bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated Transcriptomic, Proteomic, and MicroRNA Data Identify Key Regulators of Developmental and Repair Processes During Tail Regeneration in the Green Anole Lizard
Authors: Hutchins Elizabeth , Eckalbar Walter , Pendarvis Ken , McCarthy Fiona , Lake Douglas , Kusumi Kenro
Published: June 2021

Among amniotes, mammals and birds display only limited ability for regeneration in the adult. However, lizards retain the ability to lose their tails and regrow a functional replacement that includes newly formed hyaline cartilage, spinal cord, muscle, vasculature, and skin. These newly regenerated tails, which have an organization distinct from the original tail, are formed through a complex process that involves differential expression of hundreds of genes, including those related to wound healing, musculoskeletal development, hormonal response, embryonic morphogenesis, and Wnt pathway activation. We performed whole transcriptome, microRNA transcriptome, and proteome analysis of regenerating tail tip and base and associated tissues in order to investigate gene expression in regenerating tissue. We identified 350 novel and 196 known microRNA precursor families and over 2,000 proteins. Differentially expressed microRNAs in the regenerating tail include miR‐133a, miR‐133b, and miR‐206, which have been reported to regulate regeneration and stem cell proliferation in model systems, as well as three novel microRNAs. Additionally, we integrated microRNA and mRNA expression patterns with proteomic analysis in order to confirm the presence of predicted targets of down‐regulated microRNAs. Using a combination of whole and microRNA transcriptome with proteome data, we have identified key microRNA regulators and their targets that control the regenerative process in the green anole lizard, which has value for translation to future regenerative therapies.
Impaired Vascular Oxygen Sensing Affects the Maintainance and Regeneration of the Bone Marrow
Authors: Ramirez‐Bergeron Diana , Tao Jiayi , Han Yu , Gomer Alla
Published: June 2021

Hypoxia provides critical cues in specialized niches that sustain stem cells. The bone marrow (BM) stem cell niche is a highly hypoxic microenvironment known to support hematopoietic stem and progenitor cells (HSPCs). These cells reside in anatomical vascular sub‐compartments within the bone marrow whereby the quiescent hematopoietic cells (HSCs) are found near arterioles in the endosteal zone while the more proliferative hematopoietic progenitor cells (HPCs) occupy the perivascular niche zone containing specialized fenestrated sinusoidal endothelial cells (SECs). Using an inducible genetic system, we conditionally inactivated the required HIF­β subunit [Aryl hydrocarbon receptor nuclear translocator (ARNT)] of Hypoxia Inducible Factor (HIF) in the endothelium in the vasculature of 8‐ week old mice (ArntiΔEC) to understand its transcriptional role in directing the maintenance of the BM stem cell niche. We observe that compromised endothelium of ArntiΔEC mice results in a distinct disturbance to the BM's vascular microenvironment. Following 5‐Fluorouracil (5‐FU) treatment, ArntiΔEC mice experience myelodysplasia, impaired BM revascularization and regeneration. There is a reduction in proangiogenic transcript levels in RNA isolated from bone marrow's of 5‐FU myeloablated ArntiΔEC mice. Lethal levels of γ‐irradiation result in hematopoietic failure and death of ArntiΔEC mice as transplanted control BM cells fail to engraft and reconstitute their bone marrow. These results support our hypothesis that endothelial‐HIF is required for orchestrating the maintenance and regeneration of the vasculature in the bone marrow's stem cell niche in response to stress.
FGF and TGFβ Signaling are Required During Secondary Chondrogenesis in the Jaw Skeleton
Authors: Woronowicz Katherine , Jaul Danielle , Herfat Safa , Fields Aaron , Lotz Jeffrey , Schneider Richard
Published: June 2021

Induction and maintenance of secondary cartilage requires mechanical stimulation and signal transduction. Secondary cartilage forms on the surface of bone within select articulations and muscle insertions, and represents an adaptive response to mechanical force. As in the human jaw, the coronoid process of the duck forms through secondary chondrogenesis at the mandibular adductor muscle insertion. In quail, the coronoid process develops without secondary cartilage. To identify mechanical mechanisms underlying secondary chondrogenesis, we compared embryonic motility in quail and duck, and find that the onset and frequency of activity is equivalent. We then investigated if the species‐specific anatomy of duck promotes secondary chondrogenesis via differences in the mechanical environment. 3D reconstructions show how the mandibular adductor inserts laterally in duck and dorsally in quail, and finite element analysis suggests that the duck coronoid process experiences tension and shear whereas quail experiences primarily tension. Shear force is known to promote chondrogenesis. To identify molecular mechanisms that may mediate the response to mechanical force, we blocked FGF and TGFβ signaling with small molecule inhibitors. Secondary cartilage failed to form in treated embryos. Our results suggest that shear force stimulates FGF and TGFβ signaling to induce and/or maintain secondary cartilage.
The Temporal and Spatial Development of Vascularity in a Healing Displaced Fracture
Authors: Mignemi Nicholas , Yuasa Masato , Barnett Joey , Cates Justin , Nyman Jeffry , Obremskey William , Okawa Atsushi , Schwartz Herbert , Stutz Christopher , Schoenecker Jonathan
Published: June 2021

Introduction

Underlying vascular disease is an important pathophysiology shared among many co‐morbid conditions associated with poor fracture healing, such as diabetes, obesity, and age. Determining the temporal and spatial patterns of revascularization following fracture is essential for devising therapeutic strategies to augment this critical reparative process. These studies were designed specifically to i) validate the classic model of fracture revascularization, ii) assess the association between intramedullary and periosteal angiogenesis and iii) elucidate the expression of VEGF/VEGF‐R in relation to the classic model.

Methods

Mid‐shaft femoral osteotomies (n=52) were followed with X‐ray, μCT, angiography and histology for 7‐42 days.

