bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimated Average 24‐h Urine Sodium Excretion in US Children
Authors: Pfeiffer Christine , Hughes Jeffery , Lacher David , Cogswell Mary , Wang Chia‐Yih , Johnson Clifford
Published: June 2021

In 2009–2010, US children aged 6–11 y and 12–19 y consumed an estimated average 2971 mg/d and 3563 mg/d of dietary sodium, respectively, which is above the 2010 Dietary Guideline of 2300 mg/d. To our knowledge, no nationally representative published data exist on urine sodium excretion in youth 6–19 y. We measured sodium levels in 306 spot urine samples of children 6–19 y participating in NHANES 2010. Due to the lack of calibration equations for children, we estimated 24‐h urine sodium (24hUNa) excretion by use of equations validated for adults living in the United States. Mean (SEM) estimated 24hUNa excretion was 2635 (127) mg/d and 2952 (72) mg/d for 6–11 y and 12–19 y old children, respectively. Estimated 24hUNa excretion was significantly higher among boys, 12–19 y olds, and overweight or obese youth, but did not vary by race‐ethnicity. The directions of the patterns in mean 24hUNa excretion by demographic group were the same as mean dietary sodium intake (based on one 24‐h recall). Spearman correlation between 24hUNa excretion and dietary sodium intake was weak (r=0.26, P=0.0001). Mean estimated 24hUNa excretion was >20% lower than mean dietary sodium intake among normal weight youth, non‐Hispanic white youth, 12–19 y olds, and girls. These differences may be a result of problems with the calibration equation or of misreported dietary intake. These 24hUNa excretion estimates from spot urine samples are consistent with dietary data and suggest that on average, US children consume too much sodium in relation to recommendations
Understanding Why Potential Shoppers Do Or Do Not Use Local Farmers Markets
Authors: Jensen Melissa , Alvarado‐Molina Nadia , Zuniga Marianela
Published: June 2021

Consumption of fruits and vegetables decreases risk of cardiovascular disease, some cancers, and other chronic diseases. Farmers markets (FM) can improve consumption of fruits and vegetables and contribute to community food systems. Governments enact policies to support FM, but FM in many communities are underused. Barriers often mentioned include inconvenient location, hours, and price, but research usually is conducted only with shoppers. We aimed to examine socio‐demographic characteristics, purchasing behaviors, and perceived motivators and barriers for potential FM shoppers. We surveyed 240 participants living within 1 kilometer of 2 FM so that inconvenient location was not a likely issue. Fifty‐six percent were FM shoppers, mostly female adults (mean age=50.6). FM shoppers had similar incomes but lower education than non‐shoppers. Fruits and vegetables were the most purchased products by shoppers (>90% of shoppers); other common items were meat, eggs and cheese (>30% of shoppers). Among shoppers, price, freshness, and close locality were main motivators to attend the FM. Among non‐shoppers, inconvenient hours of operation, lack of time, and high prices were reasons not to attend the FM. Qualitative data provided additional understanding of perceived strengths and weaknesses of FM. By understanding barriers and FM weaknesses for non‐shoppers, messages can be tailored to address these, leading to more effective social marketing strategies to promote FM usage. Our findings also provide FM managers with information on FM potential improvements, which will lead to our ultimate goal, an increase in the use of these markets as the main venue for fruit and vegetable purchase in the population.
Effect of a Family Based Intervention on Biomarkers of Diet Quality/Endogenous Metabolism and change in BMI z‐score
Authors: Matthan Nirupa , Xue Xiaonan , Gao Qi , Wylie‐Rosett Judith , Lichtenstein Alice
Published: June 2021

The objective was to assess the effect of a family‐based weight management intervention on biomarkers of diet quality/endogenous metabolism and cardiometabolic risk in children (7‐12 years; N=309) with baseline BMI z‐score (BMIz) >85th percentile. Families were randomized to a control (receiving standard care) or an experimental group (receiving targeted diet/physical activity strategies). Biomarkers were measured using GC or HPLC. After 1 year, significant decreases in BMIz (‐7%), LDL‐C (‐3%) and liver enzymes (‐3%) and increases in HDL‐C (2.3%) were observed in both groups, thus groups were subsequently combined. Among the dietary biomarkers, there were significant decreases in total trans (‐13%) and lutein (‐3%), and increases in omega‐3 fatty acids (18:3n‐3, 26%; 20:5n‐3, 16%; 22:5n‐3, 9%; 22:6n‐3, 7%). Using multivariate logistic regression (odds ratios per 10% increment in biomarker [95% CI]), total trans (1.2 [1.0‐1.4]), partially‐hydrogenated fat biomarker, lutein (1.1 [1.03‐1.13]) and lycopene (1.09 [1.03‐1.15]), egg and tomato‐based food biomarkers, were positively associated with change in BMIz. MUFA 16:1n‐7 (0.83 [0.72‐0.96]), indicator of de novo lipogenesis, was negatively associated, while stearoylCoA desaturase (1.53 [1.03‐2.26]), the rate limiting enzyme in MUFA synthesis, were positively associated with change in BMIz, respectively. Results suggest that foods high in trans fat and tomato‐based products (e.g., pizza) have an adverse effect on change in BMIz. Likewise biomarkers of in vivo metabolism were predictive of change in BMIz in this cohort of high‐risk children.
Plasma Metabolomic Profiles in Healthy Adults following Consumption of Broccoli Sprouts
Authors: Atwell Lauren , Clarke John , Hsu Anna , Bella Deborah , Choi Jaewoo , Stevens Jan , Pereira Cliff , Jiang Yuan , Dashwood Roderick , Williams David , Ho Emily
Published: June 2021

