bluuebunny/crossref_metadata_2025 huggingface dataset:
Oils rich in alpha‐linolenic acid independently protect against characteristics of fatty liver disease in the delta‐6‐desaturase null mouse
Authors: Monteiro Jessica , McLennan Mira , Hillyer Lyn , Askarian Fatemeh , Moghadasian Mohammed H. , Nakamura Manabu T , Ma David W.L.
Published: June 2021

Non‐alcoholic fatty liver disease (NAFLD) is a growing health concern. The study objective was to use the novel Δ‐6‐desaturase null (D6KO) mouse to determine if α‐linolenic acid (ALA) can independently prevent hepatic steatosis and inflammation. Experimental groups include male wild type (WT) or D6KO mice fed a high fat diet (30% fat) containing either: lard (LD), canola oil (CD,11% ALA), flax oil (FD,50% ALA), or fish oil (MD, n‐3 HUFA) (n=4–7/group) for 8 or 20 weeks. At 8 weeks mean hepatic inflammation scores for D6KO CD and FD groups were intermediate between LD and MD scores, and lower than WT scores. In contrast, D6KO FD and CD groups had higher hepatic steatosis scores relative to WT mice. FD and MD D6KO groups had lower liver lipid mass relative to LD‐fed D6KO mice. Similar trends were seen at 20 weeks. Gas chromatography confirmed the absence of n‐3 HUFA (LD, CD, FD) and of enrichment ALA (CD, FD) in D6KO liver tissue. Results confirm that perturbations in essential fatty acid metabolism lead to the development of fatty liver, and suggest that oils rich in ALA can independently prevent hepatic inflammation. Supported by Canola Council of Canada, NSERC, CFI/ORF to D.Ma and OGS to J. Monteiro

Grant Funding Source: Canola Council of Canada, NSERC
Diets that follow the 2010 Dietary Guidelines for Americans (DGA) are associated with higher intakes of nutrients of concern
Authors: Troy Lisa M. , Jacques Paul F.
Published: June 2021

We updated the Dietary Guidelines for Americans Adherence Index (DGAI) to reflect changes between the 2005 and 2010 DGA. The DGAI_2010, a continuous score (range 0–100), measures adherence to the key dietary recommendations of the 2010 DGA. General linear models adjusted for age, sex, and energy intake were used to examine cross‐sectional associations between DGAI_2010 median scores across quintile categories and continuous measures of nutrients of concern (calcium, vitamin D, potassium, dietary fiber) identified in the 2010 DGA in 1562 men and 1768 women of the Framingham Offspring Study. DGAI_2010 median scores were 87.0 in the highest quintile category and 19.7 in the lowest. Subjects in the highest DGAI quintile category were more likely to be women, non‐smokers, older (56.8 vs 52 years), have a lower BMI (26.9 vs 28.1) and had significantly (p<0.0001) higher dietary intakes of all four nutrients than subjects in the lowest quintile category (i.e., calcium 879 vs 646 mg/d; vitamin D, 6.2 v. 3.8 mcg/d; potassium, 3.6 vs. 2.5 g/d; fiber, 13 vs. 7 g/1000 kcal/d). However, the mean intakes of the subjects in the highest quintile category were still below the Dietary Reference Intakes. Including dietary supplements increased intakes of calcium (1009 vs 697 mg/d) and vitamin D (9.6 vs. 5.9 mg/d). It may be difficult to meet requirements for shortfall nutrients in the face of such low DGA compliance without supplementation.
Exploring the landscape of nutrition related marketing in Canada: is it guiding consumers to more healthful dietary patterns?
Authors: Sacco Jocelyn , Tarasuk Valerie
Published: June 2021

A majority of Canadians report that they use food labels to obtain nutrition information and make food purchasing decisions. However, apart from the nutrition facts table, this information appears at the manufacturer's discretion. It is unclear whether the current landscape of Nutrition Related Marketing (NRM) on foods functions to promote healthy eating. Our objectives were to examine which foods are taking up NRM, what is being communicated to consumers, and what the implications of this practice are for population health. Front‐of‐package (FOP) NRM was recorded from all packaged foods (n=20520) in 3 large grocery stores in Toronto, representing the top three food retailers in Canada. Descriptive statistics were used to estimate the proportion of foods with NRM by food category and type of claim. 39% of all products had FOP NRM. It was especially prominent among beverages, cereals, snacks, and yogurt. Claims for the absence of undesirable nutrients (e.g. trans fat) were 1.5 times as common as claims for the presence of desirable nutrients (e.g. vitamin C). Claims for nutrients with a high prevalence of suboptimal intakes in the population (e.g. sodium, vitamin D, magnesium, and fibre) were found infrequently, even among foods able to bear these claims. FOP NRM is widespread in Canada, yet this practice provides limited nutritional guidance. This project is supported by CIHR.
Nutrition related health status of individuals affected by coal and tobacco economies and policies in Virginia
Authors: Meacham Susan L , Sukpraprut Suport
Published: June 2021

To assess the effects of mining on community well‐being a comparative study assessed the nutritional health of individuals in Virginia targeting regions typically characterized by more health disparities than other regions of Virginia. The Preventive Medicine Research Center at Via College of Osteopathic Medicine‐Virginia Campus (VCOM) conducted the study with physicians and medical residents in OMNEE (Osteopathic Medical Network of Excellence in Education). Selected for study were counties where mountaintop mining is currently a primary source of employment; as well as counties considered non‐coal‐mining, historically coal‐mining, and tobacco producing. Groups were comparable in subject number and matched by socioeconomic status, i.e., poverty, education, unemployment, race/ethnicity, etc. Data collected through local health department and medical records were analyzed on individuals as was secondary data from state and national data sources. Primary outcome measures were reported for chronic diseases, i.e., heart, cancer, kidney, stroke, asthma, lung, obesity, diabetes, thyroid, hypertension, and birth defects.

