bluuebunny/crossref_metadata_2025 huggingface dataset:
Inclusion of Surface Anatomy in an Integrated Medical Curriculum: A Hands‐on Experience.
Authors: Bacro Thierry
Published: June 2021

The importance of including learning experiences designed to facilitate the acquisition of surface anatomy skills has become a pillar of the modern medical and health professional curricula promoting the integration of basic sciences knowledge with clinical sciences. Acquiring surface anatomy palpatory skills however is a time consuming and challenging endeavor in educational centers teaching large classes. Educators have developed a variety of strategies to achieve their goals, including the coordination of clinical activities with cadaver dissection and the use of virtual reality simulation to train students in palpatory diagnosis as shown in the other presentations in this refresher course. Over the last ten years, educators involved in the teaching of surface anatomy at the Medical University of South Carolina have developed a database of digital resources in the form of still pictures and mini‐videos clips to promote the teaching of surface anatomy. During this session, a selection of mini‐clips will be shown to the audience and time will be dedicated to the self‐palpation of clinically relevant anatomical structures of the upper limb by the participants themselves, illustrating how students can use these digital resources to strengthen their clinical skills.
A novel mode for regulation of translesion DNA polymerases in early C. elegans embryos
Authors: Michael W. Matthew , Kim Seung‐Hwan , Holway Antonia
Published: June 2021

Much of what we have learned about DNA damage response pathways has come from the study of homogenous populations of cells growing in culture, namely yeasts and mammalian tissue culture cells. Although these systems have been extremely informative in describing how individual DNA damage response pathways function, they are by their nature unable to lend insight into how these pathways interact with one another in the context of multi‐cellular organisms, and during different phases of animal development. We have been studying how early C. elegans embryos respond to DNA damage, and the results have revealed insights that were unexpected based on paradigms established by studies on cultured cells. Specifically, we have found that early embryos actively suppress activation of the ATR‐dependent checkpoint during a DNA damage response. To do so, embryos employ a robust capacity for translesion DNA synthesis, an inherently mutagenic process, so that replication is not slowed, even when chromosomes are heavily damaged. We have also discovered a novel regulatory system that limits the amount of DNA that is replicated by translesion DNA polymerases during a damage response. Our results suggest that translesion synthesis assumes an unusually prominent role during an early embryonic DNA damage response, and that to buffer themselves against the deleterious consequences of translesion synthesis, embryos have evolved a regulatory system that limits replication by these mutagenic polymerases. In a more general sense, our results suggest that continued study of DNA damage response pathways in multi‐ and heterogeneous cell systems will uncover further surprises and examples where the “rule book” seems to have been discarded.
Contribution of enhancer sequences and spliceosomal core components to substrate positioning for splicing catalysis
Authors: Konarska Magda , Templeton Richard , Lisanti Antonella , Pani Bibhusita , Kostyukovskiy Ilya
Published: June 2021

One of the main questions in the splicing field concerns the nature of the catalytic center of the spliceosome. To investigate the mechanism of splice site (SS) selection, and in particular the role of 5′ exon interactions in positioning the 5′SS for catalysis, we carried out a genetic screen in yeast to identify exon sequences capable of compensating for 1st step splicing defects. We identified several classes of yeast exon and intron enhancers that are strikingly similar to known metazoan motifs: AC‐rich and purine‐rich enhancers, hnRNP A1‐binding sites, and poly‐pyrimidine tracts. These results reveal a fundamental similarity of splicing regulation between yeast and metazoan systems and suggest that splicing enhancers represent sequences that are recognized multiple times during spliceosome assembly and catalysis, affecting multiple highly conserved interactions that modulate spliceosome formation and catalytic function.