Sulforaphane (SFN), an isothiocyanate derived from cruciferous vegetables, has many potential health benefits including cancer prevention. There has been intense study of the molecular and genetic targets of SFN, however, there is limited knowledge around the biological pathways it targets in humans. This study's objective was to identify examine metabolomic profiles in healthy adult before and after consuming fresh broccoli sprouts, a rich and bioavailable dietary source of SFN, to observe how multiple metabolites respond to SFN consumption in vivo. Twenty healthy adults consumed 200 µmol SFN equivalents from fresh broccoli sprouts and provided blood samples at time 0, 3, 6, 12, 24 and 48 hours following consumption. Untargeted metabolomic analysis was performed on plasma samples from each time point using an AB Sciex TripleTOF® 5600 coupled to a Shimadzu ultra‐high performance liquid chromatography system. Following sprout intake, altered levels for metabolites associated with steroid, lipid and protein metabolism, the urea cycle, nucleotide and one‐carbon metabolism, and glutathione synthesis were observed. This research provides important information on novel molecular targets and mechanisms of SFN that can improve understanding of SFN's role in health and disease prevention. R01CA122906, P01CA090890, P30 ES000210
Impact of a Nutrition and Health Education Program on Obese Children
Authors: Weekley Arielle , Calkin Katie , Buffalo Julie , Boekel Susan , Mullis Rebecca , Anderson Alex
Published: June 2021

The purpose of this study was to evaluate the impact of the Health Matters for Families Program, which is a nutrition and health education intervention on the dietary and general lifestyle habits of obese children and their families. This was a prospective cohort study that enrolled clinically diagnosed obese children between 4 and 17 years of age. The intervention was individualized, conducted within a local pediatric office setting, and consisted of 6 face‐to‐face sessions of nutrition and health education for obese children and their caregivers. The intervention utilized culturally tailored materials, behavioral goal setting, and a multi‐component focus, which cumulatively targeted child‐centered goals. Our preliminary results show that participation in physical activity (蠅 30 minutes per day) improved from baseline measures. Fruit and vegetable consumption also improved; consumption of 2‐3 servings of fruit daily increased by 47.6%, while a similar trend was observed for vegetable consumption. The proportion of children drinking at least 4 cups of water daily increased by approximately 10%, while consumption of sugar‐sweetened beverages declined. No significant change was observed in BMI‐for‐age during the follow‐up. Findings from this study may have a significant public health impact by informing the development of effective interventions to address the current obesity epidemic and poor dietary habits of children from minority and low‐income households. Additionally, this project provides foundational knowledge for clinical and community health researchers to develop and implement obesity interventions targeting medical outcomes and lifestyle changes in children.
Effect of Prebiotic Fiber‐Induced Changes in Gut Microbiota on Adiposity in Obese and Overweight Children
Authors: Nicolucci Alissa , Hume Megan , Reimer Raylene
Published: June 2021

Childhood obesity has dramatically increased. Unfortunately, excess weight tends to persist into adulthood therefore therapies which target childhood obesity are essential in halting the obesity epidemic. Our objective was to determine if prebiotic fiber intake reduces body fat, pro‐inflammatory cytokines and insulin levels in overweight and obese children and to examine if this is due to a shift in gut microbiota composition. Overweight and obese children (蠅85th BMI percentile) aged 7‐12y (n=39) were randomized to consume 8g/day of prebiotic fiber (1:1 inulin:oligofructose) or equicaloric placebo for 16 weeks. Body fat (measured by dual‐energy X‐ray absorptiometry), pro‐inflammatory cytokines and insulin (quantified from fasted blood serum), and gut microbiota (quantified from stool) were measured at baseline and week 16. Statistical significance was determined using non‐parametric Mann‐Whitney U‐Test at p蠄0.05. The first cohort (n=13) have completed the study with the final n=26 to finish December 2014. There was a trend for prebiotic fiber to reduce trunk body fat compared to placebo (‐1.42% vs +0.37%; p=0.15). Waist circumference (‐2.22 vs +0.03 cm), interferon gamma (‐1.4 vs +2.1 pg/mL) and fasted insulin levels (‐53.6 vs +155.3 pg/mL) were reduced with prebiotic and increased with placebo but not significantly. Bifidobacteria abundance significantly increased with prebiotic (p=0.03). Prebiotic fiber is a potential non‐invasive treatment option to reduce body fat in obese and overweight children by gut microbiota modulation.

Funded by BMO Financial Group/Alberta Children's Hospital Research Institute and Canadian Institutes of Health Research.
Preference for Energy Dense Snack Foods in Healthy and Overweight Minority Preschool Children
Authors: Charvet Andrea , Brogan Hartlieb Kathryn , Yeh Yulyu , Jen K‐L Catherine
Published: June 2021

Snacking is an important eating episode for energy and development of food preferences in children. The purpose of this study was to describe the quality and quantity of snack intake in minority preschool children enrolled in the Head Start Program in four centers in Detroit, Michigan, and investigate differences by child weight status. This secondary data analysis used anthropometric and snack time food observation data from a convenience sample of 58 children (43% girls, 46±7.85 months old). BMI‐for‐age percentiles were used to separate children into weight categories according to CDC guidelines. Snack intake data (servings/snack) was converted into USDA food group portions and averaged for each child. Based on BMI‐for‐age percentiles, 70.7% of the sample was under/healthy weight and 29.3% was overweight/obese. Average snack time intakes of milk (0.74±0.33) and combined fruits/vegetables (0.77±0.33) were significantly lower than one USDA snack serving, while average intakes of energy dense foods such as grains (1.99±0.89), meat/meat alternates (2.20±1.91) and other foods (1.43±1.06) were significantly higher than one serving (p蠄0.05). Children ate more when offered canned fruits versus fresh fruits (0.93±0.57 vs. 0.65±0.37, p=0.007). Except for a significantly higher milk intake in the under/healthy weight group compared to the overweight/obese group (0.81±0.34 vs. 0.58±0.24, p=0.005], no relationship was found between snack food intake and weight category. A preference for energy dense foods was observed. Continued efforts should be made to provide nutrient dense foods at the preschool settings to promote healthier food habits.