Funding: Appalachian Research Initiative for Environmental Science, Directed by the Virginia Center for Coal and Energy Research, Virginia Tech, Blacksburg, VA
MICROBIAL COLONIZATION PATTERNS OF PIGLETS FED BOTH SOW MILK AND FORMULA IS MORE SIMILAR TO THAT OF EXCLUSIVELY SOW‐REARED THAN FORMULA‐FED PIGLETS
Authors: Wang Mei , Radlowski Emily C. , Li Min , Monaco Marcia H. , Donovan Sharon M.
Published: June 2021

By 6 months, ~30% of U.S. babies receive both breastmilk and formula (combined feeding; CF), but little is known about its effect on microbial colonization, particularly in the presence of prebiotics. Newborn piglets were randomized into 5 groups: FF, FP, SR, CF and CP (n=6 per group). Sow‐reared (SR) remained with the sow 24h/day and formula fed (FF) or FF + prebiotic (FP; 4:1 galactooligosaccharide and inulin) were fed a milk replacer. CF and CF + prebiotic (CP) piglets were sow‐reared for 5d and were then rotated between the sow and formula every 12h. On d21, ascending colon contents were collected. Microbiota was assessed by pyrosequencing and denaturing gradient gel electrophoresis (DGGE). Distance‐based redundancy analysis of DGGE and pyrosequencing data separated FF and FP from SR, CF and CP. CP differed from SR by both methods, while CF tended (p=0.06) to differ from SR by DGGE, but not by pyrosequencing. No differences in microbiota between FF and FP or CF and CP were found. Indicator species analysis showed that SR harbored more Resoburia and Actinobacillus, FF/FP had more Weissella and Enterococcus and CF/CP more Megasphaera and Prevotella. Thus, the three feeding paradigms produced distinct microbial colonization patterns; however, CF was more similar to exclusively SR than FF. Adding prebiotics to FP or CP did not result in colonization patterns more similar to that of SR (BMS Freedom to Discover Award).

Grant Funding Source : Bristol‐Meyer‐Squibb
Human Milk Oligosaccharides and Postnatal Transmission of HIV through Breastfeeding
Authors: Kuhn Louise , Kim Hae-Young , Hsiao Lauren , Nissan Caroline , Sinkala Moses , Kankasa Chipepo , Mwiya Mwiya , Thea Don , Aldrovandi Grace , Bode Lars
Published: June 2021

We tested the hypothesis that Human Milk Oligosaccharides (HMO) partially account for the inefficiency of HIV transmission through breastfeeding. Using a case‐control design, we measured HMO by HPLC in breast milk samples of 81 HIV‐infected mothers who transmitted HIV via breastfeeding, 86 HIV‐infected mothers who did not transmit and 36 uninfected mothers recruited in Lusaka, Zambia. Only single‐dose nevirapine was used as prophylaxis. Concentration of the individual HMO 3′‐sialyllactose (3′SL) and lacto‐N‐neo‐tetraose was higher in HIV‐infected vs. uninfected mothers. HIV‐infected mothers with concentrations of combined HMO above the median (1.87 g/L) were significantly less likely to transmit via breastfeeding (odds ratio [OR] 0.45[0.21, 0.97], p=0.04) after adjusting for CD4 count and breast milk viral load. Percent HMO that was 3′SL was higher among transmitting vs. non‐transmitting mothers (p=0.005) and correlated with plasma and breast milk viral load and lower CD4 counts. Higher concentrations of HMO and lesser %3′SL were associated with protection against postnatal HIV transmission. Further study of these novel potentially anti‐HIV components of breast milk is warranted.
Understanding facilitators and barriers to pregnant women's participation in a nutrition supplementation program in Bangladesh
Authors: Woo Jisung , Pelto Gretel H , Naved Ruchira T , Frongillo Edward A , Rasmussen Kathleen M
Published: June 2021

An ethnographic study was conducted to explore cultural factors affecting the use of nutritional supplements among pregnant women in rural Bangladesh. In‐depth interviews using a semi‐structured interview guide were conducted with 24 women who had previous experience with a prenatal nutrition supplementation program. Text analysis of transcripts revealed various facilitators and barriers to acquiring and consuming the supplements. Facilitators include support from family, decreased access to food, advice from medical professionals, recognition of the benefits of supplements, and strong individual will. Among the barriers were perceptions of poor appetite, fear of needing a Cesarean delivery caused by a large baby, a gap between anticipated and experienced benefits of supplements, and disapproval by husbands and mothers‐in‐law. Sharing the supplements with others and replacing home diet with the supplement were also barriers to effectiveness. Some barriers had potential to be transformed into facilitators through appropriate actions for modifying women's perceptions. Thus, to enhance pregnant women's participation in a nutrition program, it is essential to obtain participants’ perspectives about supplement use and to address factors affecting their participation, particularly those with the potential to play dual roles.