Results

Representative data of vascularity during fracture repair is presented in figure 1. Fractures with disruption of the medullary vasculature revascularize initially through the development of vascular anastomoses between the medullary vasculature and the areas of periosteal vascular engorgement resulting from interruption of medullary vascularity at the fracture site (Figure 2). Following the intramembranous phase or repair, fracture healing proceeds through endochondral mediated angiogenesis and bone formation under the control of VEGF and it's receptors.

image

Conclusion

From these data, in conjunction with classic studies of fracture angiogenesis, we propose a novel model defining the process of bone revascularization.
Development of a Serum‐free, Three Dimensional Cell Culture Model for Primary Human Articular Chondrocytes to Test Potential Therapeutics
Authors: Bundens Grace , Miller Lawrence , Lackman Richard , Cho Ellen , Chmielewski Sarah , Milton LaBraya , Selim Abdulhafez , George‐Weinstein Mindy , D'Angelo Marina
Published: June 2021

The objective of this study was to establish a culture system of primary human articular chondrocytes with which to test novel drugs for the treatment of osteoarthritis (OA). Articular cartilage was obtained from OA subjects undergoing total knee arthroplasty (TKA) or above knee amputation (AKA) for pathology unrelated to OA. Chondrocytes were isolated by protease digestion and cultured in alginate at 2, 5, 10 x 106 cells in serum‐free medium. Production of collagen degradation products was measured in days 2 and 5 culture medium and day 5 cell‐associated matrix. The optimal plating density was 5x106 cells/culture, as determined by Lowry protein analysis. Type I collagen telopeptide breakdown products were higher in cultures established from the femoral condyles than from the patella, and in OA cultures compared to AKA controls. Type II collagen telopeptides were also detected in both OA and TKA cultures; however, the amounts of these telopeptides were not significantly different in the two types of cultures. These results demonstrate that human articular chondrocytes survive and are metabolically active when cultured in this serum‐free, 3D culture system. The femoral condyles and tibial plateau were the optimal sites for tissue harvesting. With this model system we can effectively measure clinical endpoints for testing new drugs that may reduce tissue destruction in OA.

This work was funded by PCOM, CMSRU, Cooper Foundation and Cooper Bone and Joint Institute.
The Anatomy Schema Network
Authors: Nyamse Victor , Parker Caroline
Published: June 2021

The Anatomical Schema network (ASN) is proposed as a framework that defines how anatomical information is stored in memory of an anatomy learner and serves as an indicator of the learner's competency. Information stored in Long Term Memory plays a vital role in all aspect of education and schema theory is seen as one of the most effective ways of conceptualizing information storage. It proposes that information is stored in memory as mental structures called schemata that consists of individual units and the interlinks between them. Based on this understanding, the anatomical schema (AS) is proposed as a hypothetical mental structure that stores anatomical information in units relating to an anatomical structure or region and the interlinks between those units.

ASN groups these AS into three levels based on the nature of information in the individual units and the complexity of the interlinks between the units. AS in the first level have information units on a single anatomical structure and have a maximum of three interlinks. The second level contains AS with information units related to more than one anatomical structure and less than six interlinks. Units of AS in the third and final level have an infinite number of interlinks and contain information relevant to a particular professional context. The framework has been applied to anatomical taxonomies for learning activities (ALA), textual representation AI. A similar philosophy is applied in IAPP for assessments.
Vaginal Microbiota, Racial/Ethnic Groups, and Risk of Preterm Birth
Authors: Foxman Betsy
Published: June 2021

Premature birth (PTB) is a major cause of infant mortality. Infection, both overt and subclinical, accounts for ~25‐40% of all PTBs. When the composition of vaginal microbiota is perturbed, as occurs during bacterial vaginosis (BV), there is an increased risk of PTB. However, the effects of BV treatment on reducing PTB rates have been disappointing, even resulting in an increased risk of PTB in some groups. BV prevalence varies by racial/ethnic group being highest among Black Americans ‐ as is risk of PTB. I discuss the variations in and interactions among taxa in the vaginal microbiota by racial/ethnic group, and review the growing literature suggesting that some of the increased risk of preterm birth among Black Americans is attributable to differences in immune response to specific vaginal bacteria, rather than differences in carriage rates. Further, I present evidence that the associations of specific microbes with PTB are contingent of the presence of co‐factors, not only host behaviors, but the other members of the microbial community and the overall host response to that community.
Topoisomerase‐Induced DNA Cleavage at Ribonucleotide Misincorporation Sites
Authors: Pommier Yves , Huang Shar‐Yin , Williams Jessica , Kunkel Thomas
Published: June 2021

An estimated two ribonucleotides (rNMPs) per kilobase are mis‐incorporated into DNA due to high ratios of rNTP/dNTP pools in vivo, placing rNMPs as the most frequent source of DNA damage to date (Williams and Kunkel, 2014). The main pathway for rNMPs removal is the RNaseH2‐dependent pathway. When RNaseH2 is deleted in yeast, a specific topoisomerase I (Top1)‐dependent mutator effect develops: accumulation of short deletions within tandem repeats at genomic ribonucleotide sites generated by Top1 (Kim et al., 2011). We will discuss how ribonucleotide misincorporations induce replication stress and hyper‐recombination phenotype, which are alleviated upon deletion of the Top1 gene. On the other hand, ribonucleotide misincorporation is aggravated by inactivation of homologous repair (HR) in yeast strains. These in vivo data suggest that HR is important in the repair of Top1‐induced DNA damage in the presence of high levels of rNMPs. Using oligonucleotides with rNMPs incorporated at different positions, we show that Top1 can generate frequent DNA nicks with 3′ blocking ends (2′,3′‐cyclophosphates). In addition, we will demonstrate how a single rNMP is sufficient to generate recombination products and double‐strand breaks, a potential source of replication stress in vivo. Finally, we will show that faulty religation by Top1 generated 2‐nucleotide deletion, and the deletion products no longer contained rNMPs. Together these findings demonstrate the potential danger of Top1 activity at ribonucleotide misincorporation sites