In a complementary approach, we monitor the contribution of spliceosomal components to positioning of the substrate. Using reporters with an unconventional, suboptimal 5′SS, we have screened for and identified spliceosomal mutants that favor an altered 5′SS positioning. These experiments form part of a broader direction of developing orthogonal spliceosome systems, in which selected spliceosome mutants function only in the context of a specialized, orthogonal substrate.
Constraining errors in splice site choice
Authors: Staley Jonathan P. , Koodathingal Prakash , Mayas Rabiah M. , Maita Hiroshi , Semlow Daniel R. , Novak Thaddeus , Piccirilli Joseph A.
Published: June 2021

While even single nucleotide errors in pre‐mRNA splicing can lead to catastrophic consequences, our understanding of fidelity mechanisms in splicing is poor. Genetics studies have established the importance of fidelity mechanisms in splicing and implicated 3 of the 8 spliceosomal DExD/H box ATPases in competing with splicing to enable kinetic proofreading. However, due to a paucity of in vitro assays, it has remained unclear how specificity is established by kinetic proofreading and how rejected substrates are discarded. We have established in vitro that each chemical step in splicing is proofread by a DEAH box ATPase – 5′ splice site cleavage is proofread by Prp16 and exon ligation is proofread by Prp22. In a kinetic proofreading mechanism, specificity can be achieved if the rate of the ATPase and/or the rate of the proofread step varies with the authenticity of the substrate. We have found evidence that both Prp16 and Prp22 enhance specificity by discriminating against slowly splicing substrates. Both Prp16 and Prp22 reject substrates reversibly, necessitating an independent discard activity that we attribute to the DEAH box ATPase Prp43, which normally functions to discard a genuine intron after excision from the precursor. These findings establish that both chemical steps in splicing are proofread by a common ATP‐dependent framework and support a general role for DExD/H box ATPases in fidelity. Support: ACS, NIH.
Oral Tolerance Reduces Pulmonary Inflammation in a Cockroach Antigen Murine Model of Allergic Asthma
Authors: Vaickus Louis Joseph , Natarajan Sudha , Bouchard Jacqueline , Kim Jiyoun , Remick Daniel G.
Published: June 2021

Our lab previously demonstrated that German cockroach allergens (CRA) induce allergic‐type airways inflammation in outbred (ICR:CD‐1) mice which closely resembles human allergic asthma. We determined the efficacy of oral tolerization in alleviating asthmatic symptoms. Mice were given 8ug/day CRA by oral gavage for 4 days beginning with day ‐7, followed by intratracheal challenges with 4.75ug on day 0 and 2.4ug on days 14 and 21. Cytokines and cells were measured in the bronchoalveolar lavage (BAL) fluid and cytokines and myeloperoxidase activity were measured in lung homogenate. Samples were collected 4 hours post final challenge and the results compared to PBS fed, CRA challenged mice. BAL eosinophils were significantly reduced in the CRA fed mice and eosinophil specific peroxidase activity was reduced in the lung homogenate as compared to PBS fed mice. In addition, multiple respiratory factors were significantly improved in the orally tolerized mice. These results indicate that oral tolerance abrogates eosinophil infiltration into the lung space. These beneficial effects are reflected by an improvement in pulmonary health as evaluated by respiratory parameters.

BAL eosinophils and eosinophil specific peroxidase activity in the lung homogenate. Respiratory parameters, respiratory rate (RR), minute ventilation (MV), peak inspiratory flow (PIF), time of expiration (Te), time of inspiration (Ti), enhanced pause (Penh).

BAL Eos
EPO
RR
MV
PIF
Te
Ti
Penh

CRA Fed
43,300
0.6
273.9
84.9
5.9
0.15
0.09
2.3

PBS Fed
158,800
1.2
223.2
67.8
4.8
0.2
0.11
3.9

p value
0.007
0.02
0.01
0.01
0.002
0.04
0.002
0.03
Requirement for iNOS in chronic allergen exposure‐induced pulmonary fibrosis but not inflammation or mucus production: Specific implications of TGF‐b, TIMP‐2, and arginase‐2 expression
Authors: Naura Amarjit S , Zerfaoui Mourad , Kim Hogyoung , Hans Chetan , Ju Jihang , Rodriguez Paulo C , Park Jiwon , Ochoa Augusto C , Boulares Hamid A
Published: June 2021

