bluuebunny/crossref_metadata_2025 huggingface dataset:
The challenge of teaching Anatomy in a organ‐based curriculum:mistakes made and lessons learned
Authors: Adamas‐Rappaport William Joaquin , Czuzak Maria Helen , Alvarado Jared , Darnell Diana
Published: June 2021

In 2006 the University of Arizona College of Medicine underwent a curriculum change from the traditional system based format to an organ‐ system based curriculum. Gross Anatomy went from its own separate course to being part of each block through the first two years of the basic sciences. Overall focus on Anatomy was diminished.

Challenges encountered.

‐Shortened time for dissections.

‐Anatomy accounting for a minimal percentage of total grade.

‐ Dissection carried on throughout the whole 1st year.

‐When to use prosections instead of student dissections.

Innovations

‐ Anatomy elective during the 4th year.

‐ Fresh cadaver based surgeries with emphasis on anatomy for students going into surgical specialties offered in the 4th year.

‐ Fresh cadaver based instruction for all 3rd year students rotating on the surgery clerkship.

‐Fresh cadaver based ultrasound instruction introduced on the surgery clerkship.

‐ Anatomy couse offered to pre‐medical students with medical students acting as instructors.

Conclusions

The change in curriculum to an organ‐based format posed a challenge as to how best to teach Anatomy. New and innovative methods must be introduced to insure graduating medical students have the fundamental knowlege of Anatomy especially focused on the clinical path they will pursue.
Caffeine, alcohol and overall nutrient adequacy are associated with longitudinal cognitive performance among US adults
Authors: Beydoun May A , Gamaldo Alyssa , Beydoun Hind A. , Tanaka Toshiko , Tucker Katherine L. , Talegawkar Sameera , Ferrucci Luigi , Zonderman Alan B
Published: June 2021

The relationships of caffeine, alcohol and nutrient adequacy with cognitive performance were examined using data from a prospective cohort study, the Baltimore Longitudinal Study of Aging (n=628–1,305;~2 visits/person). Outcomes included ten cognitive test scores, spanning various domains. Caffeine and alcohol intakes and a nutrient adequacy score(NAS) were estimated from 7‐d food diaries. Multiple linear mixed models (Time=years since baseline assessment), indicated that caffeine was associated with better baseline global cognition, overall and for subjects with baseline age(Agebase)≥70y. Caffeine was also related to better baseline performance on visual memory overall, but with a faster decline on that domain over time. Higher NAS was linked to slower decline on verbal memory, immediate recall(overall,men, Agebase<70y) and attention(women, Agebase<70y), better baseline performance on immediate and delayed recall(Agebase≥70y), but with faster decline on global cognition and visual memory(Agebase<70y). For Agebase<70y, alcohol was linked to faster decline on letter fluency and global cognition. Conversely, for Agebase≥70y, alcohol was related to better baseline attention and working memory. Models with Time=Age centered at 50y were consistent. In sum, mixed patterns of association indicate modification by baseline age and sex, requiring more longitudinal studies.
Impact of computer‐mediated nutrition education interventions in adolescents: a systematic review
Authors: Ajie Whitney , Chapman‐Novakofski Karen
Published: June 2021

Objectives were to assess web/computer‐based interventions’ effectiveness for adolescents (11–18y); identify which intervention element(s) made the most impact on nutrition‐related variables; and ascertain recommendations for research/practice. Online databases/journal archives were systematically searched using key words; related articles’ bibliographies manually searched. One author examined abstracts for review inclusion; both authors conducted quality assessments using USDA's National Evidence Library's guidelines for Research Design/Implementation. Initial article retrieval (n=37488) was reduced to 14 using inclusion/exclusion criteria. Randomized controlled trials (RCTs) for preventing weight gain (n=2), weight loss (n=2) had NS results; RCTs (n=6), Non‐RCTs (n=4) for healthy eating (HE) included significant and NS results for HE components. Optimal intervention duration couldn't be concluded. Studies lacking behavior theory (n=6) had NS (n=3), significant (n=3) results; those with behavior theory (n=8) had mostly significant results (n=7), some gender‐specific (n= 3). Neither setting nor parental involvement influenced outcomes. Research needs include studies with stronger design (randomization, power analyses, treatment fidelity, mediating variable measurements, long‐term evaluation) in order to develop computer‐based nutrition education best practices.

Grant Funding Source: Kraft Fellowship
Pharmacokinetics of 13C‐Lycopene in Healthy Adults
Authors: Moran Nancy E , Cichon Morgan J. , Riedl Kenneth M. , Grainger Elizabeth M. , Schwartz Steven J. , Erdman John W. , Clinton Steven K.
Published: June 2021

Higher plasma lycopene (LYC) concentrations are associated with lower risk of several cancers. (All‐E)‐LYC is the predominant geometrical isomer in tomatoes, yet most plasma and tissue LYC isomers are Z, suggesting greater bioavailability of Z and/or endogenous isomerization of E to Z. To study human LYC pharmacokinetics and isomerization, ~10 mg of 13C‐LYC isolated from tomato cell cultures was consumed with breakfastby 6 healthy adults. The dose was 85% (all‐E)‐LYC, and ~30% uniformly labeled. Plasma was collected at 1–10, 24, 72, and 672 hrs post‐dosing. Native and 13C‐LYC was analyzed by HPLC‐PDA, and LC‐MS (QToF), respectively. No adverse effects of 13C‐LYC were observed. 13C‐LYC Cmax= 0.13±0.03 μM which occurred at 32±8 hr, T1/2 = 6.5 ± 0.3 d, and area‐under‐the‐curve (AUC0–672) = 36.9±7 μM*h. Plasma 13C‐all‐E‐LYC Cmax =0.10 ±0.02 μM at 29±9 h post‐dosing, T1/2 = 5.5±0.3 d, and it constituted 67% of total 13C‐LYC AUC. Total 13C‐Z‐LYC isomers Cmax =0.03 ± 0.005 μM at 56±10 hr post‐dosing with a subsequent T1/2 = 9.3±0.6 days, and constituted 32% of the total 13C‐LYC AUC. Initial plasma 13C‐LYC was 73–87% all‐E, but by 672 hr, had decreased to 46%. The later Z isomer Cmax and longer T1/2 relative to all‐E suggests that endogenous conversion is a source of circulating Z‐LYC isomers. Understanding LYC pharmacokinetics assists in designing anti‐cancer dietary interventions.

