphtheria, and pneumococcal vaccines were measured at baseline and after 1 and 2 y of CR. CR significantly reduced CRP and TNFα relative to AL at 24 mo. The estimated change from baseline to 24 mo was ‐0.65 vs. ‐0.023 μg/mL for CRP (p=0.012 for group effect), and ‐0.77 vs. ‐0.38 pg/mL for TNFα (p=0.025 for group effect). No significant effect was observed for other inflammatory markers. In addition, CR was associated with a small, but significantly lower number of WBC, lymphocytes, and monocytes. There was no significant effect of CR on DTH or response to vaccines. These results suggest that 2 y of CR may reduce key indicators of inflammation, but has only a small or negligible impact on cell mediated immunity.

Grant Funding Source: Supported by NIH U01AG022132, U01AG020478, U01AG020487, and U01AG020480.
Long‐term nicotine exposure elevates the expression of alpha7‐nicotinic receptors (α7‐nAChRs) in human squamous cell lung cancer cells via Sp1/GATA proteins (405.4)
Authors: Dasgupta Piyali , Brown Kathleen , Perry Haley , Lau Jamie , Jones Dennie , Pulliam Joseph , Thornhill Brent , Crabtree Clayton , Chen Y
Published: June 2021

Smoking has a strong association with the development of squamous cell carcinomas of the lung (SCC‐L). Nicotine, the addictive component of cigarettes, promotes the proliferation of SCC‐Ls via the α7‐nicotinic acetylcholine receptors (α7‐nAChRs). We explore the effect of long‐term nicotine treatment on α7‐nAChR levels in SCC‐L in vitro and in vivo. Nicotine increased the expression of α7‐nAChR in a concentration‐dependent and time‐dependent manner in three human SCC‐L cell lines. We also found that the levels of α7‐nAChR in SCC‐Ls (isolated from heavy smokers) were greater than the levels in SCC‐L tumors isolated from moderate smokers. The upregulation of α7‐nAChR upon nicotine treatment was confirmed in chicken chorioallantoic membranes (CAM) models. Real‐time PCR and luciferase assays showed that nicotine increased α7‐nAChR levels by transcriptional mechanisms in SCC‐L cells. ChIP‐Re‐ChIP showed that nicotine induced the binding of GATA4 or GATA6 to Sp1 on the α7‐nAChR‐promoter, thereby increasing its levels in H520 SCC‐L cells. We also performed ChIP‐re‐ChIP assay in SCC‐L tumors isolated from patients with heavy to moderate smoking history and obtained similar results. Long‐term nicotine exposure could upregulate α7‐nAChRs on SCC‐L, thereby promoting its progression and metastasis. Our data is relevant to SCC‐L patients exposed to nicotine via second‐hand smoke or nicotine cessation devices.

Grant Funding Source: Supported by the Flight Attendant Medical Research Institute YCSA Grant and an NIH R15‐AREA Grant
Molecular basis of infantile Batten disease: impact of disordered palmitoylated protein degradation on the nervous system (466.1)
Authors: Hofmann Sandra , Lu Jui‐Yun
Published: June 2021

S‐palmitoylation (or more generally, S‐fatty acylation) is a common cysteine modification of proteins that plays key roles in protein stability, protein‐protein and protein‐membrane interaction. Palmitoylated proteins are abundant in neuronal cells. A final pathway for palmitoylated protein degradation involves an enzyme, palmitoyl‐protein thioesterase (PPT1), a specialized lipase of the lysosome. An inborn error of metabolism, infantile neuronal ceroid lipofuscinosis (also known as infantile Batten Disease), results from PPT1 deficiency and the subsequent inability to degrade palmitoylated proteins. Severely affected children are normal to the age of 12‐18 months, after which they display cognitive and motor regression, seizures, and blindness. Partial deficiencies may result in psychiatric manifestations and dementia. Over 60 mutations have been described. Treatment approaches have included bone marrow transplantation, substrate reduction, and neural stem cell transplantation but these have been unsuccessful thus far. Enzyme replacement therapy, which may be beneficial for visceral manifestations of the disease, is in preclinical development, and ways to deliver enzyme to the central nervous system are being sought. Improved understanding of protein palmitoyltransferases and their substrates in the nervous system is expected lead to treatment for this and related disorders.
β‐Glucan particles as a vaccine platform with intrinsic adjuvanticity (469.3)
Authors: Levitz Stuart
Published: June 2021