Grant Funding Source: DNS small grant/Einaudi Center Travel Grant
Household food insecurity reduces the impact of dietary counseling of mothers in Brazil
Authors: Lemos Thaisa S. , Hoffman Daniel J. , Vitolo Marcia Regina
Published: June 2021

The objective of this study was to investigate whether level of food security affects the impact of a dietary counseling among low‐income mothers. Data were collected during a randomized controlled trial in Sao Leopoldo, Brazil. Counseling was given from birth to 12 months of the child. Low food insecure mothers (0–5 points in the Brazilian Scale of Food Insecurity) who received the intervention were more likely to exclusively breastfeed for 4 months (RR = 1.50, p = .008) and breastfeed for 6 months (RR = 1.35, p = .04), and less likely to introduce solid foods before 4 months (RR = .62, p = .04) and soft drinks before 12 months (RR = .68, p = .02) compared to non‐counseled mothers. The intervention had no impact for breastfeeding practices for highly insecure mothers (6–15 points). Counseled mothers were more likely to, in combination, breastfeed for 6 months, introduce complementary feeding after 4 months, and avoid sugar and lipid dense foods for 12 months in both low and highly insecure groups (RR = 1.86, p < .001 and RR = 2.34, p = .01, respectively). In conclusion, food insecurity negatively affected the impact of dietary counseling among low‐income mothers, especially for breastfeeding. However, highly insecure mothers could follow some orientations regarding avoidance of certain foods. Funding was provided by the Brazil National Funding for Research and Capes Foundation of the Brazilian Ministry of Education.
Effect of lactation stage on the content and bioaccessibility of carotenoids in human milk
Authors: Lipkie Tristan Edward , Jouni Zeina E , Sapper Teryn G , Ferruzzi Mario G
Published: June 2021

While the carotenoid composition of human milk has been the subject of several studies, data on the bioavailability of carotenoids from human milk is limited. The purpose of this study was to assess the content and bioaccessibility of carotenoids from human milk collected at different lactation stages. Bioaccessibility and intestinal absorption of milks 1, 4, and 5 months postpartum were assessed using a coupled in vitro digestion/Caco‐2 uptake model. Total carotenoid content of 1‐month, 4‐month, 5‐month postpartum milks were 298±14, 184±4, and 265±3 nM, respectively. Lutein, β‐carotene, and lycopene comprised over 60% of the 12 species of carotenoids identified in each milk sample. Micellerization efficiency (relative bioaccessibility) increased with milk maturation and with increasing polarity of the carotenoid species. During maturation of milk from 1‐month to 5‐months postpartum, micellerization efficiency (mean ± standard error of the mean) of lutein increased from 32±3% to 52±3%, β‐carotene increased from 7±1% to10±1%, and lycopene increased from 2.8±0.4% to 7.2±0.2%. Accumulation of carotenoids by Caco‐2 monolayers was representative of absolute bioaccessible levels following in vitro digestion. These data suggest that carotenoid bioaccessibility from human milk increases during milk maturation as carotenoid levels decrease. Further investigation is required to determine the mechanism(s) by which bioaccessibility is altered. Funding provided by Mead Johnson & Company, LLC.
Impact of meal patterning on carotenoid absorption from vegetables
Authors: Goltz Shellen R. , Sapper Teryn N. , Failla Mark L. , Campbell Wayne W. , Ferruzzi Mario G.
Published: June 2021

The effect of meal patterning on carotenoid absorption is unknown. The aim of this pilot study was to assess the impact of various consumption patterns on the bioavailability of carotenoids from vegetables. On three randomized testing days, subjects consumed equal amounts of fat‐free “chef's salad” ingredients at two meals (hours 0 and 4) along with raw vegetables and 8g canola oil split between the meals in the following dosing patterns: 100 and 0%; 75 and 25%; and 50 and 50%. Blood samples were collected from 0–12h and triacylglycerol rich lipoprotein fractions (TRL) were isolated by ultracentrifugation. Carotenoid contents of TRL fractions were analyzed by HPLC‐PDA. Considering all carotenoids, absorption was greatest when ≥ 75% of vegetables were consumed in the first meal (P=0.06). Absorption of apolar carotenes also followed this trend (α‐carotene: P=0.06; β‐carotene: P=0.05). For more polar xanthophylls, consumption of all vegetables in the first meal promoted greater absorption compared to 75% or less at one time (lutein: P=0.08; zeaxanthin: P=0.05). These data suggest that, within the context of typical meals, carotenoid absorption from raw vegetable salads is greatest when consumed in one setting compared to smaller doses over multiple meals.

Grant Funding Source : USDA‐NRI # 2007‐02313.
The effect of policy change on feeding practices of infants and toddlers in the Special Supplemental Nutrition Program for Women, Infants, and Children in San Marcos, TX
Authors: Reat Amanda M , Crixell Sylvia H , Von Bank Julia A , Friedman BJ
Published: June 2021

In 2009, the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) modified food packages to address rising rates of child obesity and sub‐optimal duration of breastfeeding and offer foods that are more compatible with current dietary guidelines. We collected 24‐hour recalls (using Nutrition Data System for Research) and feeding practices data from 87 caregivers of infants (4–12 mo) and toddlers (1–2 y) in 2009 (pre‐policy change) and from 82 caregivers in 2011 (post‐policy change) to compare feeding practices. In 2011, fewer infants < 6 mo consumed infant cereal (47.1% in 2009 vs. 8% in 2011) and juice (12% in 2009 vs. none in 2011), and more infants > 6 mo consumed baby food meat (none in 2009 vs. 5% in 2011) and baby food fruit (42.4% in 2009 vs. 65% in 2011), reflecting positive changes. However, in 2011, consumption of baby food vegetables was less common among infants > 6 mo (52% in 2009 vs. 43% in 2011) and toddlers (66.7% in 2009 vs. 62% in 2011). Only 62% of toddlers consumed fruit in 2011, compared to 75% of toddlers in 2009. Our results indicate that, in this community, the WIC policy change was helpful but not sufficient to bring feeding practices into compliance with existing guidelines. This research met all Institutional Review Board guidelines and was supported by a Texas State University research enhancement grant.
Barriers and facilitators to the implementation of healthy eating strategies in schools
Authors: Quintanilha Maira , Lieffers Jessica , Farmer Anna , Berry Tanya , Downs Shauna , Mager Diana , Willows Noreen , McCargar Linda
Published: June 2021