AC support: NIH/NIGMS R25 GM061347
Connecting Early Life Undernutrition to Hearing Loss: Evidence from Nepal
Authors: Emmett SD , Schmitz J , Khatry SK , Wu L , LeClerq S , Karna S , Pillion J , West KP
Published: June 2021

Objective

Assess influences of early life undernutrition on young adult hearing loss in Nepal.

Design: Ear health was assessed in 2378 Nepalese young adults (14‐23 y) who as preschoolers participated in a 4‐monthly placebo‐controlled, randomized vitamin A (VA, 200,000 IU) supplement trial ('89‐'92). At baseline, children were measured for WT, HT and MUAC. Parents were queried about ear discharge at each visit. Sixteen years later, audiometry and tympanometry were performed, blinded to original supplement receipt. Hearing loss was defined as pure‐tone average>30dB (0.5,1,2,4kHz) and middle ear dysfunction (MED) as abnormal tympanometric peak height (<0.3‐>1.4mmho) or width (<50‐>110daPa). Children were classified as stunted (<‐2 HAZ) or wasted (<‐2 MUAC & <‐2 BMI‐for‐age Z).

Results: Hearing loss and MED affected 5.9% and 16.6% of subjects, respectively. Wasting was associated with odds ratios of 1.8‐2.2 for hearing loss and 1.4‐1.8 for MED, and stunting with ORs of 2.2‐1.7 for hearing loss, irrespective of MED (all 95% lower CL>1). For subjects with preschool ear discharge, VA receipt was protective against hearing loss, OR=0.58 (95% CI 0.37‐0.92). Further, we posit human antenatal VA deficiency may cause MED‐independent hearing loss (S Emmett, Med Hypotheses 2014;82:6), as reported in animals, similar to that associated with stunting.

Conclusion

Preventable early childhood and possibly fetal undernutrition, including VA deficiency, may predispose children to permanent hearing loss. Hearing loss should be considered a nutrition‐related public health burden.

Funded by Gates Foundation (OPP614)
Molecular Classification Predicts Outcome Among Patients With ER+/PR+/HER2‐ Breast Cancers
Authors: Sandhu Rupninder , Parker Joel , Anders Carey , Coleman William
Published: June 2021

ER+/PR+/HER2‐ breast cancers are frequently associated with good outcomes, but some patients experience progression/recurrence. We examined molecular subtypes of ER+/PR+/HER2‐ breast cancer to determine if molecular classification predicts patient outcome. Evaluation of gene expression patterns for 205 ER+/PR+/HER2‐ breast cancers enabled assignment of molecular subtype: 49% Luminal A (LumA), 27% Luminal B (LumB), 6% HER2‐enriched (HER2+), 3% Basal‐like (BL), 7% Claudin‐low (CL), and 8% Normal‐like (NL). Overall, 99/205 (48%) ER+/PR+/HER2‐ patients developed metastatic disease: 44/100 (44%) LumA, 29/55 (53%) LumB, 6/13 (46%) HER2+, 5/7 (71%) BL, 8/14 (57%) CL, and 7/16 (44%) NL. Among ER+/PR+/HER2‐ breast cancers, the average time to relapse for BL (27 months), HER2+ (25 months), and LumB (27 months) was significantly shorter than LumA (37 months). Kaplan‐Meier survival analysis did not reveal a significant trend between ER+/PR+/HER2‐ LumA versus LumB, HER2+, or CL subtypes, but the ER+/PR+/HER2‐ BL subset showed significantly worse relapse‐free survival (RFS) than the ER+/PR+/HER2‐ LumA subset (P=0.0444). Patients with ER+/PR+/HER2‐ BL breast cancer demonstrate 29% RFS at 50 months versus 56% at 100 months for ER+/PR+/HER2‐ LumA. Relapse among ER+/PR+/HER2‐ LumA breast cancers typically involved bone metastasis (80%), while ER+/PR+/HER2‐ BL breast cancers frequently metastasize to brain or lung (80%). Expression of gene signatures associated with aggressive molecular subtypes of breast cancer predict more aggressive disease among ER+/PR+/HER2‐ breast cancers.
Growth Monitoring and Promotion in Rural Ghana: Lack of Motivation or Tools?
Authors: Laar Matilda , Marquis Grace , Lartey Anna , Gray‐Donald Katherine
Published: June 2021