Most licensed vaccines work by promoting protective antibody responses. However, some populations, such as the elderly and the immunocompromised, generally have poor antibody responses to conventional vaccines. Moreover, for many infectious and neoplastic diseases, vaccines that arm adaptive T cell responses appear necessary. Thus, a major challenge in vaccinology is the development of platforms and adjuvants that effectively promote protective T cell and antibody responses. The immune system has evolved to innately recognize components of the fungal cell wall, particularly β‐glucans. Our research has focused on how innate recognition of the fungal cell wall can be exploited for vaccine development. To achieve this aim, we have used glucan particles (GPs) as a novel vaccine platform. GPs are hollow, highly purified microcapsules prepared from Saccharomyces cerevisiae cell walls. GPs are composed predominantly of β‐1,3‐glucan and are recognized by β‐glucan receptors (particularly Dectin‐1) on dendritic cells and other phagocytes. GPs also potently activate complement, resulting in opsonization and recognition by complement receptors. GPs can be loaded with antigens and immunomodulators such that the “payload” is released following phagocytosis. We have demonstrated robust and long‐lasting antigen‐specific T cell (Th1‐ and Th17‐biased) and antibody responses following immunization of mice with GPs “encapsulated” with antibody. Moreover, vaccination of mice with GPs loaded with fungal antigens can protect mice against lethal challenges with the pathogenic fungi Cryptococcus neoformans and Histoplasma capsulatum.
Teaching clinical anatomy of the knee using a 3‐column methodology approach (536.6)
Authors: Benninger Brion , Westlake Babe
Published: June 2021

INTRODUCTION. The knee is a weight bearing synovial joint, which is frequently injured. May lead to significant time off work and loss of fitness activity resulting in a sedentary lifestyle. Contemporary methodology of knee anatomy teaching applies a systems approach (SA). SA to the knee does not intuitively integrate the mechanism of injury (MoI), symptoms and examination with common pathologies. Musculoskeletal training during family practice residency is approximately 10% of the curriculum. Objective of this study was to apply a 3‐column approach of teaching knee anatomy. METHODS. Knee was divided into 3 columns and taught as a tutorial to first year medical students during lab versus a systems lecture approach. Likert scale and random interviews were conducted. RESULTS. A 3‐column approach was successfully taught and well received regarding Likert scores and interview analysis. DISCUSSION. SA to knee anatomy teaching often leaves a void between classroom and clinic. Musculoskeletal specialists focus on the posteromedial and posterolateral regions of the knee. This pilot work successfully applied a 3‐column approach integrating structures, MoI, examination and symptoms with common pathologies. CONCLUSSION. This study suggests a 3‐column teaching approach may provide a successful platform enabling students to apply knee anatomy in the clinical arena resulting in critical thinking aiding diagnosis.
Cardioprotective and anti‐atherosclerotic use of a biopolymer‐encapsulated glycosyltransferase inhibitor (607.9)
Authors: Chatterjee Subroto , Bedja Djahida , Mishra Sumita , Amuzie Christine , Foss Catherine , Pomper Martin , Boonipat Thanapoom , Nair Vineet , Bhattacharya Rahul , Yarema Kevin
Published: June 2021

Although atherosclerosis and cardiac hypertrophy are synonymous with a western diet, very little is known about the effects of lowering glycosphingolipid load on interfering with such diet ‐induced phenotypes. Herein, we show that encapsulation of a glycosphingolipid glycosyltransferase inhibitor D‐threo‐1‐phenyl‐2 decanoylamino‐3‐morpholino‐1‐propanol(D‐PDMP) within a biopolymer markedly increased its efficacy in interfering with atherosclerosis and cardiac hypertrophy in Apo E ‐/‐ mice. Our imaging studies revealed that the residence time of 125I ‐tagged biopolymer encapsulated D‐PDMP in mice is ~24hrs compared with 1hr for native D‐PDMP.

ApoE‐/‐ mice fed a western diet had markedly increased coronary artery atherosclerosis, aortic intima thickness (AoIMT ) and vascular stiffness. This was completely reversed by feeding mice 1mpk D‐PDMP encapsulated within the biopolymer (1BP) and this was comparable to mice fed 10mpk D‐PDMP alone. The activity of glycosyltransferases,,lipids and genes implicated in their regulation were markedly increased in apo‐/‐ mice fed western diet and this was interfered by treatment with 1BP.