Grant Funding Source: NCCAM R21AT005166, Pelotonia, OSUCCC NPASR
Developmental origins of novel gut morphology in frogs
Authors: Nascone‐Yoder Nanette , Bloom Stephanie , Ledon‐Rettig Cristina , Infante Carlos , Hanken James
Published: June 2021

Phenotypic variation is a prerequisite for evolution by natural selection, yet the processes that give rise to the novel morphologies upon which selection acts are poorly understood. We employed a chemical genetic screen to identify developmental changes capable of generating morphological variation as observed among extant species. Specifically, we assayed for small molecules capable of transforming the ancestral larval foregut of the herbivorous Xenopus laevis to resemble the derived foregut of the carnivorous Lepidobatrachus laevis. Appropriately, the small molecules that demonstrate this capacity modulate morphogenetic pathways involved in gut development, including retinoic acid (RA) signaling. Identical manipulations in a species more closely related to Lepidobatrachus, Ceratophrys cranwelli, yielded even more similar transformations, corroborating the relevance of RA signaling variation in interspecific morphological change. Finally, we were able to recover the ancestral gut phenotype in Lepidobatrachus by performing a reverse chemical manipulation to upregulate RA signaling, providing strong evidence that modifications to this specific pathway promoted the emergence of a lineage‐specific phenotypic novelty. Small molecule screening may be valuable for identifying developmental mechanisms that underlie ecologically and evolutionarily relevant phenotypic variation.
Hyper‐O‐GlcNAcation links cancer metabolism to oncogenic signaling.
Authors: Vosseller Keith , Ma Zhiyuan
Published: June 2021

Cancer cell metabolic reprogramming of energy production to the relatively inefficient glycolytic pathway (Warburg effect) necessitates increased glucose uptake. Glucose flux through the hexosamine biosynthetic pathway (HBP) leads to production of UDP‐N‐acetylglucosamine (UDP‐GlcNAc), used in enzymatic post‐translational modification of cytosolic/nuclear proteins by O‐linked β‐N‐acetylglucosamine (O‐GlcNAc). We observe increased HBP flux, elevated levels of the enzyme that adds O‐GlcNAc (OGT), and hyper‐O‐GlcNAcation in human cancers. Genetic and pharmacological reduction of cancer hyper‐O‐GlcNAcation inhibits transformed phenotypes. Silencing OGT to reduce O‐GlcNAc had no effect on non‐transformed pancreatic epithelial cell growth, but inhibited pancreatic ductal adenocarcinoma (PDAC) cell proliferation, anchorage‐independent growth, orthotopic tumor growth, and triggered apoptosis. Constitutive NF‐κB activity is anti‐apoptotic in many cancers. Reducing hyper‐O‐GlcNAcation decreased PDAC NF‐κB activation, while pharmacologically mimicking PDAC hyper‐O‐GlcNAcation activated NF‐κB. Specific mutation of two NF‐κB p65 subunit O‐GlcNAc sites (T322 and T352) to alanines reduced p65 O‐GlcNAcation and attenuated PDAC cell anchorage‐independent growth. Our data indicates that PDAC hyper‐O‐GlcNAcation is anti‐apoptotic and contributes to NF‐κB oncogenic activation.
CRISPR/Cas, the RNA‐based adaptive immune system of prokaryotes
Authors: Marraffini Luciano A
Published: June 2021

Clustered, regularly interspaced, short palindromic repeat (CRISPR) loci and their associated proteins (Cas) protect bacteria and archaea from bacteriophages, viruses that infect these organisms. Immunity requires a sequence match between the invasive DNA and phage‐derived sequences that lie between CRISPR repeats, also known as “spacers”. CRISPR loci are transcribed into long precursors that are processed into small CRISPR RNAs (crRNAs) by Cas endoribonucleases. Target recognition occurs through base‐pair interactions between the crRNA spacer sequence and the invading nucleic acid and result in the cleavage of the bacteriophage genome. Essential for crRNA processing and targeting are Cas ribonucleoprotein complexes. We will discuss recent advances in the molecular mechanisms of CRISPR targeting and their importance for the evolution of bacteria and their viruses.
Development of a manipulative for renal physiology teaching
Authors: Giffen Zane , Carvalho Helena
Published: June 2021

Human physiology is a difficult subject to teach because it requires the integration of knowledge and use of reasoning to understand complex concepts. Accordingly, it has been shown that learning is improved when instruction is interactive and engaging. The goal of this project was to develop a hands‐on manipulative to aid first year medical students in their understanding of renal physiology. A magnetic manipulative model of the nephron and its major cell types was constructed using large magnetic boards to represent components of the nephron, magnets to represent transporters, and plastic pieces to represent select small molecules and electrolytes. These pieces can be moved between the tubular lumen, epithelial cells of the tubule, and interstitium in different areas of the nephron to illustrate secretion and reabsorption in the tubule and the dynamic process of urine formation. In summary, an interactive model was developed from inexpensive materials that allow students to reinforce their understanding of renal physiology through active participation.