In June 2008, the Government of Alberta (Canada) released the Alberta Nutrition Guidelines for Children and Youth aiming to provide schools with a tool to help children and youth make healthy food choices. The purpose of this research was to investigate which factors influenced the early adoption and implementation of the guidelines. A multiple case study design was used. Three urban schools in Alberta were purposefully selected to be the focus of individual case studies. Eighteen key informants among school staff were interviewed; direct observations were also conducted. Content analysis was used to analyze the data. Personal factors (e.g. personal interests) commonly motivated school staff members to support the guidelines. The School Division had a pivotal role in the early adoption of the guidelines, mainly through the work of the superintendent. Changes in the school food environment were often described as healthy eating strategies in response to the guidelines. The work of health champions was identified as a factor that facilitated guideline implementation. In contrast, parents, who did not want to eliminate food choice, were described as a barrier. Overall, many healthy eating strategies were implemented within all three cases due to the guidelines. A health champion is important to overview healthy eating strategies in schools. This research was funded by the Canadian Institutes of Health Research.
State regulation of school food environments is not enough
Authors: Jones Sonya J , Burke Michael P , Frongillo Edward A , Chu Yong , Tompkins Mark , Howlett Michael
Published: June 2021

US States have adopted policies to decrease the availability of competitive foods using regulation, procedures, or resolutions in hopes of preventing obesity. Regulation is often cited as the strongest policy choice, but little is known about which policy instruments will be most effective. We used the Early Childhood Longitudinal Study Kindergarten cohort 2004 and 2007 panels to examine whether children in states that adopted policy instruments by 2004, including regulation, observed subsequent reductions in: 1) school‐level availability, 2) child‐level purchase and consumption of competitive foods and 3) reduction in risk of obesity. We used logistic regression to control for individual and state‐level confounders. We found that no policy instrument, including regulation, was associated with less availability or fewer purchases in school. Furthermore, children in states that passed regulation increased their consumption of sweetened beverages more and had higher prevalence of obesity. States that had the greatest need of policy action because of high obesity rates adopted policies focusing on the school food environment, but the policies did not appear to alter children's consumption or obesity risk. More research is needed into contextual factors that may prevent proper design and implementation of policies.
Vascular Epigenetics by Regulatory RNA: Chance and Necessity [Algorithms] in Adaptation Reactions
Authors: Wissler Josef H
Published: June 2021

OBJECTIVE

From same genotype [twins, clones, polyphenisms], different phenotypes may result from coded genetic [Mendelian] and epigenetic [non‐Mendelian] reactions. Noncoding ncRNAs, the main RNA transcript fraction, were investigated for regulatory functions in epigenetic vascular [angiogenic / arteriogenic] phenotype biology upon extrinsic chemical [metabolic, hypoxic] and physical [mechanosensitive, shear stress] chance factors.

METHODS

Ann. N. Y. Acad. Sci. 1022:163–184, 2004; 1137:316–342, 2008; Biophys. J. 102, 2012.

RESULTS

Upon environmental chance reactions, endothelial cells and macrophages form regulatory RNAs. As for isolated and sequenced angiotropin angiomorphogen RNA, some are modified, edited, redox‐ and metalloregulated functional small hairpin ncRNA [<200n]. Modified bases / nucleosides are e.g. isoguanosine / crotonoside, adenosine‐N1‐oxide of 151Da base families. ncRNAs regulate phenotypic adaptation to environmental needs by complementary interaction with defined conserved homologous helix‐nucleating Mendelian consensus domains shared in epigenetic regulator proteins. Unrelated sequences / conformations and precursors without modifications showed no function.

CONCLUSIONS

The results suggest novel mechanisms and therapeutic targets for metabolically and hemodynamically switched vascular adaptation [angiogenesis / arteriogenesis], like collateral safeguard circulation [form follows function]. Chance and necessity relations generate non‐Mendelian ncRNA diversity as epigenetic codes in interactions with Mendelian‐coded biomolecules and influence how selection impinges on [transient] phenotypes.
A novel kinin‐kallikrein pathway regulates vertebrate mouth formation
Authors: Sindelka Radek , Jacox Laura , Dickinson Amanda , Sive Hazel
Published: June 2021

The mouth, the initial opening between the gut and outside of the embryo, forms from juxtaposed ectoderm and endoderm at the extreme anterior of the embryo. In Xenopus embryos, mouth formation correlates with multiple steps, including cell death, dissolution of the basement membrane, cell layer thinning and intercalation, and cell sheet perforation. From an expression microarray screen we identified three members of the kinin‐kallikrein pathway as highly expressed in the developing mouth region. These are carboxypeptidase‐N, kininogen and neural nitric‐oxide synthase. This pathway acts in adults as a regulator of inflammation and blood pressure, but has not previously been described in embryos. In adults, the pathway converges on production of the signaling molecule nitric oxide (NO). Using antisense oligonucleotides, we show that all three members of this putative embryonic pathway are essential for mouth formation. Consistent with activity of the signaling pathway, all loss of function phenotypes can be rescued by application of exogenous nitric oxide (NO), and by injection of predicted peptide ligands. We further show that endogenous NO is produced in ectodermal tissue and has a role in regulating cell layering during mouth formation. We suggest that the kinin‐kallikrein pathway is active in the embryo and essential for craniofacial development.