Intriguingly, western diet also caused extensive cardiac hypertrophy accompanied by a time ‐dependent decrease in fractional shortening and an increase in left ventricular mass. Accompanied with increased gene expression for atrial naturetic factor (ANP) and brain naturetic factor (BNP)‐established biomarkers of cardiac hypertrophy. Treatment with 1BP and or 10mpK D‐PDMP reversed cardiac hypertrophy biomarkers and cardiac function e.g. fractional shortening as well as left ventricular mass. Thus, encapsulation of D‐PDMP within a biopolymer is at least 10‐fold more efficacious in interfering/ameliorating atherosclerosis and cardiac hypertrophy in western diet fed apoE‐/‐ mice as compared to D ‐PDMP alone.

Grant Funding Source: Supported by NHLBI grant P01HL107153.
Pentoxifylline induces GSK‐3β‐independent proteasomal degradation of cyclin D1 and arrests renal cancer cells in the G1 phase (616.5)
Authors: Cai Wesley , Mastrandrea Nick , Tham Kim , Monks Terrence , Lau Serrine
Published: June 2021

Cyclin D1 is required for progression from G1 into S phase of the cell cycle. Over‐expression of cyclin D1 causes an increase in cell cycle progression and proliferation. Canonical cyclin D1 degradation is initiated by phosphorylation of Thr286 by GSK‐3β. QTRRE (rodent) and ACHN (human) renal cell carcinoma (RCC) cell lines exhibit elevated levels of cyclin D1. Pentoxifylline (PTX) is used as an adjunct in chemotherapy to treat cachexia. We report that PTX causes a time‐ and dose‐dependent decrease in cyclin D1 levels and G1 cell cycle arrest in QTRRE and ACHN cells. RT‐PCR analysis showed no significant changes in cyclin D1 mRNA. However, PTX’s ability to decrease cyclin D1 was prevented by the proteasome inhibitor, MG‐132. Inhibition of GSK‐3β with LiCl in the presence of PTX failed to rescue cyclin D1 levels. PTX increased pSer9 on GSK‐3β, indicative of an inhibition of GSK‐3β activity. Following siRNA knockdown of GSK‐3β, PTX retained the ability to decrease cyclin D1 levels. Moreover, PTX treatment in the presence of MG‐132 revealed no increase in pThr286 compared to control. Our data indicate that PTX initiates GSK‐3β‐independent proteasomal degradation of cyclin D1 and arrests the RCC cells in the G1 phase. Because our findings demonstrate a novel anti‐cancer property of PTX, its use as an adjuvant therapy in RCC treatment should be further explored.

Grant Funding Source: Supported by ES006694, AstraZeneca Studentship, T32ES016652
Dairy consumption is associated with a lower risk of stunting in Ethiopian children 6‐24 months of age (620.10)
Authors: Ghosh Shibani , Suri Devika , Griffiths Jeffrey
Published: June 2021

Background: Stunting can negatively impacting physical and mental development. Dairy consumption has been associated with lower risk of being stunted in many populations.

Objective: Examine the association between dairy consumption and prevalence of stunting in Ethiopian children 6‐24 months of age.

Methods: Analysis of 2011 Demographic Health Survey data was conducted to examine feeding practices of infants and young children along with types of foods consumed, number of meals consumed, food groups and their relationship to being stunted or not across the different regions of Ethiopia. Correlations and odds ratios were calculated.

Results: Rates of stunting are variable by region in Ethiopia with Addis Ababa showing the lowest rates (13%) and Tigray the highest (52%). This was followed by Amhara, Affar and Bishangul‐Gumuz regions. Dairy was the most common animal source food but was consumed in low amounts in Tigray, Amhara and Bishangul‐Gumuz (10‐20% of children). Most regions less than 2.5 meals and less than 2 groups were consumed by infants aged 6‐24 months. Regions with higher dairy consumptions are more likely to have lower rates of stunting. Consumption of diary was associated with a lower risk of being stunted (χ2=20.2 and p<0.001, adjusted R2 =0.26). Stunted children were likely to report consuming more meat but the association was not significant.

Conclusions: Dairy consumption in Ethiopian children 6‐24 months of age is associated with stunting. Different regions in Ethiopia vary by rates of stunting and consumption of dairy is lowest in regions of Amhara Tigray and Bishangul‐Gumuz but not Affar, all regions where rates of stunting are high.
Mammary cells synthesize insulin during lactation (622.3)
Authors: Hassiotou Foteini , Lai Ching , Filgueira Luis , Stuebe Alison , Hartmann Peter , Geddes Donna
Published: June 2021