Support from Center for Instructional Development and Educational Research (CIDER) at Virginia Tech
Pathogenic E. coli Cause Global Decreases in Ubiquitylated Host Cell Proteins
Authors: Lin Ann E. , Guttman Julian A
Published: June 2021

Enteropathogenic E. coli (EPEC) infections cause severe infantile diarrhea, leading to high mortality in developing countries. These pathogens extensively alter normal host cell functions while remaining extracellular. Ubiquitylation is a widespread post‐translational regulatory system that governs a wide range of cellular events. This process relies on a heierarchical relay system, comprised of E1, E2 and E3 enzymes. Effects of EPEC on the host ubiquitin‐conjugation process have remained elusive. Thus, we sought to test the hypothesis that EPEC alter normal ubiquitylation signaling pathways during their infections. To test this, we infected epithelial cells with EPEC and monitored ubiquitylated protein levels by immunoblotting. We found that the presence of a large plasmid within EPEC called the E. coli adherence factor (EAF) caused a significant decrease in the overall levels of ubiquitylated host proteins. This occurred with a concomitant loss of host E1 activating enzymes, which are essential for initiating the ubiquitylation cascade. We conclude that EPEC exploits E1 enzymes to influence global protein regulatory cascades that are crucial for normal cellular functions. This novel strategy highlights that pathogens can exploit key targets to influence overall protein regulatory systems that are needed for normal cellular functions and disease progression.

Grant Funding Source: CIHR
Three decades of recurrent manic episodes modulated by nineteen years of lithium therapy
Authors: Canolty Nancy L. , Jennings Marcus R.
Published: June 2021

Investigations of mania without depression are limited. This study is based on a 34‐year record by one of the authors (nlc) who first experienced a manic episode in 1978 at the age of 36. Lithium therapy was begun in the midst of an episode seven years later, continued for 19 years, then discontinued. Overall, without depression, there were 102 manic episodes with a mean duration of 18 days per episode. Episodes before (Period I), during (Period II), and after (Period III) lithium therapy were compared. In Period I (7 yrs) there were 12.7 episodes with a mean frequency of 1.8 episodes per year and a mean duration of 17 days per episode. In Period II (19 yrs) there were 63.3 episodes with a mean frequency of 3.4 episodes per year and a mean duration of 14 days per episode. In Period III (9 yrs) there were 26.0 episodes with a mean frequency of 3.0 episodes per year and a mean duration of 28 days per episode. Overall, 85% of the days were episode‐free during the 34‐year period of recurrent manic episodes. In Periods I, II and III, 92%, 87% and 77%, respectively, of the days were episode‐free. This demonstrates that episode‐free days were not increased during or after 19 years of lithium therapy.
In Response to Damage Activated Microglia Enhance Neuronal Differentiation and Survival
Authors: Chen Jing , Shibata Annemarie
Published: June 2021

Contribution of microglia to neurogenesis under different pathological conditions is unclear. Both pro and anti‐neurogenic effects have been reported, reflecting the complexity and heterogeneity of microglial activation and effects. In this study, we have developed an in vitro model system designed to co‐culture microglia in transwells suspended above mechanically damaged or undamaged primary neuronal cultures. Immunocytochemistry, Western blot, and RT‐PCR analysis of damaged neurons co‐cultured with microglia at specific time points indicates developmentally regulated expression of nestin, α‐internexin, GFAP, β‐tubulin III, and NeuN when compared to damaged neurons that were not co‐cultured with microglia. Analysis of co‐cultures also shows increased activation of the PI3K/AKT and MAPK signaling pathways suggesting microglial secretion may utilize these pathways to promote neuronal differentiation and survival. Further we are examining neurotrophic microglial induced changes in neuronal epigenetics through the targeting of histone modifications and transcription factors such as REST and co‐REST. Our data suggests that microglia may possess modifiable properties to become potential targets for neuroprotective therapies. Research is funded by NIH grant number P20 RR016469 from the INBRE Program of the National Center for Research Resources.
Corepressors LCoR and KAP1 form a complex with the transcription factor ZBRK1 to silence FGF2 gene expression and maintain breast cancer cell viability
Authors: Calderon Mario Ramiro , Verway Mark , Mader Sylvie , White John H
Published: June 2021

Through the use of a yeast two‐hybrid screen, we have a found a novel interaction between the C‐terminal domain of the transcriptional coregulator ligand‐dependent corepressor (LCoR) and the transcriptional corepressor Kruppel‐associated protein‐1 (KAP‐1). These transcriptional regulators associate with the transcription factor ZBRK1 and repress the expression of the Fibroblast Growth Factor 2 (FGF2) and Growth Arrest and DNA‐Damage‐inducible alpha (GADD45A) genes in breast cancer cell lines. Remarkably, ablation of ZBRK1, KAP‐1, or LCoR expression led to apoptotic death of specific breast cancer cells. This loss of viability could be partly rescued by simultaneous knockdown of FGF2, which abrogated the elevated FGF2 production in ZBRK1‐, KAP‐1, or LCoR‐deficient cells. Studies show that more malignant phenotypes in breast cancer are associated with loss of FGF2 expression, although the mechanism of this loss is poorly understood. We propose that ZBRK1, KAP‐1, and LCoR form a transcriptional complex that silences expression of genes, in particular FGF2, which enhances specific breast cancer cell viability. Research funded by the Canadian Institutes of Health Research (CIHR).
The role of Zinc Binding Protein‐89 (ZBP‐89) in basal and IL‐1 induced expression of matrix metalloproteinase‐3 (MMP3)
Authors: Scianni Stephanie N , Gorski Grzegorz , Foster Sara , Borghaei Ruth
Published: June 2021