Grant Funding Source: AAA
The role of the transcription factor BCL11B in the regulation of growth and asymmetric development of the mouse incisor
Authors: Kyrylkova Kateryna , Kyryachenko Sergiy , Kioussi Chrissa , Leid Mark
Published: June 2021

Development of the mammalian tooth has been intensively studied as a model system for epithelial‐mesenchymal interactions during organogenesis. Furthermore, the mouse incisor regenerates constantly and thus is an excellent model to analyze regulatory pathways that affect dental stem cells. In addition, enamel on the mouse incisor is deposited asymmetrically, which allows the study of differential patterning of the tooth.

The transcription factor BCL11B plays essential roles in the development of immune, central nervous, and cutaneous systems. Bcl11b−/− mice are characterized by poorly developed teeth, however, little is known about the role of BCL11B throughout incisor development.

We investigated the Bcl11b−/− incisor morphology, proliferation, and expression of growth and transcription factors that are crucial for incisor development throughout mouse embryogenesis. We show that BCL11B regulates the expression of several signaling molecules and is essential for epithelial proliferation and asymmetric development of the incisor. In addition, BCL11B contributes to the proper differentiation and localization of enamel‐secreting cells, known as ameloblasts. In conclusion, we demonstrated that BCL11B functions as a critical regulator of proper incisor development, and this study may contribute to the generation of the bioengineered teeth.

Grant Funding Source: DE021879 from NIDCR to ML
Hedgehog responsive mesenchymal clusters direct emergence of intestinal villi
Authors: Gumucio Deborah L , Walton Katherine D. , Kolterud Åsa , Czerwinski Michael J. , Kushwaha Juhi S. , Prakash Ajay , Bell Michael J. , Schnell Santiago
Published: June 2021

Molecular events that underlie emergence and patterning of intestinal villi are unknown. In Gli1LacZ/+ mice, clusters of LacZ positive Hedgehog (Hh) transducing cells form beneath the epithelium prior to villus emergence and remain associated with emerging villi. Clusters initiate anteriorly and dorsally and spread posteriorly and ventrally. These clusters also express Pdgfrα; deletion of Pdgfrα reduces the number of villi but does not prevent villus emergence (Karlsson et al., Development, 2000). Measurement of villus length between E14.5 and E18.5 reveals 8 discrete rounds of villus formation, all of which are associated with mesenchymal clusters. In an explant system, inhibition of Hh signaling prevents cluster formation and abrogates villus emergence, but does not alter Pdgfrα expression. Increasing Hh signaling increases the size of mesenchymal clusters. BrdU pulse chase experiments reveal that clusters form by aggregation of post‐mitotic Hh‐responsive cells rather than by localized proliferation of cells. Thus, mesenchymal clusters that direct the emergence of intestinal villi form in a highly patterned array that presages the regular villus pattern. Hh signaling is required for the aggregation of mesenchymal cells to form signaling clusters that promote villus emergence and dictate the shape of emerging villi. Research Support: NIH DK065850 to DLG
Assessing Formaldehyde Exposure in Your Gross Lab: Occupational Exposure Limits and Best Practices
Authors: Rosen Julia C.
Published: June 2021

Anatomists’ formaldehyde exposures often exceed Occupational Exposure Limits (OELs) set to minimize risks of cancer, allergy and irritation. OELs vary worldwide. The U.S. OSHA regulatory 8‐hour OEL is 0.75 ppm with an Action Level of 0.5 ppm. The 15‐minute Short Term Exposure Limit is 2 ppm. The American Conference of Governmental Industrial Hygienists (ACGIH) recommends a lower Ceiling Limit of 0.3 ppm, which is in use by many countries and is designed to prevent eye and upper respiratory tract irritation. Personal breathing zone air samples are preferred and are typically >2 times higher than area samples. Short‐term sampling captures worst case exposures such as initial dissection of the cranium, abdomen and thoracic cavity. Passive, active and real‐time techniques each have benefit and will be discussed along with the value of using credentialed industrial/occupational hygienists, validated sampling methods and accredited laboratories where available. In the U.S., formaldehyde levels at or above the OSHA Action Level of 0.5 ppm trigger required signage, training, medical monitoring, and personal protective equipment. The challenges of formaldehyde respirator use in gross anatomy labs will be reviewed via a case study. Risk management of sensitive individuals due to pregnancy, asthma or formaldehyde allergy and unregulated individuals such as students and volunteers will also be addressed.
Mechanical tension spatially restricts signals to the leading edge during neutrophil migration
Authors: Weiner Orion David
Published: June 2021

Little is known about how neutrophils and other cells establish a single zone of actin assembly during migration. A widespread assumption is that the leading edge prevents formation of additional fronts by generating long‐range diffusible inhibitors or by sequestering essential polarity components. We use morphological perturbations, cell severing experiments, and computational simulations to show that diffusive‐based mechanisms are not sufficient for long‐range inhibition by the pseudopod. Instead, plasma membrane tension could serve as a long‐range inhibitor in neutrophils. We find that membrane tension doubles during leading edge protrusion, and increasing tension is sufficient for long‐range inhibition of actin assembly and Rac activation. Furthermore, reducing membrane tension results in uniform actin assembly. We suggest that tension, rather than diffusible molecules generated or sequestered at the leading edge, is the dominant source of long‐range inhibition that constrains the spread of the existing front and prevents the formation of secondary fronts.
Genomics and Lipidomics of Macrophage Activation
Authors: Glass Christopher K
Published: June 2021