The effectiveness of growth monitoring and promotion (GMP) activities depend on the motivation and performance of nutrition educators. A 12‐mo capacity‐building intervention was carried out to improve identification and mitigation of child wasting. 30 community‐based GMP clinics in Upper Manya Krobo District, Ghana were randomized into: algorithm (A), length measurement (L), or control (C) groups. In A group, a simple algorithm based on predictors of wasting, helped community health workers (CHW) identify at‐risk children and provide tailored counseling. Length in addition to usual weight measurements allowed L group CHW to identify children with low weight‐for‐length. Standard‐of‐care was used in C group. Type of nutrition counseling given and caregivers' recall of nutrition messages were documented through direct observations of CHW and interviews with caregivers at monthly GMP sessions. About 30% of scheduled sessions were missed because of poor road conditions, disabled transportation, and scheduling conflicts. Out of the sessions held, only 60% provided individual counseling (IC). IC was not offered because of nurses' exhaustion, inadequate time due to late arrival of nurses and/or mothers, and caregivers' time complaints. 80% of observed caregivers recalled IC messages after one week; this did not differ by treatment. The proportion of GMP sessions and IC held was higher in A vs. C group (0.83 vs. 0.54 and 0.55 vs. 0.36, respectively; p< 0.01). GMP programs need mechanisms to motivate CHW to improve their effectiveness and mothers to improve their involvement in GMP. Having a clear, simple educational tool may provide needed support to improve GMP in Ghana. [Funded by IDRC and DFATD, Canada]
Do We Have The Wrong End Of The Stick On Reducing Undernutrition? Insights On Determinants Of Subnational Trends In India
Authors: Menon Purnima , Cyriac Shruthi , Kadiyala Suneetha
Published: June 2021

Background

Studies of national trends in undernutrition have identified underlying determinants (education, sanitation, poverty, food security) as key drivers of change. We aimed to understand the role of immediate & underlying determinants of subnational trends in underweight between 2002 & 2011 in India.

Data

We constructed a district‐level dataset from 2 surveys, 9y apart, of children <5y in 100 poor districts in India, using variables common across surveys & including additional variables from other district data sources. Outcome variable: percent change in district‐level prevalence of underweight (weight‐for‐age <‐2 z‐scores) between 2002 & 2011 (stunting trend data not available). Regressions included variables capturing immediate and underlying factors & initial underweight levels.

Results

Mean underweight decline was 15.10±12.10 pp. Improvements in maternal education (p<0.1), household assets (p<0.05), access to toilets (p<0.05), household diet quality (% of food expenditures spent on cereals) (p<0.001), poverty (share of food expenditures out of total) (p<0.001) & rural roads (p<0.1) were associated with underweight declines (R2=0.83). Change in immediate determinants (breastfeeding, immunization & diarrhea) was not associated with declines, possibly due to poor measurement or an incomplete set of available determinants.

Conclusions

Our results point to improvements in social equity‐related factors as primary drivers of nutrition change in poor areas. They also highlight a need to invest in better integrated datasets for robust analysis of the balance of immediate and underlying determinants. Funding: UKAID, through Transform Nutrition, led by IFPRI.
Infant nutritional outcomes in an integrated agriculture, health and nutrition program in Western Kenya
Authors: Webb Girard Amy , Wanjala Rose , Okuku Haile , Levin Carol , Cole Donald , Low Jan , Grant Frederick
Published: June 2021

The Mama SASHA project integrated an orange‐fleshed sweetpotato (OFSP)‐focused, agricultural‐nutrition education intervention into delivery of routine health services and pregnant women's clubs. It aimed to improve diets, nutrition and health of pregnant /lactating women and their infants. We enrolled 505 women from intervention and control facilities during first antenatal care visit in early pregnancy. Infant anthropometry, vitamin A and iron status were assessed at 4 and 9 mos of age and anemia at 9 mos. There were no significant socioeconomic differences at enrollment. OFSP consumption was significantly higher and maternal MUAC significantly lower in intervention mothers at enrollment and throughout the follow up period. Mean birth weight was 3.27±0.5 kg and did not differ between groups. At 9 mos household food security and coverage with VA supplementation were significantly higher in controls; consumption of OFSP was significantly higher in intervention infants. From 4 to 9 mos postpartum, stunting increased significantly in controls (6.9% to 10.6%, p<0.05); stunting decreased nonsignificantly in the intervention group (11.5% to 10.3%, p>0.05). There was no change in either underweight from 4 to 9 mos (intervention: 3.1% to 3.3%; controls: 3.9% to 4.3%) or wasting (intervention: 2.1% to 1.6%; controls: 2.9% to 2.7%). There were no significant group differences in infant micronutrient status or anemia at 4 or 9 months. Further analysis will evaluate impact using mixed models that control for clustering, repeated measures and confounding.
Your Role in Meeting LCME Accreditation Standards
Authors: Barzansky Barbara
Published: June 2021

The Liaison Committee on Medical Education (LCME) accredits educational programs leading to the MD degree. LCME accreditation provides assurance of educational program quality to medical educators, medical students, and the public. Many of the LCME's standards are directly relevant to the teaching and assessment done by anatomy faculty members. This session will discuss the LCME's expectations for some key standards that are commonly cited during reviews of medical schools and describe how anatomy faculty can assist their schools in achieving and maintaining compliance.
The End of an Old Dogma with Crucial Implications for Medical and Biology Students and for Medicine: regenerative, Developmental, Paleontological and Evolutionary Studies Contradict the Fore‐hindlimb Serial Homology
Authors: Diogo Rui , Ziermann Janine
Published: June 2021