· Kim, N., Huang, S. Y., Williams, J. S., Li, Y. C., Clark, A. B., Cho, J. E., Kunkel, T. A., Pommier, Y., and Jinks‐Robertson, S. (2011). Mutagenic processing of ribonucleotides in DNA by yeast topoisomerase I. Science 332, 1561‐1564

· Williams, J. S., and Kunkel, T. A. (2014). Ribonucleotides in DNA: origins, repair and consequences. DNA Repair (Amst) 19, 27‐37.
Glycemic and insulinemic responses are blunted by the consumption of a smoothie‐type beverage containing a whole‐grain fiber composite ingredient
Authors: O'Connor Lauren , Campbell Wayne
Published: June 2021

This study assessed the effects of consuming a novel co‐processed composite ingredient comprised of a viscous fiber and whole‐grain high‐amylose maize flour, a rich source of resistant starch, on glycemic and insulinemic responses to meals. It was hypothesized that a smoothie‐type beverage containing the ingredient would blunt the post‐prandial responses in serum glucose and insulin concentrations compared to a beverage containing maltodextrin (MD). Nineteen healthy men and women (26 ± 3 years, BMI 24.3 ± 2.8 kg/m2) participated in 2 testing days (randomized crossover design) separated by at least 1 week. Subjects were counseled to consume a standard low‐fiber diet on each day prior to testing. On each testing day, blood samples were collected at baseline and incrementally for 8 hours after consuming a standardized low‐fiber meal with a beverage containing the composite ingredient or MD; a standard low‐fiber meal (without the composite ingredient or MD) was consumed 4 hours after the first meal. The composite ingredient blunted the post‐prandial glycemic (AUC0‐8h 3548 ± 1722 vs. 5352 ± 3564 mg/dL•480 min) and insulinemic (AUC0‐8h 7612 ± 3799 vs. 9769 ± 5156 µU/mL•480 min) responses (p<0.05) versus MD. Glycemic and insulinemic responses were lowered by 53 and 78%, respectively, after the first meal and by 17 and 11% after the second meal (p<0.05) with consumption of the composite ingredient. These findings support the use of this composite ingredient for insulin‐mediated glucose control.

Support

Ingredion Incorporated; NIH UL1TR001108; Purdue University
Comparing Growth Assessments Using CDC and WHO Reference Data in Native Hawaiian Pacific Islander Children: Baseline Data from the Children's Healthy Living (CHL) Program in Hawaiʻi
Authors: Esquivel Monica , Li Fenfang , Novotny Rachel
Published: June 2021

In the diverse US Affiliated Pacific Centers for Disease Control (CDC) 2000 and 2006 World Health Organization (WHO) reference data are available to assess child growth. WHO reference data includes children who met recommended breastfeeding guidelines from six countries, while CDC data describes growth of US children where few were breastfed. Baseline data from the CHL program in Hawai'i (n=941) was used to calculate BMI z‐scores and percentiles to compare growth relative to the two reference data sets and identify the role of breastfeeding history, age, sex, and ethnicity on growth assessment. Mean BMI z‐scores calculated with CDC reference data were lower than WHO (z‐score difference=‐0.31, p<0.001). A general linear model on BMI z differences against child age, sex, ethnicity and breastfeeding history showed the difference by CDC reference was greater in boys than girls (z score difference = 0.20, p<0.001). No difference was found by breastfeeding history, age or ethnicity. Kappa statistics showed strong agreement between the two references on CDC defined BMI categories (weighted Kappa=0.50, p<0.001), with percentage of agreement highest for healthy weight (92%), followed by obese (85%), then overweight (76%). CDC and WHO growth reference data samples differ by breastfeeding history and ethnicity; differences between BMI z‐scores calculated from the two reference data sets were not related to either factor. Researchers and practitioners can choose either reference data to analyze BMI and child growth in NHPI children but should be cautious that CDC growth references may underestimate childhood overweight and obesity, and delay early intervention.
A Nutrient Profiling System for the (Re)Formulation of a Global Food & Beverage Portfolio
Authors: Vlassopoulos Antonios , Masset Gabriel , Leroy Fabienne , Drewnowski Adam
Published: June 2021

BACKGROUND

One goal of nutrient profiling models is to help the food industry reformulate its products for better public health. The Nestle Nutrition Profiling System (NNPS) was developed to help screen a global product portfolio for improved nutrient density.

METHOD

For nutrient profiling purposes,products in the portfolio were assigned to 3 main food groups and 32 food categories, based on consumer research data, patterns of food use, and insights from food technology. The groups were larger and smaller meal components (n=6 & n=18, respectively), and accessories (n=6). Nutrient targets were linked to age‐adjusted dietary guidelines. Nutrient density was assessed per serving. The NNPS algorithm ensured that excessive amounts of disqualifying nutrients could not be compensated for. An external expert board provided feedback during NNPS development.

RESULTS

Nutrient targets for larger meal components were based on energy and nutrients per serving (% of energy or %DV), whereas those for snacks and accessories were based only on %DV of nutrients per serving. Maximum energy targets per serving were set to drive optimal serving sizes. The NNPS outcome was set as pass/fail, largely based on the presence of excess disqualifying nutrients. The relative distance of portfolio products from desired target goals then became the basis for product reformulation. Analysis of 14 randomly selected products showed that reformulation using NNPS resulted in a reduction of the content in all disqualifying nutrients.