Inflammation and macrophage foam cells are characteristic features of atherosclerotic lesions and obese adipose tissue, but the mechanisms linking lipid accumulation to inflammation are poorly understood. To investigate this relationship, the LIPID MAPS consortium performed global lipidomic and transcriptomic analysis of peritoneal macrophages in wild type and LDL receptor‐deficient mice fed either a normal diet or a high fat/high cholesterol diet. These genetic and dietary interventions dramatically altered the macrophage lipidome and transcriptome, with synergistic effects observed between the high fat diet and LDL receptor deficiency. Unexpectedly, macrophage foam cells recovered from LDL receptor‐deficient mice exhibited a de‐activated, rather than an activated inflammatory phenotype. Several lines of evidence suggest that desmosterol plays a central role in integrating the homeostatic response of peritoneal macrophages to cholesterol accumulation, acting to inhibit SREBP‐target genes that drive cholesterol biosynthesis and simultaneously promoting LXR‐dependent cholesterol efflux and anti‐inflammatory activities. Desmosterol further orchestrates a metabolic adaptation resulting in suppression of most endogenous fatty acid biosynthesis but enhanced production of oleic acid, the primary fatty acid used for cholesterol esterification, and 9Z‐palmitoleic acid, a putative lipokine that exerts insulin‐sensitizing effects in vivo. Together these findings identify integrative functions of desmosterol in the control of cholesterol and fatty acid homeostasis and inflammatory responses in the macrophage.
Bioorthogonal Chemistries for Glycoprofiling and Beyond
Authors: Bertozzi Carolyn Ruth
Published: June 2021

The glycome is dynamically regulated during development and disease progression. The ability to detect changes in protein glycosylation, in tissue and serum samples as well as in vivo, is of considerable interest for biomarker identification and disease monitoring. This presentation will focus on our work toward profiling glycomic changes using proteomics and in vivo imaging techniques. Bioorthogonal chemistry is central to our approaches, which involve metabolic labeling of glycans with bioorthogonal functional groups followed by chemical tagging with affinity reagents, mass spectrometry tags or imaging probes. Fundamental principles of bioorthogonal reaction development will be discussed, along with applications in cancer biomarker discovery and glycan imaging during embryonic development.
DHA alters EGFR spatiotemporal dynamics to suppress signal transduction
Authors: Turk Harmony Faith , Chapkin Robert S.
Published: June 2021

The epidermal growth factor receptor (EGFR), which regulates cell growth and survival, is integral in colon tumorigenesis. Lipid rafts play a role in controlling EGFR signaling, and docosahexaenoic acid (DHA) is known to perturb lipid rafts. Here, we investigated the mechanistic link between EGFR function and DHA. DHA treatment of immortalized colonocytes and C57BL6 mouse colonic mucosa increased EGFR phosphorylation but paradoxically suppressed downstream activation of STAT3 and ERK1/2. DHA also suppressed cell proliferation in an EGFR‐dependent manner. The EGFR‐Ras‐ERK1/2 signaling cascade was assessed to identify the locus of the DHA‐induced disruption of signal transduction. Recruitment of Grb2 to EGFR, assessed using total internal reflective fluorescence (TIRF) microscopy, was increased by DHA treatment, whereas Ras GTP binding, a lipid raft‐dependent process, was suppressed by DHA treatment. Colocalization and membrane subfractionation experiments demonstrated that DHA reduced the localization of EGFR to lipid rafts. DHA further antagonized EGFR signaling capacity by increasing the rates of EGFR internalization and degradation. From these results, we conclude that DHA‐induced dissociation of EGFR from lipid rafts culminates in the suppression of EGFR downstream signal transduction, which has implications for the molecular basis of colon cancer prevention by DHA.

Grant Funding Source : NIH CA59034
Bovine lactoferrin and bovine lactoferricin are internalized by colon cancer cells and exhibit elevated apoptosis
Authors: Jiang Rulan , Lonnerdal Bo
Published: June 2021

Lactoferrin (Lf) is an iron‐binding glycoprotein and is present at high concentrations in milk from several species. Bovine lactoferricin (bLfcin) is a peptide fragment produced by acid‐pepsin hydrolysis of bovine lactoferrin (bLf). BLfcin consists of amino acid residues 17–42 proximal to the N‐terminal of bLf and a cysteine–cysteine disulfide bond between residues 19 and 36 creating a cyclic form. Both bLf and BLfcin have been shown to have anti‐tumor activities. Colorectal cancer is the 2nd most common cause of cancer deaths in developed countries. Therefore, we hypothesized that both bLf and bLfcin are internalized by colon cancer cells (HT‐29) and stimulate apoptosis of these cells. Confocal microscopy showed that bLfcin in linear and cyclic forms and bLf were internalized by HT‐29 cells. ApoTox‐Glo Triplex Assay (Promega) results show that bLfcin and bLf significantly stimulated apoptosis of colon cancer cells in a concentration‐dependent pattern and maximal effects were obtained at 12‐h of treatment. No significant differences were found between the two forms of bLfcin, but the effect on apoptosis triggered by bLfcin was stronger than that by bLf. In summary, both bLfcin and bLf are internalized by colon cancer cells and stimulate apoptosis of these cells, suggesting potential clinical applications for bLf and bLfcin in colon cancer.
Intergenerational exergaming physical activity program increases flexibility and strength in older adults
Authors: Strand Kara Anne , Francis Sarah L. , Margrett Jennifer A. , Franke Warren D. , Peterson Marc J.
Published: June 2021

Exergaming is an innovative strategy to improve community‐residing older adults’ fitness. This crossover design study examined the impact an intergenerational 8‐week exergaming program for community‐residing older adults had on fitness levels. The program met twice weekly (60 minutes of Wii® EA Active total). It combined aerobic and resistance activity with increased intensity and duration. Data were analyzed using descriptive statistics and paired sample t‐tests. Missing data are not included. Forty‐six older adults completed the program (67.6% completion rate). Senior fit tests (chair stand, back scratch, and handgrip [using dynamometer]) were completed at Weeks 1 and 8. Improvement was seen in the number of chair stands (p=0.002), average back scratch flexibility (p=0.029), and left hand grip strength (p=0.041) from pre‐ to post‐program. These results suggest an intergenerational exergaming program is an effective strategy in improving flexibility and strength in community‐residing older adults.