Most evolutionary and medical textbooks state that the tetrapod fore and hindlimb are serial homologues. Here we show how regenerative studies of axolotls, developmental studies of tetrapods, and comparative and evolutionary studies of all major vertebrate groups, including recent re‐analyses of the appendicular muscles of chondrichthyans, dipnoans and coelacanths contradict this old dogma. The integrative analysis of the data available strongly supports the idea that the similarity of the muscles and bones of the fore and hindlimbs of tetrapods such as salamanders and modern humans is not due to serial homology, but is instead the result of independent evolutionary changes (homoplasy) occurred mainly during the origin of tetrapods due to the co‐option of similar genes for the development of both limbs. It also offers new insights about the ancestral Bauplan and morphogenetic gradients of tetrapod limbs, including the striking similarity of the zeugopodial (forearm/leg) and autopodial (hand/foot) muscles of the two limbs and ventro‐dorsal symmetry of the zeugopodial muscles of a same limb, about the marked differences between pelvic and pectoral girdle structures, the homeotic transformations related to the number/identity of the digits and associated soft tissue changes, and the differences between limb ontogeny and regeneration, and about limb birth defects and their crucial medical implications.
Vision‐Based Spatial Abilities and Pictures of Objects Recognized from Haptic Perception
Authors: Langlois Jean , Dagenais Yvan , Martin Marcel , Lemieux Renald , Lecourtois Marc , Yetisir Elizabeth , Bellemare Christian , Bergeron Germain , Hamstra Stanley , Wells George
Published: June 2021

Objective. As a basis for an application in anatomy education, vision‐based spatial abilities have been previously correlated with a drawing score based on haptic perception of objects. The objective of the current study was to determine whether a picture could replace a drawing in correlating haptic perception of objects with vision‐based spatial abilities tests.

Methods. A cohort of 48 medical graduates was enrolled in a prospective study. Spatial abilities were measured with a redrawn Vandenberg and Kuse Mental Rotations Tests in two (MRTA) and three (MRTC) dimensions and a Surface Development Test (SDT). Twenty‐five objects constructed from various shaped parts glued together were identified on a picture by participants after haptic perception. The maximum score was 24 for each of MRTA and MRTC, 60 for SDT, and 25 for the picture score. Descriptive statistics included median and lower and upper quartiles. Spearman's correlation coefficient was used to compare the picture score to MRTA, MRTC and SDT scores.

Results. The picture score [18 (12, 21)] was correlated with MRTA [14 (9, 17)], MRTC [9.5 (6.5, 12)] and SDT [44.5 (36, 53)] scores with a correlation of 0.427 (p = 0.0025), 0.539 (p < 0.0001) and 0.429 (p = 0.0024), respectively.

Conclusions

Vision‐based spatial abilities tests were correlated with pictures of objects recognized from haptic perception. Individual differences in spatial abilities as related to haptic perception have implications for education in the anatomy laboratory.

This study was supported by an internal grant from the Department of Surgery, University of Sherbrooke, Sherbrooke, QC, Canada.
Activation of RANKL and MMP Production by Endothelin Signaling in Cultured Periodontal Fibroblasts
Authors: Ruest L Bruno , Ranjbaran Hamid , Tong Eric , San Miguel Symone , Svoboda Kathy
Published: June 2021

Periodontitis is a group of inflammatory diseases that affect the tissues surrounding and supporting the teeth. These diseases progressively cause the loss of the alveolar bone and the periodontal ligaments, which can lead to dental exfoliation. Endothelin signaling via the activation of the endothelin‐A receptor (Ednra) by endothelin‐1 (Edn1) is a pathway that may play a role in the disease since the expression of the receptor and ligand is elevated in the periodontal tissues of patients with periodontitis. Using cultured primary periodontal fibroblasts (HPFs), we investigated whether Ednra activation by Edn1 alters the expression of factors involved in the destruction of the periodontium. HPFs were obtained from the extracted teeth of consenting healthy non‐smoking patients with institutional board review approval. The HPFs were treated with 20 and 100nM Edn1for 6 and 24 hours. The osteoclast‐activating factor RANKL and members of the matrix metalloproteinase (MMP) family were examined by western blotting. Edn1 treatment stimulated the production of MMP1, MMP8 and RANKL in a dose‐ and time‐dependent manner; blocking Ednra function with the specific antagonist TBC3214 inhibited the response. Stimulation of Ednra by Edn1 activated phospholipase C. In turn the enzyme activated the ERK MAP kinase‐dependent pathway to increase the MMP1 protein levels, and also activated an independent pathway for RANKL, likely involving NFAT activity. These results support the theory that endothelin signaling, <em style=”mso‐bidi‐font‐style: normal; via the activation of Ednra, stimulates the destruction of the periodontal tissues associated with periodontitis by promoting the expression of MMPs and RANKL.
Chemical Tools for Studying the Activation of the Intracellular Innate Immune Protein Nod2
Authors: Grimes Catherine , Melnyk James
Published: June 2021

Chronic inflammatory disorders, such as Inflammatory Bowel Disease, arise from an inappropriate immune response to bacteria. In order to treat these diseases, we need a better understanding of how the innate immune system senses and responds to bacteria. It has long been known that muramyl dipeptide (MDP,Figure 1), a fragment of bacterial cell wall (peptidoglycan), is able to generate an immune response. Recently, it has been shown that the intracellular, mammalian protein Nod2 is involved in sensing the presence of MDP in the cell, leading to activation of the synthesis of inflammatory molecules. Nod2 is an important protein to human health, as mutations in the gene have shown an increased incidence of Crohn's disease.