The exact role of iNOS in allergic airway inflammation continues to be elusive. Here we tested the hypothesis that iNOS plays different roles during acute vs. chronic inflammation. We show that iNOS knockout (KO) was associated with reduction in eosinophilia, IL‐13 and mucus production upon acute exposure to OVA (allergen). Such protection was abolished upon chronic exposures to OVA. Interestingly, pulmonary fibrosis observed in WT mice under the chronic protocol was absent in iNOS‐KO mice despite persistent IL‐13 production. Such protection was associated with reduced collagen synthesis and an indirect TGF‐b modulation as confirmed using primary lung smooth muscle cells (LSMCs). Although the active forms of MMP‐2/‐9 exhibited little change, the large TIMP‐2 increase detected in WT mice was absent in the iNOS‐KO counterparts. The regulatory effect of iNOS on TIMP‐2 may be mediated directly by peroxynitrite as the latter reversed TIMP‐2 expression in iNOS‐KO LSMCs. These results suggest that the iNOS‐TIMP‐2 link may explain the protective effect of iNOS KO against pulmonary fibrosis. Lung sections from chronically OVA‐exposed iNOS‐KO mice exhibited evidence of residual but significant protein nitration, prevalent oxidative‐DNA damage and PARP‐1 activation. Such tissue damage, inflammatory cell recruitment and mucus hypersecretion may be the result of a substantial Arginase‐2 expression and activity. These results exemplify the complexity of the role of iNOS in asthma and its potential as a therapeutic target.
Mechanism of Chromatin Remodeling and Recovery During Passage of RNA Polymerase II
Authors: Studitsky Vasily M , Kulaeva Olga , Gaykalova Daria , Pestov Nikolai , Golovastov Viktor , Vassylyev Dmitry , Artsimovitch Irina
Published: June 2021

Transcription of eukaryotic genes by RNA polymerase II (Pol II) is typically accompanied by nucleosome survival and minimal exchange of histones H3/H4. The mechanism of survival and recovery of chromatin structure remains obscure. In our recent studies we have shown how transcription through chromatin by Pol II is uniquely coupled with nucleosome survival. Structural modeling and functional analysis of the intermediates of transcription through a nucleosome was conducted. When Pol II approaches the area of strong DNA‐histone interactions, a small intranucleosomal DNA loop (zero‐size or Ø‐loop) containing transcribing enzyme is formed. During formation of the Ø‐loop, the recovery of DNA‐histone interactions behind Pol II is tightly coupled with their disruption ahead of the enzyme. This coupling is a distinct feature of the Pol II‐type mechanism that allows further transcription through the nucleosome, prevents nucleosome translocation and minimizes displacement of H3/H4 histones from DNA during enzyme passage.
Treatment in the Context of Other Diseases
Authors: Nesbitt Shawna
Published: June 2021

Hypertension is present in nearly 30% of US adults and it accounts for many visits to physicians. It contributes to 77% of first strokes, 69% of first myocardial infarctions, and cost $66.4 billion. The onset of hypertension occurs in middle age most often and increases with aging. In Framingham, hypertension frequently occurs in the setting of other cardiovascular risk factors. Similarly in prehypertension as shown in the TROPHY study, elevated blood pressure rarely occurs without concurrent risk factors. Seventy three percent of type 2 diabetics have hypertension, and it is the second leading cause of renal failure. Thus treating hypertension in the setting of other diseases is increasingly more common. In addition, noncardiovascular diseases such as gout, asthma and arthritis frequently coexist in these patients. As mortality has improved in diseases such as cancer and HIV, chronic medical conditions such as hypertension have become prominent. While the etiology of these diseases is not related, the treatment for these conditions may affect blood pressure or its treatment. There are specific indications for various classes of antihypertensives. Clinical trial data suggest that most hypertensives require more than 2 medications. In addition, hypertensive medications have some synergy between specific agents. This requires thoughtful consideration on the selection of agents for complex patients.
gene‐centered regulatory networks
Authors: Walhout Marian
Published: June 2021