The mammary gland undergoes extensive remodeling during pregnancy and lactation to mature into a milk‐secretory organ. This remodeling is accompanied by a series of alterations in gene expression that are fuelled by hormonal changes facilitating maturation of epithelial cells. Insulin, supplied by the maternal circulation, is thought to play a key role in this process. In this study, we examined whether mammary cells endogenously synthesize insulin during lactation. First, we stained rare specimens of human lactating breast tissue for insulin and found that some, but not all, mammary epithelial cells were positive for insulin. We subsequently confirmed this finding with FACS. We then detected the transcript for insulin in mammary cells accessed via freshly expressed breastmilk. Transcript levels were highly variable among the breastmilk samples tested, and were significantly higher than in mammary cells accessed from the resting breast (P<0.05). Insulin expression in breastmilk cells correlated with expression of various stem cell genes, such as ESRRB, and appeared to be associated with the stage of lactation. We have for the first time confirmed that the insulin in breastmilk is derived from both the pancreatic beta cells and mammary cells of the lactating epithelium. Furthermore, mammary‐derived insulin may provide developmental signals within the mammary gland as well as contribute to breastmilk insulin.
Adherence to small‐quantity lipid based nutrient supplement among young Burkinabe children (624.19)
Authors: Abbeddou Souheila , Hess Sonja , Yakes Jimenez Elizabeth , Somé Jérôme , Guissou Rosemonde , Ouedraogo Zinewendé , Vosti Stephen , Ouedraogo Jean‐Bosco , Brown Kenneth
Published: June 2021

Background and objective: Adherence to recommended supplementation regimens can affect the impact of the product. Our objective was to compare different approaches for estimating adherence to small‐quantity lipid‐based nutrient supplements (SQ‐LNS) in a randomized clinical trial.

Methods: 2453 children 9‐18mo of age were randomly assigned to receive daily 20g SQ‐LNS with varying contents of zinc. During weekly home visits, reported adherence was collected through caregiver interview and disappearance rate was calculated based on returned packages. In a randomly selected subgroup (n=192), consumption of SQ‐LNS was observed during 12h home visits in 11 and 16mo old children. At 15mo, an independent team interviewed caregivers about consumption of SQ‐LNS during the previous day/week (n=349).

Results: Average daily reported adherence was 97% ± 6%. Disappearance rate also indicated high weekly adherence with 98% ± 5%. By contrast, home observation showed that only 58% and 48% of children at 11 and 16mo, respectively received SQ‐LNS during the observation periods (P visit time=0.51). This resulted in 50% difference between reported and observed consumption of SQ‐LNS. During the 15mo independent interview, mothers reported that 94% and 89% of children consumed the full dose of SQ‐LNS during the previous day/week, respectively.

Conclusion: Discrepancy among results suggests possible over‐reporting of adherence to SQ‐LNS, and consumption by children outside the 12h home observation.

Grant Funding Source: Bill & Melinda Gates Foundation
Healthy meals, healthy families: a pilot intervention to improve nutrition knowledge and confidence to prepare healthy meals among low‐income individuals (624.6)
Authors: Fernandes Nicolle , Driver Stacey , Ellery Jane , Friesen Carol
Published: June 2021

Poor dietary behaviors, limited food preparation skills, and low levels of self‐efficacy to prepare healthy meals have been indicated in low‐income and food insecure populations. The purpose of this pilot study was to determine the effectiveness of a community cooking demonstration at increasing participants’ confidence to prepare healthy meals with limited resources. Subjects included a convenience sample of 23 low‐income adults associated with Head Start (n=7) or a soup kitchen (n=16) in Muncie, IN. Participants attended a one hour presentation that included a slow‐cooker demonstration, taste testing, and basic information about MyPlate and food safety. Subjects completed a pre‐ and post‐assessment to measure any changes in confidence to cook and in general food and nutrition knowledge. Subjects received a free copy of the cookbook “Slow Cooking on a Budget” and a chance to win a slow cooker. Results indicated that, although there were no significant improvements in participants’ confidence to prepare healthy meals (39.3±11.3 vs. 44.5±9.1; t=1.76, p=0.25), subjects experienced significant gains in knowledge related to the MyPlate food guide (1.2±0.5 vs. 1.8±0.8; t=2.82, p=0.01) and basic food safety (0.7±0.9 vs. 2.5±1.0: t=6.05, p<0.001). Further research is necessary to identify effective strategies for parlaying increased nutrition knowledge into improved self‐efficacy and behavior change.
Nutri one‐on‐one: improving patients’ metabolic profile with one‐on‐one nutritional coaching in a clinical setting (627.1)
Authors: King Jennifer , Harris Jeffrey , Kuo David , Daghigh Farzaneh
Published: June 2021

Introduction: More than one‐third of U.S. adults (35.7%) are obese. Some of the leading causes of death are due to complications of chronic conditions related to metabolic disorders and obesity. One on one health coaching will assist people in adopting healthy lifestyle behaviors that prevent and control diseases through phases of effective goal setting, motivational interviewing, and collaboration with health care providers.