The mechanism of activation of the Nod2 signaling pathway by MDP is not understood. For example, it is not known if MDP directly interacts with Nod2. We have taken a chemical biological approach to this problem by synthesizing tagged versions of MDP. This tool was then utilized to probe for an interaction between Nod2 and MDP. We describe the development of a variety of binding assays and present a model for Nod2 activation via MDP. Our approach has led to a deeper understanding of the biophysical mechanisms used by the innate immune system to sense bacteria.
Quaternary Structure Dynamics in Allostery ‐Aapplication to Mammalian Phenylalanine Hydroxylase
Authors: Jaffe Eileen
Published: June 2021

There are an increasing number of proteins for which architecturally distinct homo‐multimers are implicated in alternate functions (e.g. porphobilinogen synthase, Ebola VP40, PKM2, glutaminase C, HMG CoA reductase, mechanosensitive ion channels, glucosamine‐6‐P synthase, HIV integrase), though the mechanism for multimer interconversion is often not well understood. Detailed analysis of porphobilinogen synthase suggests generalizations that can be applied to deciphering allosteric mechanism for other homo‐multimeric proteins, particularly those whose characteristics are consistent with the morpheein model of protein allostery. These characteristics are: 1) the difference between high‐activity and low‐activity multimers depends on inter‐subunit interactions that modulate active site access; 2) the pathway for multimer dissociation can expose large surface areas; 3) the conformational change that dictates assembly to architecturally distinct multimers is a hinge motion between domains of each subunit; 4) many single amino acid substitutions throughout the protein can change the intrinsic equilibrium between alternate multimers, with implication for understanding disease; 5) the position of the quaternary structure equilibrium responds to environmental factors such as pH, temperature, ionic strength, and small molecule ligand binding to multimer‐specific sites; 6) there are phylogenetic variations in sampling components of the quaternary structure equilibrium. In the context of a full‐length X‐ray crystal structure of mammalian phenylalanine hydroxylase, these principles are applied to deciphering allosteric regulation within the family of aromatic amino acid hydroxylases.
Metabolic Complexity of Aggressive Primary and Metastatic Brain Tumors Beyond the Warburg Effect: What Substrates are Fueling the Citric Acid Cycle?
Authors: Maher Elizabeth
Published: June 2021

Background

Glioblastomas and brain metastases are aggressive, highly proliferative tumors with short survival times. 13C‐NMR analysis of resected tumors from brain tumor patients infused with 13C‐glucose at the time of surgery established that oxidation of glucose was occurring simultaneously with high lactate production. While it was clear that the citric acid cycle was actively metabolizing glucose, there were carbons in the acetyl‐CoA pool that could not be attributed to infused 13C‐glucose. The tumors were metabolizing another substrate(s), identified as the 'substrate gap' (Maher et al., 2012). Since astrocytes, the presumptive cell of origin of glioblastomas, use acetate as a major energy substrate, we investigated whether the tumors were capable of oxidizing acetate. Brain metastases, tumors derived from organs that do not normally oxidize acetate were studied to determine whether altered substrate choice is cell type dependent or a property of brain tumors. Methods: For these studies we used our human orthotopic tumor mouse models of glioblastoma and brain metastases from non‐small cell lung cancer, breast cancer, renal cell carcinoma, melanoma and endometrial cancer, which have remarkable fidelity to the human tumor from which they were derived. The orthotopic tumors are passaged in the brain, without adaptation to culture. We co‐infused [1,2‐13C]acetate and [1,6‐13C]glucose for 2 hours in tumor‐bearing mice and then analyzed the resected tumor by 13C‐NMR. In addition, we infused [1,2‐13C]acetate in patients during surgery after obtained informed consent on an IRB‐approved protocol. The 13C‐NMR results from the resected tumors were compared to the prior human studies of infused 13C‐glucose and to the results in the orthotopic mice. Results: The orthotopic tumors from the glioblastomas and brain metastases all have the capacity to oxidize acetate and do so simultaneously with glucose oxidation. We have validated this finding in patients with glioblastoma and brain metastases.

Conclusions

Together the data demonstrate a strikingly common metabolic phenotype in these diverse brain tumors that includes the ability to oxidize acetate in the citric acid cycle. It is unclear at present whether this represents an adaptation to meet the high bioenergetic demands of growth in the brain, is a general characteristic of metastatic tumors, or a basic feature of malignant transformation. Evaluation of human primary tumors in vivo will help to address this question.
Metabolomics by mass spectrometry based molecular networking and spatial mapping
Authors: Garg Neha , Conrad Douglas , Dorrestein Pieter
Published: June 2021

Direct measurement of metabolites from diseased tissue remains a challenge owing to structural diversity of the large number of primary and secondary metabolites present. These metabolites represent the climax of all physiological responses and reflect ecological relationships between pathogenic microbes and human response. Strategies aiming at direct measurement of metabolites will enhance our understanding of the roles that these molecules play and may result in emergence of new molecules and novel biosynthetic pathways. Untargeted metabolomics employed for such studies generates large volume of datasets that are rich in information hampering comprehensive analysis. Recent advancements in mass spectrometry and bioinformatics tools have reinvigorated the field of untargeted metabolomics of complex samples. Herein, we employ high‐scan‐speed QTOF coupled with ultra high performance liquid chromatography for data collection combined with molecular networking as organizational tool, cytoscape and spatial mapping as visualization tool, and automated database search for rapid identification of metabolites. A suite of microbial metabolites, bioactive lipids, sterols, fatty acids, polysaccharides, and drugs were identified from direct tissue extractions of human lung associated with cystic fibrosis and their distributions were plotted in 3D and correlated with distribution of microbiome in the lung.
Genetic Control of Immune Variation across the Human Population
Authors: Hacohen Nir
Published: June 2021