The expression of each of our ~25,000 genes in different tissues or under different conditions is critical for our proper development and function. Indeed, changes in gene expression caused by mutations in transcription factors (TFs) or the cis‐regulatory genomic DNA elements they bind to (TF binding sites, or TFBSs) can result in a variety of human diseases. In order to fully understand development and pathologies, and to design effective therapeutics it is critical to understand which TF regulates the expression of which gene, where and under which conditions. In addition, it is essential to know the elements each TF binds to and where in the genome these TFBSs are located. This is a major challenge in genomic science as very little is known about the targets, binding sites, transcriptional activity and biological function for the majority of metazoan TFs. We use the nematode C. elegans to address this challenge. The C. elegans genome contains ~20,000 protein‐coding genes, 940 of which we predict encode regulatory TFs. We use gene‐centered, rather than TF‐centered (e.g. ChIP), protein‐DNA interaction mapping methods to map gene regulatory networks. We then integrate these networks with other networks and data types and analyze how regulatory networks and their properties relate to healthy as well as pathological system states. Progress on network mapping and characterization will be discussed.
Human antioxidant status is not altered by quercetin supplementation
Authors: Shanely R. Andrew , Knab Amy M. , Nieman David C. , Jin Fuxia , McAnulty Steven R. , Landram Michael J.
Published: June 2021

The purpose of this study was to measure the influence of ingesting quercetin for 12 weeks at two doses relative to placebo on plasma measures for oxidative stress and antioxidant capacity in a large community group of male (40%) and female (60% female) subjects (N=1,002) varying widely in age (18 to 85 years) and body mass index (BMI) (16.7 to 52.7 kg/m2). Subjects were randomized to one of three groups, with supplements administered using double blinded procedures: Q‐500 (500 mg quercetin/day), Q‐1000 (1000 mg quercetin/day), or placebo (PL). Fasting blood samples were obtained pre‐ and post‐study. Plasma quercetin in Q‐500 and Q‐1000 increased significantly above PL, and monthly measures on a subset of subjects found that the increase peaked during the first month and was maintained for 12‐weeks. Plasma F2‐isoprostanes, oxidized low density lipoprotein (oxLDL), reduced glutathione (GSH), ferric reducing ability of plasma (FRAP), and oxygen radical absorbance capacity (ORAC) did not differ between supplementation groups, even after adjustment for gender, age, BMI, and disease status. In summary, quercetin supplementation, 500 mg or 1000 mg/day, for 12 weeks significantly increased plasma quercetin levels in a dose‐responsive manner, but did not influence several measures of oxidative stress and antioxidant capacity.

Supported by grants from Coca‐Cola and Quercegen Pharma.
Smarter Lunchrooms: Payment Systems that Nudge Healthier School Lunch Choices
Authors: Wansink Brian , Just David R. , Payne Collin R.
Published: June 2021

How can increasingly scrutinized school lunch programs encourage children to make better food choices? Placing restrictions on the use of prepaid lunch accounts use may influence nutritious food selection without eliminating free choice or reducing profitability.

A controlled field experiment in a school lunch cafeteria involved 166 students with a modal age of 19‐years. These students were allowed to purchase their lunch in one of three ways: 1) cash only, 2) cash and an unrestricted debit card, or 3) cash and a restricted debit card that could be used to purchase items marked as healthy. Their selection of items and intake was measured, and follow‐up questions were asked.

Those given restricted debit cards ate significantly fewer calories than those given the unrestricted card 517.3 p=0.045), and a much higher percentage of what they selected and consumed were healthy foods compared to both those given an unrestricted debit card and those given cash (78.6%, p=0.000).