Nestlé After vs Before

Added Sugars
SFA
Sodium
Total Fat

Chicken soup (250mL)
‐100%
‐100%
‐6%
‐47%

Chocolate milk (200mL)
‐14%
‐4%
0%
‐3%

Vegetable Lasagna (225g)
0%
‐42%
‐15%
‐25%

Vanilla Ice Cream Sandwich (70g)
‐50%
‐75%
‐39%
‐79%

Chocolate cereal bar (20g)
‐66%
‐97%
‐58%
‐92%

Apple drink (240mL)
‐54%
0%
‐75%
0%

Bacon slices (20g)
‐60%
‐42%
‐73%
‐44%

Water ice (85g)
‐35%
‐
0%
‐

Pepperoni pizza (143g)
25%
‐14%
‐13%
‐30%

Mousse type dessert (75g)
1%
‐63%
‐63%
‐68%

Puff pastry (28g)
‐42%
‐11%
10%
‐6%

Mayonnaise (15g)
‐80%
‐1%
1%
0%

Fruit Jellies (22g)
‐10%
‐
‐61%
‐

CONCLUSION

The NNPS can help ensure that each product delivered to the consumer is (re)formulated to address public health needs and assist in the adoption of a balanced diet.
Serum Metabolomic Response to Vitamin E Supplementation in a Controlled Cancer Prevention Trial
Authors: Albanes Demetrius , Moore Steven , Weinstein Stephanie , Mondul Alison
Published: June 2021

The Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention (ATBC) Study found that vitamin E supplementation led to 32% lower prostate cancer incidence, but two subsequent trials were not confirmatory. To increase our understanding of the effects of α‐tocopherol supplementation on cancer risk by searching for novel biochemical signatures, we examined the on‐study change in serum metabolomic profiles of men randomized to receive the ATBC α‐tocopherol supplement. Fifty men were randomly selected from each of the four trial groups: α‐tocopherol (as all‐rac‐α‐tocopheryl acetate), ß‐carotene, both supplements, and placebo. Metabolomic profiling of baseline and follow‐up fasting serum was conducted at Metabolon, Inc. (Durham, NC) using ultrahigh‐performance liquid chromatography/mass spectroscopy and gas chromatography/mass spectroscopy. Of the 500 metabolites we identified, 24 changed in response to supplementation with α‐tocopherol at p<0.05. After correction for multiple comparisons with a threshold of p<0.00021, the top five metabolite signals were for α‐CEHC sulfate (β=1.512, p=1.5x10‐38), α‐CEHC glucuronide (β=1.412, p=1.0x10‐31), α‐tocopherol (β=0.974, p=2.2x10‐13), γ‐tocopherol (β=‐0.902, p=1.8x10‐11), and β‐tocopherol (β=‐0.731, p=9.4x10‐8). Interestingly, three amino acids were also altered by the α‐tocopherol supplementation, but below the Bonferroni level of statistical significance: beta‐alanine, ornithine, and N6‐acetyllysine (β=‐0.4, p=10‐2‐10–3). Comparison of the metabolomic profile found here to those in other vitamin E prevention trials may shed light on their apparently discordant findings.

Research support: Intramural Research Program of the National Cancer Institute, NIH.
Household Poverty Does Not Correlate With Micronutrient Malnutrition: Preliminary Findings From A Cross‐sectional Survey in Madhya Pradesh
Authors: Perumal Nandita , Kaur Supreet , Sachdeva Ruchika , Sankar Rajan , Jungjohann Svenja
Published: June 2021

Household poverty may be a useful indicator to identify micronutrient deficient populations. We aimed to determine the correlation between household poverty and prevalence of micronutrient deficiencies among children 6‐59 months of age and their mothers. A multistage stratified cross‐sectional survey conducted in Madhya Pradesh, India, was used. Household risk of poverty was assessed using the multidimensional poverty index (MPI), which measures deprivations in health and nutrition, education, and living standards. Hemoglobin <11‐12 g/dl, inflammation corrected serum retinol <0.70 umol/L, and 25‐hydroxyvitamin D concentration <20 ng/ml, were used to classify anaemia, vitamin A deficiency, and vitamin D deficiency, respectively. Chi‐square test and Spearman's correlation were used to evaluate associations. Micronutrient status of women and children were assessed in 583 households. Of these, 74 (13%) households were MPI‐poor. 471 (81%) children and 521 (89%) mothers were deficient in at least one micronutrient. Among MPI‐poor households, 78% (58/74) of children and 92% (68/74) of women were micronutrient deficient. MPI was not correlated with micronutrient deficiency among children (p=0.57) or mothers (p=0.62). In this study, children aged 6‐59 months and their mothers had a high burden of micronutrient deficiencies, regardless of household poverty. Further research is needed to adapt poverty indices to better identify populations vulnerable to micronutrient deficiencies.
An integrated agriculture‐nutrition‐health program increased maternal knowledge on health and nutrition in Western Kenya
Authors: Webb Girard Amy , Wanjala Rose , Okuku Haile , Levin Carol , Cole Donald , Low Jan
Published: June 2021