A focus of our work is to develop systems‐level approaches to dissect the innate immune response to pathogens in dendritic cells, focusing on the pathway from receptor engagement to gene expression. An important dimension that is not well understood is the impact of inter‐individual genetic variation on pathogen responses, especially in the context of common diseases. Using a combination of experimental and computational approaches, we determined the quantitative effects of genetic variation on gene expression in response to viruses and bacterial ligands in human dendritic cells. We identified thousands of common cis genetic variants associated with gene expression after stimulation with E. coli lipopolysaccharide, influenza or IFNβ. We used promoter reporter assays and genome editing to localize and validate causal variants to binding sites of pathogen‐activated STAT and IRF transcription factors. We also identified a variant in IRF7 that is associated in trans with the type I interferon response to influenza virus. Many of the cis and trans variants are also known disease variants, suggesting how DC innate sensing may contribute to immune‐related diseases. Finally, we identified a class of genetic variants that affect splicing, cluster near known splice sites and overlap with GWAS loci at the same frequency as variants that affect expression. Our results reveal common alleles that explain inter‐individual variation in pathogen sensing and impact susceptibility to immune‐mediated diseases.
Effect of the Intake of High‐SDS Product on Metabolic and Inflammatory Markers in Healthy Subjects with High Metabolic Risk
Authors: Meynier Alexandra , Lambert‐Porcheron Stéphanie , Normand Sylvie , Roth Hubert , Laville Martine , Vinoy Sophie
Published: June 2021

Objectives

The comparison of metabolic and inflammatory responses following the ingestion of cereal products high in Slowly Digestible Starch (SDS) was studied in subjects with impaired glucose tolerance.

Methods

In a cross‐over design, 20 (13F/7M) healthy overweight subjects with high metabolic risk participated to 3 sessions: one session testing a glucose solution (54g which is the amount of carbohydrates provided by the two other breakfasts), two sessions testing either a biscuit high in SDS or a rusk without SDS with 250 mL of semi‐skimmed milk and a hot beverage. The 2 sessions with cereal products followed a 3‐week period where the corresponding cereal product was daily consumed. Glycemia, insulinemia, blood lipid profile and markers for inflammation and oxidative stress were followed during a 240‐minute postprandial period.

Results

Glycemic responses following both cereal products were lower compared to glucose solution. iAUC(0‐120 min) glycemia was significantly lower (‐32 %) following the breakfast with biscuit high in SDS compared to rusk without SDS. The insulinemic response was also lower following the breakfast with the biscuit compared to the 2 other sessions. No significant difference was observed between the 2 groups with cereal products for blood lipid profile and for the makers of inflammation and oxidative stress.

Conclusion

Breakfast with a high‐SDS biscuit led to lower glycemic and insulinemic responses compared to breakfast including a rusk with no SDS in subjects with high metabolic risk. The ingestion for 3 weeks of the cereal products did not modified fasting and postprandial markers of inflammation and oxidative stress.
Grape Seed Extract Enhances Jejunum Epithelial Differentiation likely through Suppressing Inflammation in IL10‐/‐ mice
Authors: Bibi Shima , Kang Yifei , Du Min , Zhu Mei‐Jun
Published: June 2021

The epithelium of small intestine is constantly renewing, which requires rapid proliferation and differentiation of epithelial cells, a process impaired in the gut with inflammatory bowel disease (IBD). Grape seed extract (GSE) is a natural polyphenolic mixture that possesses anti‐inflammatory effects. In this study, 6‐wk‐old interleukin10‐ deficient (IL10‐/‐) mice were supplemented with GSE (0 or 0.1%) through drinking water for 12 weeks, then the jejunum tissues were collected for the analyses of differentiation and inflammation markers. GSE supplementation resulted in increased jejunal villus height and mucosal length, and enhanced goblet cell density, indicating an enhanced epithelial differentiation. Consistently, the mRNA expression of differentiation related markers including villin, aminopeptidase and glucose transporter‐2 were increased in GSE supplemented jejunum, so did two key differentiation transcription factors, Hairy/Enhancer of Split 1 (Hes1) and Krüppel‐Like Factor‐4 (KLF4). IL10‐/‐ mice are known for enhanced inflammatory response, while inflammation impairs gut epithelial differentiation. Thus, we speculated that improved differentiation in jejunum of IL10‐/‐deficient mice probably due to its anti‐inflammatory activity. Indeed, GSE supplement down‐regulated TNF‐α, and IFNγ expression and thus regulated NF‐κB signaling. Unexpectedly, GSE reduced intestinal alkaline phosphatase activity. In conclusion, GSE promotes jejunum epithelial differentiation in IL10‐/‐ mice, which was likely due to its anti‐inflammatory effect (NIH R15HD073864).
Acute Effect of Cinnamon Extract and Ground Cinnamon on Blood Glycemic Response in Overweight Healthy Volunteers
Authors: Jiang T Alan , Tijuana Moss‐Pierce Tijuana , Li Qian
Published: June 2021

Accumulating evidence has suggested that cinnamon has beneficial effects on glycemic control. Studies have indicated that the glucose lowering effect of cinnamon extract is superior to ground cinnamon. The objective of this study was to compare the effects of cinnamon extract (CE) added to instant oatmeal on postprandial glycemic response and insulin levels relative to ground cinnamon (GC) and a placebo control. Eight overweight male adults (ranged from 19 to 40 y) received four diets‐containing 50 g available carbohydrate from instant oatmeal in random order: (plain oatmeal; oatmeal + 3 g GC; oatmeal + 3 g CE; and oatmeal + 6 g CE). The total polyphenol content in 3 g CE and GC was the same. Blood glucose concentrations, the main outcomemeasure, were assessed at 0, 30, 45, 60, 90, 120, 180, 240 and 360 min. The incremental area for plasma glucose response curves (iAUC) was calculated using GraphPad Prism 6, ignoring the area below the baseline (0 min) concentration. The addition of either 3g or 6g CE to the oatmeal significantly reduced both 0‐180 min and 0‐360 min plasma glucose iAUCs (P<0.05), lowering plasma glucose iAUC by 56% between 0 and 180 min compared to the control. However, glucose iAUC was not significantly reduced in 3g GC treatment compared to the control. There were no significant differences in plasma insulin iAUCs between the diets. These results suggest that CE may be more effective than the equivalent amount of GC in moderating postprandial glucose response in overweight adults. ClinicalTrials.gov Identifier: NCT01847053. This research was supported by McCormick and Company, Inc.
Development of a Formal Protocol to Map the Community Food Environment Using Direct Observation: a Case Study in Urban Guatemala
Authors: Garcia Rosario , Kanter Rebecca , Fuentes Déborah , Burgunder Lauren , Scieszka Laura , Díaz Ruiz Elena , Andringa Sygrit , Browne Lauren , Polanco Ana , Solomons Noel
Published: June 2021