MMP‐3 plays an important role in normal and pathological tissue remodeling, and its expression of is regulated by a variety of cytokines, growth factors, and hormones, mainly at the level of transcription. Transcription factor ZBP‐89 has been shown to interact with a polymorphic promoter sequence and activate transcription of the MMP‐3 gene when over‐expressed. To examine the role of ZBP‐89 in basal and IL‐1‐induced expression of MMP3 we knocked down ZBP‐89 in the MG63 cell line. MMP‐3 mRNA expression was measured by real‐time PCR and compared with expression in a negative control cell line. The basal expression of MMP‐3 was significantly lower in the knockdown cell line when compared to negative control. This is consistent with ZBP‐89 as an activator of basal expression. IL‐1 fold induction was significantly higher at 6 hours in the knockdown cell line, which is consistent with a role of ZBP‐89 as a repressor of IL‐1 induced expression of MMP‐3.
Targeting melanocortin‐4 receptor (MC4R) agonists to the endoplasmic reticulum (ER) as a potential approach to obesity therapy
Authors: Molden Brent Matthew , Granell Susana , Baldini Giulia
Published: June 2021

Melanocortin‐4 receptor (MC4R) is a G‐protein coupled receptor (GPCR) expressed in the hypothalamus where it controls food intake. Agonist binding, including that of natural agonist alphamelanocyte stimulating hormone (α‐MSH), stimulates receptor activity and suppresses appetite. Previous studies found that MC4R undergoes agonist‐mediated desensitization, and treatment with extracellular MC4R agonists led to tachyphylaxis in mice. Here, we use Neuro2a cells expressing HA‐MC4R‐GFP to study receptor localization and function by immunofluorescence microscopy and ELISA. We find that ER‐targeted α‐MSH binds to MC4R in the ER, traffics to the cell surface with the receptor, and induces constant receptor activity. After internalization, the receptor escapes routing to the lysosomes and desensitization, consequently the signal generated maintains maximal amplitude. Most naturally occurring MC4R mutations in humans and mice lead to MC4R retention in the ER and cause obesity. Expression of ER‐targeted α‐MSH doubles traffic of obesity‐linked MC4R I316S to the cell surface. We conclude that targeting of α‐MSH to the ER is a novel approach to promote MC4R signaling without desensitization and to rescue traffic of obesity‐linked MC4R variants to the cell surface.
Pectinase hyperproduction in Fungi Isolates
Authors: Okafor Uzoma A , Ebuehi Albert O , Okochi Veronica I , Adekunle Adedotun , Magbagbeola Olubunmi a
Published: June 2021

Improving the yield of enzyme production via microfungi strain improvement using UV mutation has become a priority in most enzymes generating countries, for economic and ecological reasons.

In view of these reasons, Hyper‐production of pectinase by these strains using UV as mutagen and 2dg as selectant was studied. The mutant strains were compared based on the enzyme production, catabolite repression and the genetic variability between wild and mutant strain was investigated using Random Amplified Polymorphic DNA (RAPD) primers.

Three Aspergillus niger 2dg UV mutants and five P.chrysogenum 2dg UV mutants were isolated post exposure of the strains to UV irradiation. 2 dg UV M2 mutant of Aspergillus niger was selected as best mutant with an enzyme activities of 465% and 230% in SSF and SmF respectively. P.chrysogenum 2DG‐UV W1, gave a percentage enzyme activity of 218% in solid state fermentation, and 2DG‐UV W2 gave a better pectinase yield (135%) in SSF. The glucose showed no repression (CR) on pectinase production of both the 2dg UV M2 and 2dg UV W1. However, sucrose repressed pectinase production in P.chrysogenum. The results of RAPD‐PCR showed a considerable genetic variation between the wild and mutant strains of both fungi strains

This work shows that the natural process of biodegradation and UV mutagenesis could be harnessed for the bioproduction of pectinase an important enzyme in major fermentation industries.
Fluorescent nanoparticles based on fluorescein
Authors: Araujo Ana Paula Vieira , Gomes Anderson J
Published: June 2021

This study aimed to demonstrate the characterization of the fluorescent compound fluorescein when encapsulated in Tetraethyl orthosilicate nanoparticles (TEOS). In this study, fluorescein was incorporated in TEOS nanoparticles using the sol‐gel process and these particles were evaluated in relation to size using dynamic light scattering (DLS), zeta potential, drug encapsulation efficiency, and external morphology using scanning electron (SEM) and spectroscopic properties. The fluorescein was loaded into TEOS nanoparticles, and the better entrapment efficiency was 75%. SEM and DLS revealed that the particles are spherical in shape, being the smallest size approximately 180 nm, and show low tendency to aggregate, confirmed by zeta potential ranging around of −39 mV and −50 mV. Those results suggest that TEOS nanoparticles can be used asociated to antitumoral drugs and locate tumor cells using fluorescence imaging assays. Financial support: CNPq, CAPES, FAPDF, FINATEC, DPP‐UnB
Developing a robust POGIL model to connect basic biochemistry to the physiological changes during starvation
Authors: Dean Diane , Anderson Ellen
Published: June 2021

The inquiry approach to science education has been recommended by the National Science Foundation (NSF) and the American Association for the Advancement of Science (AAAS) for several decades. Process‐oriented Guided‐inquiry Learning (POGIL) is a pedagogy that was developed to teach introductory chemistry as a response to the recognized need by NSF and AAAS. It was expanded to biochemistry for major courses in the last 5 years. Nursing and allied health students constitute a population that has not benefitted from this pedagogy revolution. Training in all the medical professions includes foundational course work in biochemistry. Making that coursework relevant to the student through inquiry exercises is critical for retention of the material. One of the objectives taught through this exercise is to describe the changes in amino acid metabolism during early starvation and fasting. The exercise uses several robust models to help the students connect the urea cycle to the central metabolic processes of gluconeogenesis and the citric acid cycle. The students use the models to then connect basic nutritional information to the muscle wasting symptoms observed in cancer patients. The direct relevance of the material to nursing students will improved their retention and transfer of the knowledge to later coursework and professional practice.
Correlations between child and parent‐reported pediatric health‐related quality of life in a sample of 7 to 11‐year‐old schoolchildren
Authors: Baker Selena L. , Reidenbach Katherine L. , McCabe Sean D. , Brauchla Mary C. , Kranz Sibylle
Published: June 2021