The Mama SASHA project integrated an orange flesh sweet potato (OFSP)‐focused, agricultural‐nutrition education intervention into delivery of routine health services and pregnant women's clubs. The aim was to improve the diets, nutrition and health of pregnant / lactating women and children. We enrolled 505 women from intervention and control facilities at their first ANC visit in early pregnancy and followed them to 9 months postpartum. The proportion of intervention women who had heard of VA increased significantly from 43% to 75% (p<0.05); no change was observed among controls (24.3% at enrollment and 25.9% at 9 mos). Only 2.6% of enrolled mothers could identify any functions of VA at enrollment; 5% could name 3 VA rich foods. By 9 months postpartum, 10.9% of intervention mothers vs. 4.2% of control mothers, could identify 2 functions of VA (p<0.05); 15% of intervention and 12% of control mothers could identify 3 VA rich foods. Awareness of early initiation, exclusive breastfeeding to 6 months, continued breastfeeding to 2 years and optimal complementary feeding practices increased in both groups; however the increase in the proportion indicating that mothers should initiate breastfeeding within 1 hour of birth was greater among intervention mothers. There were no differences in knowledge of other infant feeding practices. An integrated agriculture‐nutrition‐health linkages project increased VA knowledge but had limited benefit beyond standard counseling on awareness of other optimal infant and young child feeding practices.
Caffeine, coffee and tea in relation to risk of hip fracture in The Singapore Chinese Health Study
Authors: Dai Zhaoli , Yuan Jian‐Min , Koh Woon‐Puay
Published: June 2021

The dosage of caffeine or coffee in relation to risk of osteoporotic fractures is unclear. In this study, we examined the associations between intake of caffeine, coffee or tea and risk of hip fracture in the Singapore Chinese Health Study, a prospective cohort of 63,257 men and women (45‐74 years) recruited in 1993 ‐ 1998. At baseline, habitual diet including coffee and tea was assessed by a validated food frequency questionnaire. Multivariate Cox proportional regression model was used to estimate hazard ratio (HR) and its 95% confidence interval (CI). During a mean follow‐up of 9.9 years, we identified 1,630 hip fracture incident cases. Compared with drinking coffee <1cup/d, drinking 蠅3 cups/d increased risk for overall (HR: 1.31, 95% CI: 1.04, 1.64) as well as for men and women separately, whereas drinking 2 cups/d reduced risk in women (HR: 0.86, 95% CI: 0.74, 1.02) but not in men (HR: 1.14, 95% CI: 0.89, 1.45). For daily caffeine intake, women with 200‐<300mg had 14% risk reduction compared to those with<100mg (p<0.05), but not in men. In combined analysis, compared to caffeine <200mg/d, for those with 蠅200mg/d, the risk was reduced in women who drank coffee <3cups/d (HR: 0.85, 95% CI: 0.74, 0.99), but was increased in women who had coffee 蠅3cups/d (HR: 1.32; 95% CI: 1.00, 1.73). Drinking tea was not related to risk of hip fracture. We concluded that daily caffeine 200‐<300 mg or drinking 2 cups/d of coffee may reduce hip fractures in women. However, taking coffee 蠅3 cups/d posed risk in both genders, indicating possible detrimental effects of other compounds from coffee on bone health.
Beliefs Regarding Weight Gain during Pregnancy among Participants of the Special Supplemental Nutrition Program for Women, Infants and Children (WIC)
Authors: Koleilat Maria , Vargas Nancy , Pelina Aaron , Bell Sean , Whaley Shannon
Published: June 2021

Very few qualitative analyses exist on low‐income women's beliefs regarding the consequences of pregnancy weight gain. The objective of this study was to examine the beliefs of pregnant WIC participants regarding the consequences of excessive and too little weight gain during pregnancy. This is a secondary data analysis of data collected for a prospective intervention study to reduce excessive gestational weight gain among WIC participants. Participants were asked to provide their opinion on the effects of gaining too much or too little weight during pregnancy. Overall, women in this analytical sample (N=515) were aged 28.5±6.1 years. The sample was largely Hispanic (66%) and 63.1% of the women were either overweight or obese. When asked about the effects of excessive gestational weight gain, only 15.3% mentioned neonatal complications while 57.9% mentioned maternal complications. In contrast, when asked about the consequences of too little weight gain, 48.4% of women mentioned neonatal complications while 12.8% mentioned maternal complications. Overall, participants lacked knowledge on neonatal complications of excessive gestational weight gain. Our findings support the need for educational interventions to improve knowledge about the effects of excessive and too little weight gain among pregnant WIC participants. Such interventions may be beneficial to achieving appropriate weight gain during pregnancy. This research is supported by UCLA Subaward No. 1920 G QA126.
Omega‐3 Fatty Acids Modify Treatment Effect of High‐Dose B Vitamins in Cognitively Impaired Elderly
Authors: Jernerén Fredrik , Elshorbagy Amany , Oulhaj Abderrahim , Smith Stephen , Refsum Helga , Smith David
Published: June 2021

Objective

To investigate whether plasma omega‐3 fatty acid (FA) concentrations (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) modify the treatment effect of homocysteine‐lowering B vitamins on brain atrophy rates and cognitive decline in a placebo‐controlled trial.

Design

The effect of high‐dose B vitamins in the previously reported VITACOG trial [PLoS ONE 5(9) 2010: e12244] was analysed according to baseline omega‐3 FA concentrations. This study included 168 elderly (蠅70 y) with Mild Cognitive Impairment randomly assigned either to placebo, or to B vitamins.

Results

There was a significant interaction (P = 0.024) between B vitamin treatment and plasma combined omega‐3 FA (EPA+DHA) on brain atrophy rates. In subjects with high baseline omega‐3 FA (˃590 μmol/L), B‐vitamin treatment slowed the mean atrophy rate by 40% compared with placebo (P = 0.023). B‐vitamin treatment had no significant effect on rate of atrophy among subjects with low baseline omega‐3 FA (<390 μmol/L). High baseline omega‐3 FA were associated with a slower rate of brain atrophy in the B‐vitamin group, but not in the placebo group. A similar interaction was found between omega‐3 FA and the beneficial cognitive effects of B vitamin treatment.