Objectives: This study’s aim was to positively influence patients’ nutritional habits and lifestyle through a brief one on one coaching session. The effects of one on one nutritional education are analyzed through goal setting, motivational lessons, and follow‐up to improve lifestyle.

Methodology: Patients were interviewed to gain insight into their daily nutritional routines and patients’ anthropometric histories were obtained. Patients were then encouraged to set a primary health goal. A personalized nutritional lesson was administered to address the health goal and current nutritional behaviors. The patient and health coach then arrived at three simple and obtainable lifestyle modifications to reach the initial goal. Obstacles were addressed and a follow‐up phone call was scheduled to obtain self‐reported results and insure accountability and support.

Results: The study included 57 adult patients (39 female, 18 male) with metabolic disorders and demonstrated an overwhelming success with nutritional fact recollection, progress on the readiness scale, goal achievement, and in office experience satisfaction. A majority of patients showed willingness and motivation to continue implementing a healthy lifestyle.

Conclusion: Personalized one on one nutritional coaching tailored to patient’s goal proved to be successful. Tailored education on healthy living, nutrition, and motivational techniques continued to create positive behavior modification. The follow‐up sessions provided reinforcement in sustaining success.

Grant Funding Source: Philadelpollege of Osteopathic Medicine & CCDA
Higher fat mass percent is associated with decreased HIV disease progression in HIV+ adults (628.2)
Authors: Ramamoorthy Venkataraghavan , Riedel Pamela , Baum Marianna , Greer Pedro , Li Yinghui , Dizon Kimberly , Martinez Sabrina , Luisi Sonya , Nagi Gagandeep , Fleetwood Christina , Stewart Tiffanie , Campa Adriana
Published: June 2021

Background: This longitudinal study examines the relationship between FM%, an indicator for higher caloric intake and markers of disease progression (CD4 cell counts and viral loads).

Methods: A secondary analysis was done on data gathered from an observational study on HIV infected patients. FM% was obtained from bio impedance analysis and CD4 cell counts and viral loads were obtained from medical charts. A total of 267 participants were included. Multiple Linear Regressions were used for cross‐sectional analysis and Mixed Models were used for overtime analysis. Statistical significance was set at p<0.05.

Results: Mean age was 49.41±5.61 years, 62.1% were males and 71% were African Americans. The mean baseline CD4 counts were 516.71± 342.39 cells/mm3 and viral loads were 2.5±1.1 log10 copies/μL. FM% was associated with higher CD4 cell counts (β=‐5.39, p=0.019) at baseline and this association strengthened by controlling for age, gender, ART and BMI (β=‐5.72, p=0.013). FM% was also associated with higher CD4 cell counts over six months (β=4.619, p=0.016).

Conclusion: Higher FM % measured cross‐sectionally and over time predicted improved markers of HIV disease progression.

Grant Funding Source: NIDA
Greater obesity among breast cancer cases compared to controls from the Breast Cancer Risk Model in Pacific Islander Study in Guam and Saipan (628.8)
Authors: LeonGuerrero Rachael , Novotny Rachel , Wilkens Lynne , Blas Michelle , Chong Marie
Published: June 2021

The BRISK study compared BMI and waist circumference measurements of breast cancer cases (n=107) versus controls (n=184). In this case‐control study of women (n=291) living on Guam and Saipan, demographic, medical history and anthropometric measurements, including height, weight, and waist circumference were collected from each participant. BMI was classified as obese (BMI蠅30), overweight (BMI 25‐29.9), or healthy weight (BMI<25). A waist‐for‐height ratio greater than 0.5 was used to classify participants as ‘at risk’. Cases and controls did not differ in body weight (μ=74.3kg) or BMI (μ = 30.4). However, waist circumference was higher (p<0.05) among cases versus controls (100.1 cm versus 95.8 cm). A higher proportion of controls were ‘healthy weight’ (BMI<25) compared to cases (29.2% versus 18.5%); cases were more likely to be either ‘overweight’ and/or ‘obese’ compared to controls. A high proportion of both cases and controls were classified ‘at risk’, as indicated by waist‐for‐height measurements (97.5% and 87.1%), and a higher proportion of cases vs controls were considered ‘at risk’. Anthropometric data suggests that both breast cancer cases and controls are at elevated risk for chronic disease, though cases have higher levels than controls.

Grant Funding Source: Supported by a NCI MI/CCP Grant #U54‐CA‐143727