To date, few studies have examined correlations between child and parent‐proxy responses in healthy populations. We used the PedsQL™ 4.0 Generic Core Scales to assess child‐ and parent‐reported pediatric HRQOL in a sample of 7 to 11‐year‐old schoolchildren at baseline and at completion of an 8‐week intervention study aimed at increasing dietary fiber intake. The PedsQL™ model is comprised of 4 core scales. Responses may be reported as 3 summary scores: total, physical health, and psychosocial health (comprised of emotional, social and school scales). In our study, preliminary data analysis shows the following linear correlation coefficients between child and parent responses:

Parent/Child Correlation Values by Time Point and Treatment

Scale
Baseline
Week 8

Treatment/Control
Treatment/Control

Total Score
0.181/0.221 (n=32/n=28)
0.436/0.698 (n=30/n=24)

Physical Score
0.214/0.091 (n=33/n=28)
0.192/0.387 (n=30/n=24)

Psychosocial Score
0.183/0.354 (n=32/n=28)
0.318/0.669 (n=32/n=30)

With the exception of the treatment group physical score, all correlations were higher at week 8 than at baseline, suggesting that regardless of treatment group, the study may have influenced children's and parents’ awareness/perception of health. The small to medium effect size at baseline is similar to that reported in the literature for a school population of similar age. Research supported by the Kellogg Company.
Constrained maternal agency is associated with poor child feeding practices and child undernutrition: evidence from twelve low‐income countries
Authors: Ickes Scott Bradley , Hurst Taylor , Casey Kerry , Roberts Alison
Published: June 2021

Recent policies have emphasized that increasing women's status is a necessary action to improve child nutrition. However, few studies have examined the effect of women's status on undernutrition across multiple contexts. This study examines the relationship between women's agency, independent of education and income, and child feeding and nutrition in 12 low‐income countries in four world regions (n= 42,677).

Constrained women's agency—limitations on the capacity of women to take action given their assets and capabilities—was associated with inadequate child feeding practices. Women who were underweight were less likely to meet the majority of WHO feeding indicators while those with media access, were involved in household decisions, and were employed were more likely to meet these indicators.

Low maternal agency was associated with greater child undernutrition, while evidence of improved agency reduced the likelihood of undernutrition. Women who were underweight were twice as likely to have an underweight or wasted child, while women who believed domestic abuse was justified were 20% more likely to have a stunted child. Evidence of opportunities for improved agency was associated with improved child nutrition status. Actions to improve women's agency are likely to improve child feeding and prevent under nutrition.

Supported by the Borgenicht Program for Aging Studies.
Unpredicted Growth from Ages 1 to 5 and 5 to 8 Years in Ethiopia, India, Peru and Vietnam: Key Distal Household and Community Factors
Authors: Crookston Benjamin T , Schott Whitney , Lundeen Elizabeth A , Stein Aryeh D , Behrman Jere R
Published: June 2021

Recent research has demonstrated some growth recovery among children stunted at infancy. Less is known about key ages for such growth recovery, and what factors underlie this growth. This study characterized growth from ages 1 to 5 and 5 to 8 years by focusing on growth that was not predicted by initial height‐for‐age z‐score (HAZ), and identified household and community factors associated with these changes using longitudinal data on 7,266 children in the Young Lives (YL) study in Ethiopia, India, Peru and Vietnam. HAZ at age 1 year did not predict 40–70% of variation in HAZ at age 5 years, and HAZ at age 5 years did not predict 26–46% of variation in HAZ at age 8 years. Multiple regression analysis suggested that these unpredicted changes in HAZ were significantly associated with household consumption, maternal height, hospital presence, and, in some cases, caregivers’ schooling, and fathers’ schooling. There was heterogeneity by urban/rural residence and to a limited extent by gender. These results underline the importance of a child's starting point in infancy in determining his or her growth and point to distal household and community factors that may determine growth recovery and growth failure.

Support: Bill & Melinda Gates Foundation, NICHD, DFID and the Netherlands Ministry of Foreign Affairs
Longitudinal associations of blood biomarkers of insulin and glucose metabolism and colorectal cancer risk in the Framingham Heart Study Offspring population (1971–2008)
Authors: Parekh Niyati , Lin Yong , Vadiveloo Maya , Hayes Richard , Lu‐Yao Grace
Published: June 2021

Higher blood glucose is hypothesized to increase colorectal cancer risk. Longitudinal associations of hyperglycemia with incident colorectal cancer were investigated among the Framingham Heart Study Offsprings (n=4192; n events=136; 1971–2008). Fasting insulin and glucose were estimated from blood samples; demographic, smoking, activity and dietary information was obtained during interviews. Time‐dependant survival analyses were used to compute hazard ratios (HR) and 95% confidence interval (CI) for colorectal cancer incidence, using SASv9.2. After adjusting for age, sex, smoking, alcohol and physical activity, hyperglycemia (>;110 mg/dl) was associated with 2.2‐fold increase in risk of incident colorectal cancer (HR: 2.21; CI:1.5–3.2). Risk was approximately 2‐fold higher among persons with hyperinsulinemia (HR:2.1; CI:1.1–3.9) and poor long‐term glycemic control measured by hemoglobin A1c (HR:2.2; CI: 1.1–4.5) for tertile 3 vs. 1 in adjusted models. Additionally, persons with 5–10y, 10–20y, 20+ y of hyperglycemia had a significant 1.8‐, 2.5 and 3.5‐fold increased risk of colorectal cancer, respectively. In conclusion, disturbances in glucose metabolism appear to increase risk of colorectal cancer. These data suggest that risk increases with the duration of exposure to hyperglycemia.
The myth of energy balance: Is food really making children fat?
Authors: Xue Hong , Wu Yang , Chen Hsin‐Jen , Wang Youfa
Published: June 2021

Background

Little research tested the direct effect of energy intake and expenditure to study the causal links between shifts in diet and the increase in childhood obesity in developing world.