Conclusion

The beneficial effect of B vitamin treatment on brain atrophy and cognitive decline was observed only in subjects with high plasma omega‐3 FA. It is also suggested that the beneficial effect of omega‐3 FA may be confined to subjects with good B vitamin status.
Omega‐3 Polyunsaturated Fatty Acids have Sex‐specific Effects on the Phospholipid Fatty Acid Composition and Neurotrophin Expression in the Brain of C57BL/6 Mice
Authors: Feltham Brad , Balogun Kayode , Cheema Sukhinder
Published: June 2021

Increasing the consumption of docosahexaenoic acid (DHA) causes a greater accretion of DHA in the cortex, which is associated with improved cognition. We have shown that omega (n)‐3 polyunsaturated fatty acids (PUFA) alter the expression of neurotrophins, such as brain‐derived neurotrophic factor and nerve growth factor, which regulates proper cortical function. Different regions of the brain carry out different functions; however, it is not known whether a diet high in n‐3 PUFA causes accretion of DHA in different brain regions, with sex and age‐specificity. We fed female C57BL/6 mice semi‐purified diets (20% fat w/w) either high (10% w/w) or low (2% w/w) in n‐3 PUFA before pregnancy, during gestation, and lactation. Male and female offspring were studied at weaning, or continued on their mother's diet for an additional 16 weeks. Brain cortex, cerebellum and brainstem were collected for phospholipid fatty acid analysis and gene expression. Regardless of diet, females at weaning had lower DHA in the brainstem and cerebellum compared to the males at weaning (P<0.0001). In addition, females at weaning had lower DHA in only the cerebellum compared to females at 16 weeks (p<0.0001). DHA was not different in both sexes at 16 weeks in the cerebellum and brainstem; however the levels decreased significantly with age in the male brainstem (P<0.0001). High n‐3 PUFA diet caused accretion of cortical DHA in both sexes at 16 weeks (P < 0.05). It is being investigated whether alterations in the fatty acid composition have an effect on the gene expression of neurotrophins in various regions of the brain. We are the first to show sex and age‐specific accretion of n‐3 PUFA in various brain regions. Supported by NSERC.
Effect of Whole Wheat on the Development of Metabolic Syndrome in Rats Fed Snack Foods
Authors: Chen C‐Y , Smith Donald , Lucio Lorena , Braz Mariana , Blumberg Jeffrey
Published: June 2021

Constituents of whole wheat, such as fiber, phytosterols, and phenolic acids, may act to reduce the development of Metabolic Syndrome (MetS). This study examined whether the addition of whole wheat rusk would ameliorate risk factors of MetS in male Wistar rats induced by human snack foods (SF). Seventeen highly palatable, energy dense SF were mixed in equal proportions and then used in the preparation of the rat diets to mimic a “Cafeteria diet” which appears to play a significant role in the MetS development. Fifty rats were weight‐matched and assigned to one of 5 dietary groups: AIN‐93G (C),) 18% refined wheat rusk (RF), 18% whole wheat rusk (WW), RF+65% SF (SRW) or WW+SF (SWW), provided ad libitum for 24 wk. All diets contained 20% protein and adequate minerals and vitamins. The 5 diets did not affect feed intake, growth rate, organ weight or adiposity. After 24 wk, fasting glucose of the SRW was 14 and 16% larger than C and RW, respectively (P 蠄0.05). In a glucose tolerance test, 30‐min incremental blood glucose of SRW rats was 67 and 60% larger than RW and WW, respectively (P 蠄0.05). Plasma malondialdehyde of SWW rats was 26% lower than SRW (P 蠄0.05). Total Antioxidant Performance in the liver of SRW rats was 10% lower than RW (P 蠄0.05). The diets did not affect biomarkers of inflammation. Thus, SF impaired glucoregulation and hepatic antioxidant defenses, and the addition of whole wheat rusk diminished SF‐induced lipid peroxidation.
Carnosic Acid as the Major Bioactive Component in Rosemary Extract Ameliorates High‐fat Diet‐induced Obesity and Metabolic Syndrome in Mice
Authors: Zhao Yantao , Sedighi Rashin , Wang Pei , Chen Huadong , Zhu Yingdong , Sang Shengmin
Published: June 2021

Rosemary has been used as a natural alternative to synthetic antioxidants in Europe and the United States. In this study, we investigated the preventive effects of carnosic acid (CA) enriched rosemary extract on high‐fat diet‐induced obesity and metabolic syndrome in mice. The mice were given a low‐fat (LF) diet, a high‐fat (HF) diet or a high‐fat diet supplemented with 0.14% (w/w, RE#1L), or 0.28% (w/w, RE#1H) rosemary extract with 80% CA, 0.5% (w/w, RE#2) rosemary extract with 45% CA for a period of 16 weeks. RE#1H and RE#2 diets have the same level of CA. The dietary RE supplementation significantly and dose‐dependently reduced body weight gain, percent of fat, plasma ALT, AST, cholesterol, glucose, and insulin levels and liver weight, liver triglyceride and free fatty acid levels. RE administration also decreased the plasma and liver malondialdehyde, advanced glycation end products (AGEs) levels and the liver expression of receptor for AGEs (RAGE). Histological analyses of liver samples showed decreased lipid accumulation in hepatocytes in mice administrated with RE compared with HF diet fed mice. Meanwhile, RE administration enhanced fecal lipid excretion and increased the liver GSH/GSSG ratio. In conclusion, the present study demonstrated that long‐term dietary CA‐enriched rosemary administration could effectively and dose‐dependently attenuate the development of obesity, metabolic syndrome, and fatty liver in HF diet‐induced obese mice. These beneficial effects may be mediated by decreased lipid absorption, improved lipid, glucose and insulin metabolism, decreased inflammation and oxidative stress.
Elevations in Serum Anti‐flagellin and Anti‐lipopolysaccharide Immunoglobulins are Related to Underweight in Young Tanzanian Children
Authors: McDonald Christine , Tran Hao , Gosselin Kerri , Manji Karim , Gewirtz Andrew , Kisenge Rodrick , Aboud Said , Fawzi Wafaie , Duggan Christopher
Published: June 2021

Background

Antibodies to lipopolysaccharide (LPS) and flagellin have been described as indirect measures of increased gastrointestinal permeability and may be markers of environmental enteric dysfunction (EED), a condition linked to poor child growth.