This cross‐sectional study of older teenagers shows that restricting prepaid lunch cards to foods marked as reasonably healthy dramatically improved nutritious food choice and consumption. Because this payment procedure still allowed students to use their own cash to purchase less healthy options, it did not unduly restrict dining options or reduce cafeteria revenue.
Macrophage Endothelial Lipase Expression is Regulated by Fatty Acids and PPAR gamma Expression
Authors: Jung Un Ju , Torrejon Claudia , Hamai Hiroko , Deckelbaum Richard J.
Published: June 2021

Macrophages within atherosclerotic lesions highly express endothelial lipase (EL) and PPARγ. We previously demonstrated that a saturated fatty acid (FA), palmitic acid (PA), increased macrophage EL mRNA and protein expression, whereas a n‐3 FA, EPA, inhibited the higher expression induced by LPS and PA. We now explored mechanisms by which EPA, in contrast to PA, lowers EL expression in macrophages. Murine J774 and elicited peritoneal macrophages (PM, from C57BL/6 mice) were cultured with 50–300 μM of EPA or PA for 7–24h in the presence or absence of a PPARγ agonist or antagonist. PPARγ mRNA levels were significantly increased by PA (4 fold, p<0.01), whereas EPA abrogated effects of LPS on increasing PPARγ mRNA. PPARγ mRNA positively correlated with EL mRNA expression in J774 and PM (r=0.339, p<0.05; r=0.428, p<0.01, respectively). PPARγ activation by rosiglitazone (a PPARγ agonist) increased EL mRNA (8 fold, p<0.01) and protein expression (2 fold, p<0.01), whereas GW9662 (a PPARγ antagonist) abrogated the stimulation of both rosiglitazone and PA. EPA blocked the increase of EL expression caused by rosiglitazone. Thus, EL expression closely linked to PPARγ expression, and this macrophage‐derived lipase is regulated by fatty acids, in part, through modifying macrophage PPARγ expression.

Grant Funding Source: HL40404
Acute Response of Equicaloric Test Meals Varying in Glycemic Index and Glycemic Load on Postprandial Glycemia, Arterial Stiffness and Blood Pressure in Healthy Adults
Authors: Jenkins Alexandra , Bateman Emma , Brissette Christy , Guendelman Yael , Fairgrieve Christopher , Vuksan Vladimir
Published: June 2021

Objectives

The relative importance of the type of carbohydrate (Glycemic Index, GI) and/or the quantity (Glycemic Load, GL) in the context of a mixed meal on glycemia is still debated; whereas the effects on vascular health are unknown. This study therefore investigated the acute effect all 4 permutations of high and low GI and GL meals on postprandial glycemia and vascular function.

Methods

A total of 15 healthy subjects were recruited; preliminary data on the first eight are presented (3M, 5F; age 33 ± 16 y; BMI 21.6 ± 2.7 kg/m2). On 4 separate occasions, subjects received 4 equicaloric meals where the GI and GL levels were manipulated in a block design. Capillary blood samples were collected at fasting and 15, 30, 45, 60, 90, 120, 180 and 240 minutes post‐consumption. Aortic augmentation index (AIx) and central BP were measured hourly using applanation tonometry by radial pulse wave analysis and peripheral BP was evaluated oscillometrically.

Results

The iAUC blood glucose response after the HiGI‐HiGL and LoGI‐HiGL meals were significantly higher than the LoGI‐LoGL and HiGI‐LoGL meals (p<0.0001), while AIx was significantly reduced at 60min after the HiGI‐LoGL and LowGI‐HiGL meals compared to HiGI‐HiGL (p<0.05).