Objective

To examine the unique patterns of energy imbalance in China.

Methods

The 1991–2000 nationwide China Health and Nutrition Survey (CHNS) data and quantile regression models (QRM) were used to assess the differential effects of energy intake on weight changes in children (2–18 y) across the weight distribution.

Results

The children's mean body weight (kg) increased 20% between1991–2000, from 30 (95% confidence internal (CI): 29.6, 30.5) to 35.9 (95% CI: 35.5, 36.4). However, the average daily total energy intake (kcal) declined from 2037 (95% CI: 2013, 2062) in 1991 to 1929 (95% CI: 1903, 1956) in 2000. Our model prediction suggested evident gaps between observed and energy intake predicted body weight (2–5 kg lower of observed mean body weight than predicted mean body weight across all age‐gender groups). QRM estimates examining the 50%, 85%, and 95% percentiles of the BMI (kg/m2) distribution suggest an insignificant effect of total energy intake on weight changes in children on the upper tail of the BMI distributions.

Conclusions

Our results suggest food intake along is not the primary driver of the rising childhood obesity epidemic in China.

Grant Funding Source: NIH/NICHD (U54 HD070725‐01)
Non‐responsive feeding behaviors are stable across toddlerhood
Authors: Hurley Kristen M , Tilton Nick , Candelaria Margo , Hager Erin , Latta Laura , Wang Yan , Caulfield Laura , Black Maureen M
Published: June 2021

Objective

To examine patterns of toddler feeding behaviors overtime.

Methods

277 mother‐toddlers pairs were enrolled in a 12–month randomized controlled trial to prevent toddler overweight. Mean maternal feeding behaviors (responsive, forceful, restrictive and indulgent; 5‐point scales) were examined at baseline, 6, and 12‐months post‐recruitment. Maternal depressive symptoms (BDI, 4‐point scale) were evaluated as potential effect modifiers. Mixed effect models (adjusting infant age and intervention status) were employed.

Results

Forceful, restrictive, and indulgent feeding behaviors were stable across toddlerhood (p>;0.05). While responsive feeding was stable among mothers with low depression (p>;0.05), depressed mothers became slightly more responsive, though not enough to make up for baseline difference (β=0.30, p=0.01).

Conclusion

While responsive feeding behaviors are sensitive to maternal depression, non‐responsive behaviors remain constant throughout toddlerhood.
Resistance training improves blood pressure regardless of daily breakfast composition
Authors: Kern Mark , Hobb Kylee , Clayton Zachary , Shelechi Mahshid , Hernandez Lisa M , Barber Anjee , Petrisko Yumi , Hooshmand Shirin , Nemoseck Tricia
Published: June 2021

Resistance training has been consistently demonstrated to reduce blood pressure, even in normotensive individuals; however, less is known about diet/exercise interactions on blood pressure. Our purpose was to examine the effect of resistance training three times per week on blood pressure in 44 normotensive adults aged 18–35 years. Subjects were randomly assigned to consume isoenergetic (400 kcal) breakfasts every day that were either egg‐based (including two eggs per day) bagel‐based. Resistance training included 3–4 sets of 10 exercises of major muscle groups. Each set was performed at 60–90% of one repetition maximum for 8–10 repetitions. Overall, systolic blood pressure decreased (P<.05) from 115+/−21 to 107 +/− 32 mmHg, while diastolic blood pressure decreased (p<.05) from 70 +/− 13 to 63 +/− 19 mmHG. However, no statistically significant changes were detectable within dietary groups after 6 weeks (p‐values were between .07–.15), likely due to relatively low statistical power. In conclusion, six weeks of resistance training three times per week promoted improvements in blood pressure for study participants overall, and dietary composition of breakfast appeared to have little, if any, impact on the outcome. Supported by the Egg Nutrition Center.
Simultaneous analysis of circulating 25‐hydroxy‐vitamin D3, 25‐hydroxy‐vitamin D2, carotenoids, retinoids, tocopherols, and oxidized and reduced coenzyme Q10 by HPLC with photo diode‐array detection using C18 and C30 columns alone or in combination
Authors: Franke Adrian A , Morrison Cynthia , Custer Laurie , Li Xingnan , Lai Jennifer
Published: June 2021

Modern studies require high‐throughput assays that provide many biomarkers from a single specimen. Several circulating lipid‐soluble agents have been shown to serve as useful biomarkers for disease prevention. We aimed to develop a simple, fast, and accurate HPLC‐diode array detection assay to simultaneously measure such agents. A C18 column alone, a C30 column alone, or these connected in series measured 25‐(OH) vitamin D2 and D3, retinol, α, β‐, γ‐ and δ‐tocopherol, all major carotenoids and their isomers, and ubiquinol‐10 and ubiquinone‐10 in a single chromatographic run. The C18 column alone resolved all analytes except the D vitamers and lycopene isomers and co‐eluted lutein with zeaxanthin and β‐ with γ‐tocopherol. The C30 column alone resolved all carotenoids and many of its isomers, β‐ and γ‐ tocopherol, and D vitamers but not the Q10 compounds. Connecting the C18 and C30 column in series with a DAD both between and after the columns resolved all analytes but the run time was unacceptably long (90 mins). This serial connection of columns but with only one DAD and a 6‐port valve between the columns resolved all analytes in 45 mins. Shortening run times in any system resulted in the resolution of fewer analytes. Our proposed methods can be custom designed to meet the specific needs of projects depending on analyte requirements (www.uhcancercenter.org/analyticallab). Supported by NCI Grant P30 CA 717890.
Bioprocessing of Aleurone Improves In Vitro Bioaccessibility and Caco‐2 Accumulation of Ferulic Acid
Authors: Moser Sydney Elizabeth , Garcia‐Campayo Vicenta , Aimutis William R. , Ferruzzi Mario G.
Published: June 2021