Objective

To assess whether serum LPS‐ and flagellin‐specific immunoglobulin concentrations are associated with poor growth among young Tanzanian children at risk of EED.

Methods

Blood samples were obtained from 590 children at age 6 wks, 6 and 12 mths. Serum LPS‐ and flagellin‐specific immunoglobulin levels (IgA and IgG) were measured by ELISA. Growth was measured monthly for 18 mths.

Results

At 6 wks, compared to infants with LPS‐IgA, LPS‐IgG, flagellin‐IgA, and flagellin‐IgG levels in the lowest quartile, those with values in the highest quartile were, respectively, 1.93 (95% CI 1.06, 3.51), 2.89 (1.49, 5.61), 2.09 (1.11, 3.91), and 2.67 (1.38, 5.16) times more likely to become underweight (WAZ <‐2) after adjusting for covariates (p <0.05). These 6 wk markers were not related to the risk of stunting (LAZ <‐2). There was no association between any of the markers at 6 or 12 mths and subsequent underweight or stunting.

Conclusion

EED in early infancy, as measured by serum levels of LPS‐ and flagellin‐specific immunoglobulins, is associated with underweight. The relationship between these markers and other EED diagnostic tests requires further study.
Sensitivity and Specificity of Serum Retinol in Determining Vitamin A Deficiency
Authors: Suri Devika , Tanumihardjo Jake , Gannon Bryan , Tanumihardjo Sherry
Published: June 2021

Vitamin A deficiency (VAD) afflicts 190 million children worldwide, increasing the risk of morbidity, mortality and blindness. Serum retinol concentration (SR), a common indicator of VA, is not always associated with liver VA reserves due to homeostatic control and during infection. Sensitivity and specificity are used to evaluate the utility of clinical tests to determine presence of disease. Our objective was to determine the sensitivity and specificity of SR as an indicator of VAD in two rural populations of children from Zambia and Thailand.

VA deficiency was based on cutoffs of <0.1 umol/g for liver VA stores (LVA) calculated using stable isotope dilution and <0.7 umol/L for SR. No Zambian children were found deficient using LVA, but 17% were deficient using SR; no children were deficient using SR in the Thai children, but 68% had VAD using LVA. Because there were no true positive cases of VAD in the Zambia children, sensitivity could not be calculated. Specificity was 83%, meaning that 83% of true negative VAD cases were identified, but 27% were false positives. Conversely in the Thai children there were no VAD cases identified by SR, so there were no true or false positives and thus sensitivity was 0%. Specificity was 100%, meaning that all cases identified as not VAD were true negatives. If there was presence of infection as indicated by elevated CRP, AGP or malaria, specificity was reduced; that is, SR was less likely to identify false positives in children without infection in Zambia.

We found that specificity of SR as an indicator of VAD was between 83‐100%, but sensitivity could not be calculated because in these populations there were no children with VAD as identified by both SR and LVA. Presence of infection reduced the specificity of SR for determining VA status.
Feeding Practices Associated with Toddler Dietary Intake
Authors: Edelson Lisa , Mokdad Cassandra , Martin Nathalie
Published: June 2021

Objective

To explore the relationship between parents' observed feeding practices during a typical day of meals and the toddler's usual intake of food groups.

Methods

Sixty families of 12‐36 mo.‐old children recorded all of children's meals for one full day, plus an additional meal at which they introduced a new fruit or vegetable. These videos were coded for parent and child behavior during mealtimes. Three months later, each family completed three 24‐hr dietary recall interviews, from which intakes of food groups were extracted.

Results

Encouragements: Parents' encouragements of vegetable intake during main meals and the novel vegetable were both positively correlated with typical vegetable intake. There was a trend for encouragements of fruit during main meals to be correlated with children's fruit intake, but no association with encouragements of a new fruit. Significant subtypes of encouragements for fruits at main meals were reasoning, modeling, and pressure; for vegetables, reasoning, modeling, and neutral encouragements.

Other behaviors: Parents who served vegetables at least once during main meals had children with significantly higher typical intakes of fruit, and a trend for eating more whole grains and vegetables. Children of parents who used restriction ate significantly more refined grain and had a trend for eating less fish. Correlations between additional parent behaviors and intake will also be presented.

Environment: Compared to those who did not watch TV during meals, children who had a TV/screen on during at least one meal ate less fruit, fish, and alternative proteins, with a trend for eating less whole grain and more dairy.

Conclusions

Mealtime practices such as how new foods are introduced and TV viewing during meals are associated with children's intake of many food groups.
Obesity‐induced Inflammation in Human Mammary Tissues: a Microenvironment Favorable for the Development of Postmenopausal Breast Cancer
Authors: Roubert Agathe , Lyu Lin , Pfalzer Anna , Gauger Kelly , Choi Woojung , Schneider Sallie , Liu Zhenhua
Published: June 2021