Funded by: The Rural Health and Safety Education Competitive Program of the USDA National Institute of Food and Agriculture, grant number 2010‐03643.
Total forearm bone mineral density measured by a portable peripheral x‐ray agrees with dual‐energy x‐ray absorptiometry
Authors: Hazell Tom J , Vanstone Catherine A , Pham Thu Trang , Jean-Philippe Sonia , Rodd Celia J , Weiler Hope A
Published: June 2021

Measurement of bone mineral density (BMD) using dual‐energy x‐ray absorptiometry (DXA) typically requires a research facility or specially designed mobile facilities. However, neither is suitable for reaching remote regions without road or sea access. Thus, the potential to use a portable peripheral x‐ray (PIXI) scanner requires validation. This study aimed to determine the agreement between forearm BMD measured using DXA vs PIXI. Fifty‐seven pre‐school children (29 boys, 28 girls; 4.2±1.0y) had the distal 1/3 forearm of their non‐dominant arm scanned using PIXI (Lunar GE Medical) at their daycare and DXA (Hologic 4500A Discovery Series) at our research clinic. One‐way ANOVA, correlation analysis, and Bland‐Altman plots were performed to examine agreement between measurements (total forearm, radius, ulna), significance was set at P<0.05. Forearm BMD, correlation, and ANOVA results for PIXI and DXA are presented in Table 1. The PIXI and total forearm BMD were also in good agreement in a Bland‐Altman plot (bias=0.003; 95% CI=−0.041 to 0.046). These results demonstrate that portable PIXI measures of total forearm BMD agree well with DXA. Supported by Dairy Farmers of Canada.
The association between food patterns and adiposity in Canadian children
Authors: Wang JiaWei , Shang Lei , Gray-Donald Katherine , Lambert Maire , O'Loughlin Jennifer , Tremblay Angelo
Published: June 2021

To describe food patterns associated with obesity, children (n=561) with at least one obese parent, were recruited into the Quebec Adiposity and Lifestyle Investigation in Youth (QUALITY) cohort and studied cross‐sectionally at baseline. Measures of adiposity (BMI, waist circumference, fat mass), screen time, physical activity (accelerometer over 7 d), and diet (three 24‐h food recalls) were collected. Factor analysis was used to identify food patterns. Three food patterns were retained: fast food (sugar‐sweetened beverages, fried potatoes, fried chicken, hamburgers/hot dogs/pizza, salty snacks), traditional food (red meats, poultry, fish, vegetables, etc) and healthy food (whole grains, legumes/nuts/seeds, salads). Higher scores on the fast food pattern were associated with overweight/obesity (BMI≥85th percentile), waist circumference, fat mass percentage after adjustment for age, sex, physical activity, screen time, sleep time, family income, mother's obesity and energy intake (P<0.05). The results provide further evidence of a link between fast food intake and obesity in children.

Grant Funding Source : Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada and Fonds de la recherche en santé du Québec
Consumption of Helianthus tuberosus Linne and chungkookjang have additive anti‐diabetic effects in diabetic rats
Authors: Park Sunmin , Kwon Dae Young , Yang Hye Jeong , Kim Min Jung , Daily Jim
Published: June 2021

Helianthus tuberosus Linne (HTL) rich in fructoligosaccarides and chungkookjang (CKJ; fermented soybeans) containing isoflavonoid aglycones and small peptides is known to modulate glucose metabolism. However, the action mechanism and their additive effects were not determined. We investigated whether the consumption of HTL and CKJ alters glucose homeostasis in type 2 diabetic rats. The 90% pancreatectomized (Px) diabetic rats were provided with high fat diets containing 10% HTL, CKJ or HTL+CKJ for 8 weeks. None of the Px rat groups experienced changes in body weight but HTL reduced visceral fat without modulating caloric intake, compared to the control. Both HTL and CKJ improved glucose tolerance compared to the control and HTL+CKJ resulted in additive effects. HTL alleviated hepatic insulin resistance better than CKJ during the euglycemic hyperinsulinemic clamp. The improvement in hepatic insulin sensitivity by HTL and CKJ was explained by the potentiated insulin signaling (pyIRS2→pAkt) and pAMPK→pACC and decreased PEPCK expression. HTL reduced hepatic glucose output. CKJ potentiated glucose‐stimulated insulin secretion better than HTL during hyperglycemic clamp. HTL decreased β‐cell apoptosis, but not proliferation, compared to the control and HTL did not increase β‐cell mass as much as CKJ. In conclusion, the combination of HTL and CKJ additively improves glucose homeostasis in diabetic rats.
Social influences on sugar consumption during pregnancy
Authors: Graham Jocelyn , Forbes Laura E , Mayan Maria , McCargar Linda , Bell Rhonda C ,   The Sweet Moms Team
Published: June 2021

Studies of dietary intake during pregnancy have shown that many women increase their sugar intake during this time, which may contribute to poor diet quality and excess weight gain. The purpose of this research is to investigate physiological, social, and environmental factors that influence sugar intake during pregnancy.