Ferulic acid (FA), a phenolic acid primarily located within the aleurone layer of wheat bran has demonstrated anti‐inflammatory activity in vitro. However, bioavailability of FA from wheat bran is reported to be low, creating interest in processing methods to increase digestive release (bioaccessibility) of FA. The purpose of this study was to assess FA bioaccessibility from wheat bran (red and white), aleurone (milled to <90 and 125–250μm), and aleurone treated with exogenous xylanase + FA esterase using an in vitro digestion/Caco‐2 human intestinal cell model. We hypothesized that processing would increase bioaccessibility and intestinal uptake of FA from aleurone compared to bran. Following in vitro digestion, relative bioaccessibililty of FA did not differ between aleurone and bran but absolute bioaccessibility was higher from aleurone samples (1.56–1.85 compared to 0.55–0.69μg/g of material). Enzymatic treatment of aleurone increased relative (0.67 to 3.4%) and absolute (1.56 to 7.98μg/g) bioaccessibility, as well as peak Caco‐2 accumulation of FA (11.7 to 64.6pg/mg protein) in comparison to untreated aleurone. These results suggest that enzymatic treatment may be effective at increasing the bioavailability of FA from aleurone. Financial support of this research was provided by Cargill Inc.
Inhibition of Streptococcus mutans amyloid fibril formation by cranberry fractions
Authors: Adamec Asher B , Helm Kyle P , Crowley Paula J , Brady L Jeannine , Percival Susan S
Published: June 2021

Biofilm formation is necessary to establish urinary tract infections, dental caries and numerous other infectious conditions. S. mutans is an organism that forms biofilms and was recently shown to be an amyloid‐forming organism. Amyloids are insoluble fibrillar protein aggregates that have been associated with protein malfolding in disease states such as Alzheimer's, but the concept of functional amyloid formation as a directed process involved in microbial pathogenesis is recently emerging. A panel of well‐characterized cranberry fractions (OSC Inc) was tested to determine if they inhibited S. mutans biofilm formation. The fractions did not affect bacterial growth, but inhibited biofilm formation. As a potential mechanism of biofilm inhibition, amyloid fibrillization by S.mutans extracellular proteins was assessed using a Thioflavin‐T fluorescence assay. Amyloid formation was inhibited by cranberry fractions containing proanthocyanidins. Thus, cranberry bioactive compounds may inhibit biofilm formation by preventing amyloid fibril development of the amyloidogenic proteins produced by S. mutans. Support by Univ Schol Prog, UFL, and NIDCR R01DE21789
Citrus and berry flavonoids inhibit dipeptidyl peptidase‐IV enzymatic activity by binding to the catalytic site
Authors: Fan Junfeng , Johnson Michelle , de Mejia Elvira Gonzalez
Published: June 2021

We investigated 25 citrus and berry flavonoids on inhibition of DPP‐IV, contributing to decrease glucose absorption. Heperetin, nobiletin, tangeretin, cyanidin, petunidin, genistein and EGCG could bind to DPP‐IV active sites. Binding energies (kcal/mol), hesperetin (−5.8), nobiletin (−5.7), petunidin (−5.1) and tangeretin (− 4.9) were lower than diprotin A (−4.8), indicating more potency in inhibiting DPP‐IV. This was attributed to H bonds between hydroxyl groups on flavone aromatic rings and amino acid residues in the enzyme, and đ‐interactions of flavonoids aromatic ring B and DPP‐IV arg125, phe357 and arg669. Aglycone flavonoids (luteolin, apigenin, quercetin, kaempferol, flavone, naringenin, catechin, gallocatechin, epicatechin) and glycosylated flavonoids (cyanidin‐3‐glucoside, delphinidin‐3‐glucoside, dephinidin‐3‐ arabinoside, malvinidin‐3‐galactoside, malvinidin‐3‐arabinoside) could bind their aromatic B‐ring to DPP‐IV active sites, inhibiting its activity. Flavonoinds with disaccharides (naringin, rutin and narirutin) could not bind DPP‐IV due to unfavorable sugars steric obstacle. Biochemical kinetics showed blueberry and blackberry anthocyanins effectively reduced DPP‐IV activity (IC50 4.0 μM C3G), comparable to the known inhibitor (IC50 4.3 mg/mL). Citrus and berry flavonoids can bind DPP‐IV active pockets with potential as antidiabetes therapy.

USDA
High ferritin and low folate increases PBMCs genomic DNA methylation in association with SHMT1–1420TT variant
Authors: Moruzzi Sara , Guarini Patrizia , Udali Silvia , Olivieri Oliviero , Girelli Domenico , Pattini Patrizia , Pizzolo Francesca , Choi Sang Woon , Friso Simonetta
Published: June 2021

Nutrient‐gene interactions within one‐carbon metabolism modulate DNA methylation, the major potentially reversible epigenetic modification in eukaryotic cells. The cytosolic serine hydroxymethyltransferase (SHMT1) regulates the metabolic balance between nucleotide synthesis and methylation in one‐carbon pathway. The SHMT1–1420T allele has been associated with a reduced enzyme activity and a decreased risk of cancer. By enhancing SHMT1expression, ferritin affects folate‐mediated one‐carbon metabolism.