Background

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

Objective

To develop a formal protocol to improve the reliability of using direct observation to map the food environment in Guatemala.

Methods

Four teams of two raters were asked to walk two thoroughfares in urban Quetzaltenango, Guatemala. Each team consisted of one rater from Guatemala and one non‐Guatemalan. All teams read the mapping protocol and explored the area prior to mapping. Data was collected in a step‐wise fashion. The first team collected data and revised the mapping protocol that was then utilized by the next team. The validity of direct observation in mapping a community food environment in Quetzaltenango was determined by comparing the inter‐team concordance on each subsequent use of the protocol; and compared to data previously collected without a protocol.

Results

The inter‐team reliability improved with the use of a formal protocol and mixed‐ethnicity teams. On one street, the inter‐team reliability improved to 76% using the revised protocol from 67% with the original protocol; compared to 60% without a protocol. On the other street in which 40% of the food establishments were mobile vendors, the improvement in inter‐team reliability was modest.

Conclusions

In Guatemala, street‐mapping correspondence saturates at a certain point with or without considering the ambulatory aspects of carts and street vendors. A formal protocol and mixed teams that include a rater native to the country of interest improve the use of direct observation as a reliable low‐cost method to map the community food environment.
Glycemic Index and Glycemic Load and Liver Enzyme Activity
Authors: Chiavaroli Laura , Augustin Livia , Ireland Christopher , Mirrahimi Arash , Sievenpiper John , Kendall Cyril , Jenkins David
Published: June 2021

Objective

The relationship between non‐alcoholic fatty liver disease (NAFL) and insulin resistance, suggests that dietary interventions to reduce postprandial glycemia and insulin demand, i.e. low glycemic index (GI) and low glycemic load (GL) diets, may be relevant to NAFL.

Methods

Liver enzymes (ALT and AST) were measured in two 3‐month clinical trials of low GI or GL versus control (high cereal fiber) diets in participants with type 2 diabetes (n=212). Baseline liver enzymes were also measured in three additional studies of type 2 diabetes (n=299).

Results

In study 1, the low GI diet resulted in significant reductions in both liver enzymes with a greater reduction for AST when compared to the control diet (P<0.05). In study 2, the low GL diet demonstrated significant reductions in both liver enzymes, while the control diet significantly reduced AST. However, the reductions in AST were significantly greater on the low GL diet compared to control (P<0.05).
Using baseline data from studies 1 and 2 as well as 3 additional studies, baseline correlations between liver enzymes and markers of metabolic syndrome revealed significant positive correlations for both AST and ALT with diastolic blood pressure and with triglycerides, and for ALT with fasting glucose, HbA1c and systolic blood pressure (P<0.05). Of the dietary factors correlated with liver enzymes, only dietary cholesterol was positively associated with AST and ALT (P<0.05).

Conclusion

Lower GI and GL diets improved liver enzymes and thus may play a role in reducing the risk of NAFL.
Funding: Barilla
An updated analysis of trans fatty acids in Canadian packaged foods
Authors: Schermel Alyssa , Arcand JoAnne , Kutlesa Daniela , Jefferson Katherine , L'Abbe Mary
Published: June 2021

The Canadian food industry has voluntarily reduced the trans fatty acid (TFA) content of foods, however there are no updated analyses of TFA levels in Canadian foods. This study assessed TFA levels in Canadian packaged foods in 2013, compared to historical data. Data from Health Canada's Trans Fat Monitoring Program (TFMP, n=541 in 2006‐09) and the University of Toronto Food Label Information Program (n=1999 in 2010; n=2542 in 2013) were used. In 2013, 97% of foods met the TFA limits, increased from 95% in 2010 and 78% during the TFMP. The proportion of products meeting the TFA limits was below the overall average for lard (0%), coffee whiteners (67%), brownies (88%), snack puddings (92%) and garlic bread (94%). Among food categories with >10% of products exceeding TFA limits in 2010, there were few significant increases in the proportion of foods meeting TFA limits in 2013 compared to 2010, including dairy free cheeses (0% to 83% meeting, p=0.002) and cakes with pudding/mousse (77% to 97%, p=0.046). When assessing TFA as a percent total fat, Mexican kits was the only category with a significant increase in mean TFA as a percent total fat (7.6±1.8% to 20.3±5.9%). Categories exceeding 20% TFA as a percentage of total fat were coffee whiteners (55.6±16.7%), frosting (23.1±9.7%), lard and shortening (22.0±17.8%), margarine (20.5±14.4%) and popcorn (37.5%). There has been an overall improvement in the proportion of packaged food products that meet the recommended TFA limits and the majority of food categories did not have increased levels of TFA. However, several categories continue to have an unacceptably high proportion of foods exceeding TFA limits, suggesting that action by the food industry and/or government is still required to ensure maximal health benefits for Canada.