Guided by the methodology of focused ethnography, a series of semi‐structured interviews (n=8) have been conducted with pregnant women of varying sugar intakes. Transcripts were analyzed using qualitative content analysis to inductively derive knowledge about sugar intake.

Preliminary findings from this study that have reached saturation include three social influences on sugar intake behaviours. Women conveyed an attitude that the state of pregnancy is a license to indulge in foods that are usually limited or avoided. Fathers could have either a positive or negative effect on the sugar intakes of women depending on their own dietary habits and views. Furthermore, social expectations of nutrition in pregnancy affected people's behaviours towards pregnant women and influenced eating behaviours during pregnancy.

Strategies to facilitate healthier diets during pregnancy may include altering women's beliefs and attitude towards food and weight gain, including the father in nutritional counseling, and public health campaigns to increase knowledge of nutrition during pregnancy.
Grape polyphenols improve blood pressure and vascular function in men with metabolic syndrome
Authors: Barona Jacqueline , Volek Jeff S , Fernandez Maria Luz
Published: June 2021

Men (n=24, 30–70y) with metabolic syndrome (MetS) were randomly allocated to consume either a freeze‐dried grape polyphenol powder (GRAPE) or a placebo for 30 days in a double blind manner. After a 3‐wk washout, they were allocated to the alternate treatment. Participants maintained their usual diet and physical activity during the study and abstained from consuming polyphenol‐rich foods. MetS parameters and markers of vascular endothelial function [flow‐mediated vasodilation (FMD) of the brachial artery, plasma total nitric oxide (NOx), plasma soluble intercellular adhesive molecule‐1 (sICAM‐1) and vascular cell adhesive molecule‐1 (sVCAM‐1) were measured]. There was a significant (p= 0.002) decrease in systolic blood pressure (BP), greater FMD response (p= 0.000), and reductions in circulating sICAM‐1 concentrations (p= 0.017) during the GRAPE compared to the placebo period. In addition changes in sICAM‐1 concentrations between periods were negatively correlated with absolute FDM changes (r = −0.479, P < 0.025). Although NOx concentrations were not different between periods, changes in systolic BP were negatively correlated (r = −0.437, p < 0.05) with changes in NOx concentrations indicating the vasodilating properties of NOx. These results suggest that GRAPE polyphenols may potentiate vasorelaxation and reduce circulating adhesive molecules, as well as reduce BP and improve vascular dysfunction

Grant Funding Source : California Table Grape Commission
Whole apple but not apple pectin affects cardiac pathology and the oxidative stress/antioxidant transcriptome in obese rats
Authors: Seymour E Mitchell , Brickner Paula R , Bosak Kristen N , Kondoleon Michael G , Bolling Steven F
Published: June 2021

Apples provide both pectin fiber and phytochemicals that may confer cardiac benefits. However, their comparative effects on hypertension and cardiac function are unknown. In the obesity‐prone Zucker Fatty rat, we compared three diets: freeze‐dried whole apple powder (APP, 10% w:w), apple pectin (PEC), or control (CON). Diets were matched for macronutrients and calories, and animals were provided equivalent food per day. Body weight, fat mass and lean mass were not significantly different among groups. However, APP caused progressive reductions in serial systolic blood pressure, while PEC only caused transient and non‐significant reductions. After 120 days, APP but not PEC reduced cardiac hypertrophy, improved diastolic function, increased cardiac output, and reduced fibrosis. APP also reduced plasma oxidative stress marker malonyldialdehyde. APP but not PEC affected the cardiac transcriptome related to pro‐inflammatory NFκB activation and to antioxidant defense. Both APP and PEC reduced cardiometabolic risk factors like serum triglycerides, total cholesterol and fasting glucose but increased fecal cholesterol and bile acid content. Results suggest that diet‐altered lipid and glucose handling did not reduce cardiac pathology. In addition, reduced tissue oxidative stress by whole apple may be critical to cardiac‐specific effects; apple‐derived phytochemicals may mediate these benefits.
Reduction in high‐calorie food reward after a lifestyle intervention in obese endometrial cancer survivors
Authors: Nock Nora L , Dimitropoulos Anastasia , Frasure Heidi , von Gruenigen Vivian
Published: June 2021

Obesity is associated with an increased risk of endometrial cancer (EC) and, EC patients have the highest risk of death among all obesity‐associated cancers. Yet, only two lifestyle interventions targeting EC survivors have been completed. EC patients lost weight in these trials but food disinhibition, as determined by the Three‐Factor Eating Questionnaire, decreased, suggesting an increase in emotional eating and, possibly, food reward. We evaluated food behavior using a visual functional magnetic resonance imaging (fMRI) task involving paired stimulus presentation of high‐calorie, low‐calorie and non‐food images in 11 obese, Stage I/II EC patients enrolled in Survivors in Uterine Cancer Empowered by Exercise and a Healthy Diet (SUCCEED), a lifestyle intervention aimed at improving nutritional and exercise behaviors in 16 group sessions over 6 months using social cognitive theory. At 6 months post‐intervention compared to baseline, we observed a decrease in activation in brain regions involved in food reward and motivation (posterior cingulate, globus pallidus, thalamus; cluster corrected p<0.005) in response to high‐calorie vs. non‐food contrasts in the fed state in the Tx group (n=8). These changes were not found in the UC group (n=3). To our knowledge, this is the first study to demonstrate that a behavioral lifestyle intervention helps to reduce high‐calorie food reward in obese EC survivors.