Epidemiological studies have convincingly suggested that overweight and obesity are a critical risk factor for postmenopausal breast cancer with a 12% increase in risk for every 5 kg/m2 increase in BMI. Our laboratory has previously demonstrated that obesity is associated with increased colonic TNF‐α in parallel with elevated expression of tumorigenic Wnt‐signaling pathway target genes in a murine model. We hypothesized that the low‐grade inflammatory state associated with obesity also exists in human mammary tissue. Thirty‐one breast tissue samples were collected from women undergoing elective breast reduction surgery. Inflammatory cytokines (IFN‐γ, IL‐1β, IL‐2, IL‐6, IL‐8 and TNF‐α) were measured using a high‐performance, chemiluminescence immunoassay. A Pearson correlation was performed to determine the relationship between the expressions of those inflammatory cytokines and BMI. Among the 6 cytokines examined, the levels of IL‐1β, IL‐6 and TNF‐α, were positively associated with BMI (p‐values are 0.029, <0.001, and 0.032, respectively). This study demonstrated that overweight and obesity produced an inflammatory microenvironment in human breast tissue, which may promote the development of postmenopausal breast cancer. Further insights into how these cytokines mediate tumorigenic signaling pathways are needed.
Meeting Dietary Goals for Cancer Prevention by Age, Gender and Food Insecurity: Is Anyone Listening?
Authors: Spees Colleen , Hooker Neil , Clinton Steven , Taylor Christopher
Published: June 2021

Evidence‐based dietary recommendations have been developed for cancer prevention by several organizations including the American Institute for Cancer Research (AICR). Using data from 15,700 adults from 2005‐10 NHANES, we assessed concordance with the AICR dietary guidelines for Americans. Analyses of compliance was conducted for the total sample as well as stratified by gender, age groups (20‐30, 31‐50 and >50 years) and household food security status (fully, marginally, low, and very low). More than two‐thirds of food insecure adults were overweight (BMI>25). Females and those >50 years of age were significantly more likely to present with obesity (BMI>35, P<0.001). Less than 12% of all males and 20‐30 year olds met energy density goals (<125 kcal/100g of food, P<.001). Less than 8% all participants, regardless of age, gender or food security status consumed at least 3 oz. of whole grain or had at least half of their grains as whole grain. About 12% met recommendations for vegetable and fruit intakes, with lowest intakes among the males (P<0.01), 20‐30 year olds (P<0.001) and very low food secure (P<.001). Males (82%, P<0.001), adults >50 (65%, P<0.001), and the fully food secure (71%, P=.002) were less likely to meet sodium recommendations. Very low food secure (58%, P<.001) and young adults (63% of 20‐30y, P<.001) exceeded recommended alcoholic drinks per day (>1/day female, >2/day male). These findings underscore the poor level of adherence to dietary recommendations for cancer prevention in vulnerable subgroups.
Excess Body Weight Is Not Associated with Colorectal Cancer Survival: The Multiethnic Cohort
Authors: Maskarinec Gertraud , Harmon Brook , Ollberding Nicholas , Wilkens Lynne , Henderson Brian , Kolonel Laurence , Le Marchand Loic
Published: June 2021

Purpose

Excess body weight has been associated with a higher risk for colorectal cancer (CRC) and may also adversely affect mortality in CRC patients. The current study examined the relation of prediagnostic body mass index (BMI) with CRC‐specific and all‐cause mortality in the Multiethnic Cohort (MEC).

Methods

Among the 5 major ethnic groups, 4204 invasive cases of CRC were diagnosed between cohort entry and 2010. Cox regression was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI) while adjusting for relevant covariates. Using self‐reports at baseline and after 5.7±0.8 years (73% of participants), BMI was treated as time‐varying exposure.

Results

Of the 2258 men and 1946 women, 1674 (40%) were overweight and 939 (22%) were obese at baseline. After 6.0±4.7 years of follow‐up, 1976 overall deaths and 1095 deaths due to CRC occurred. No significant association with CRC‐specific mortality was detected in men (HR=0.94; 95%CI: 0.84, 1.04) and women (HR=0.98; 95%CI: 0.89, 1.08) per 5 units of BMI. In men, all‐cause mortality showed no relation with BMI (HR=0.97; 95%CI: 0.90, 1.06), whereas it was elevated in women (HR=1.10; 95%CI: 1.03, 1.31). Interactions of BMI with ethnicity were not significant, but risk estimates varied across groups.

Conclusions

Little evidence for an adverse effect of excess body weight on survival was detected within a multiethnic group of CRC cases although some variations in mortality were seen after stratification by sex and ethnicity.
Trefoil Factor Family 1 (TFF1) Inhibit the Invasion of Tumor Cells of the Pancreas
Authors: Yamaguchi Junpei , Kokuryo Toshio , Yokoyama Yukihiro , Nagino Masato
Published: June 2021

Objective

The tumor suppressive role of TFF has been recently reported in gastric tumorigenesis. Here we aimed to clarify the role of TFF1 as tumor suppressor in pancreatic tumorigenesis.

Methods

By immunohistochemistry, the expression pattern of TFF1 was analyzed in surgically resected specimen of PDAC (Pancreatic Ductal Adenocarcinoma; n=14), invasive IPMN (Intraductal Papillary Mucinous Neoplasms: n=12) and non‐invasive IPMN (n=10). Human pancreatic cancer cell line was treated by TFF1‐siRNA to evaluate the role of TFF1 in vitro.

Results

TFF1 expression is not found in normal pancreatic ductal epithelium. Pancreatic Intraductal Neoplasm (PanIN) has high expression of TFF1, suggesting that up‐regulation of TFF1 is the early event of pancreatic tumorigenesis. While TFF1 is also expressed in the intraductal compartment of PDAC and IPMN, it is frequently lost in the invasive compartment (50% (7/14) in PDAC and 58.3% (7/12) in invasive IPMN). The expressions of TFF1 in human pancreatic cancer cell lines were evaluated and Panc1 was found to have TFF1 mRNA. Suppression of TFF1 in Panc1 cells by siRNA does not change the proliferative rate of Panc1 cells; however, it was found to induce the higher invasive ability (55.2% of invasive area in control, 94.9% in TFF1‐siRNA; p<0.01) by Boyden chamber assay.

Conclusion

While acquisition of TFF1 seems to be the early event of pancreatic tumorigenesis, loss of TFF1 may result in the invasive transformation of pancreatic tumor.