Aim of this study was to analyze how the interaction among ferritin, folate and SHMT1‐1420C>;T polymorphism may affect peripheral blood mononuclear cells (PBMCs) DNA methylation (LC/ESI/MS method) in 537 subjects enrolled in the Verona Heart Study to identify a possible biomarker for cancer.

Results showed that SHMT1‐TT carriers, under a high ferritin/low folate condition, show significantly increased PBMCs genomic DNA methylation than SHMT1‐CC subjects (P=0.01).

Since cancer is usually associated with genomic hypomethylation, the increased genomic methylation in SHMT1–1420TT genotypes in presence of high ferritin/low folate, could be potentially protective for cancer risk.
Autocrine regulation of endothelial barrier integrity by CAP37
Authors: Fox Elizabeth , Pereira Anne , Reichner Jonathan
Published: June 2021

BACKGROUND

CAP37 is a peptide released by neutrophils upon stimulation of β2 integrins. Its effects include increased ICAM‐1 expression and endothelial cell cytoskeleton reorganization. Previous work has shown that endothelial cells may produce CAP37. We sought to determine the effect of neutralization of CAP37 on endothelial monolayer resistance.

METHODS

Human umbilical vein endothelial cells (HUVECs) were grown to confluence and activated with TNFα for six hours. Two mouse‐derived monoclonal anti‐CAP37 antibodies (B1B5 and D5F10) were applied to the monolayer. The effect on endothelial barrier function was determined using Electric Cell‐substrate Impedance Sensing (ECIS). Barrier function of the monolayer was expressed as a fraction of pre‐treatment resistance values.

RESULTS

Both antibodies caused a biphasic change in monolayer resistance. Within 30 minutes, resistance increased to a peak of 1.16+/−0.04 (B1B5 [p<0.0001 vs. IgG control]) and 1.12+/−0.11 (D5F10 [p=0.03 vs. IgG control]). After this initial peak, resistance progressively decreased, with endothelial barrier integrity falling below 50% of the pre‐treatment value within 5 hours.

CONCLUSIONS

Neutralization of CAP37 causes a change in endothelial barrier function. This occurs in the absence of leukocytes, demonstrating the role of CAP37 in the autocrine regulation of endothelial monolayer integrity, and suggesting a potential therapeutic target. Future work will include further characterization of endothelial cell CAP37. (NIH GM066194)
Analysis of ligands for CD83, a marker of activated immune cells
Authors: Ando Yusuke , Oku Teruaki , Tsuiji Makoto , Tsuji Tsutomu
Published: June 2021

CD83, a member of the immunoglobulin superfamily, is a type‐1 transmembrane glycoprotein and expressed on various activated immune cells. The soluble form of CD83 strongly suppresses mixed lymphocyte reaction (MLR) and experimental autoimmune encephalomyelitis (EAE), however, the mechanism of CD83‐mediated immune regulation including ligands for CD83 (CD83L) has not been elucidated. By flow cytometry using the CD83‐Fc fusion protein, we screened immune cells from mouse lymphoid organs to identify CD83L+ cells and found that CD83‐Fc bound to B220int IgMhi CD11b+ peritoneal B‐1 B cells, but not to cells from spleen, bone marrow, or thymus. When we tested the binding of CD83‐Fc to various B lymphocytic cell lines, the fusion protein bound to BCL1‐B20 cells which are known to be derived from B‐1 B cells. The pull‐down assay using CD83‐Fc revealed that a part of glycosylated IgM heavy chain was precipitated from the crude membrane fraction of BCL1‐B20 cells. Furthermore, anti‐mouse IgM antibodies blocked binding of CD83‐Fc to B‐1 B cells and BCL1‐B20 cells. These results suggest that CD83+ cells might recognize surface IgM with unique glycosylation expressed on B‐1 B cells during immune responses.
Effects of Maternal Ethanol Intake during the Pregnancy and Lactation on the Expression of AMPA Receptors in Hippocampus of Pups at Different Stages of Brain Development
Authors: Mussi Sara Eleodoro , Fiorillo Henrique Mascioli , Cheregatto Nathálie Neves , Soler João Antônio , Iyomasa Melina Mizusaki , Rosa Maria Luiza Nunes Mamede
Published: June 2021

Aim

To investigate whether ethanol consumption during pregnancy and lactation might induce changes on the expression of GluR1 and GluR2 in the hippocampus of pups at different stages of brain development. Female rats were exposed to water (control, n=8) or ethanol 10% (alcoholic, n=8) for 60 days, from mating to weaning. The pups were studied at PND30–90 (n=8–13). Immunohistochemistry. Positive cells were quantified. ANOVA. Alcoholic pups showed reduction in GluR1 expression in CA1 and HDG (23–51%, p<0,001) at all stages of development, while in CA3 the reduction was found only at PND21 and 30 (50%, p<0,001). Comparisons within the same treatment showed both increase and decrease in GluR1 along the development in controls while predominant increase was found in alcoholic pups (33–163%, p<0,001). GluR2 expression was reduced only in CA1 of alcoholic pups at PND60 (25%) and 90 (16%) (p<0,001), and increased in CA3 at PND60 (86%, p<0,001). Within the same treatment, GluR2 expression in controls or alcoholic pups in different stages of development showed an increase in CA1 (33–78%), a decrease in CA3 (25–50%) and both in HDG (19–67%) (p<0,001). Maternal ethanol intake during pregnancy and lactation induces changes in glutamatergic neurotransmission in the pups brains through the AMPA receptors, which may implicate the normal development of brain regions crucial for learning and memory functions. Support: FPA.