Conclusions

Preliminary data analysis demonstrates that manipulating the GI and GL of a meal result in significantly different blood glucose responses and may acutely modulate vascular function.
Magnesium (Mg) supplementation improves magnesium status and decreases elevated C‐reactive protein in adults older than 51 years with poor quality sleep
Authors: Nielsen Forrest H. , Johnson LuAnn K.
Published: June 2021

NHANES data indicate that two‐thirds of U.S. adults consume less than the RDA for Mg. A low Mg intake or status has been associated with poor quality sleep and inflammatory stress. Thus, 100 adults (22 males and 78 females) older than 51 yr with a Pittsburgh Sleep Quality Index (PSQI) higher than 5 were randomly assigned to 2 groups matched by gender, age, and overall PSQI score. After baseline assessment (wk 1), one group was given a 300 mg/d Mg supplement as Mg citrate, and the other a sodium citrate placebo, for 7 wk. Final assessments were made 5 and 7 wk after supplement initiation for 96 subjects that completed the study as designed. PSQI improved (10.4 to 6.6, p<0.0001) and erythrocyte Mg increased (4.75 to 5.05 pg/cell) regardless of Mg or placebo supplementation. The erythrocyte Mg increase was ~70% greater with Mg supplementation (4.72 to 5.15 vs. 4.78 to 4.94 pg/cell). Mg supplementation reduced plasma C‐reactive protein in subjects with baseline values >3.0 mg/dL; these subjects also had a higher body mass index. Baseline serum Mg was below normal (<1.8 mg/dL) in 37 subjects. Analysis of these subjects found that serum Mg and calcium (Ca) were significantly increased with the increases more marked with Mg‐supplementation (Ca, 8.36 to 8.74 vs. 8.43 to 8.52 mg/dL; Mg 1.69 to 1.82 vs. 1.69 to 1.73 mg/dL). Findings indicate that Mg status of many older individuals could be improved. (Supported by Tyrase Research, Grand Forks, ND)
Isoflavone‐free soy protein diet inhibits LPS‐induced inflammatory responses
Authors: Goodwin Van B , Greenway Amy , Nagarajan Shanmugam
Published: June 2021

Recently, we showed reduced atherosclerotic lesions in a hyperlipidemic mouse model fed isoflavone‐free soy protein diet (SPI−) compared to casein (CAS)‐fed mice, despite unchanged serum lipid levels. However, the molecular mechanisms contributing to the atheroprotective effect of soy‐based diets is not clear. Atherosclerosis is a chronic inflammatory disease and interactions between endothelial cells and monocytes play a pivotal role in the initiation of atherosclerosis. We hypothesize that soy protein/peptides (SPI−) exert their protective effect by inhibiting inflammatory responses contributing to both acute and chronic inflammatory conditions. To address this hypothesis, a LPS‐induced acute inflammation model in apoE−/− mouse was developed. Dose response studies showed LPS at 20 μg/mouse is sufficient to induce CD54 and CD106, key endothelial cell adhesion molecules, expression in mouse aorta. Western blot analysis showed that aortas of SPI−‐fed mice had reduced expression of CD106 compared to aortas of casein‐fed mice. Further, quantitative RT‐PCR analyses of proximal aorta also showed reduced CD106 mRNA expression in SPI−‐fed compared to casein‐fed mice. These findings suggest that the atheroprotective effect of isoflavone free soy diet is mediated, in part, by blocking inflammatory responses associated with atherosclerosis. USDA‐CRIS‐6251‐5100002‐06S.
Brain activation patterns in response to normal vs. protein‐rich breakfast meals in overweight and obese ‘breakfast skipping’ adolescent girls
Authors: Harris Corey T. , Leidy Heather J.
Published: June 2021

Purpose

To examine the brain activation responses to visual food cues in ‘breakfast skipping’ adolescents before and after the daily incorporation of 500 kcal breakfast meals containing either normal protein (NP) (15% of energy as pro) or higher protein (HP) (40% of energy as pro).

Methods

12 overweight/obese adolescent girls (age 15 ± 1 y; BMI 93 ± 1.3%ile; skip breakfast 6 ± 1 times/week) completed a baseline (‘breakfast skipping’, BS) testing day then randomly consumed NP or HP breakfast meals at home for six consecutive days. On day seven of each breakfast pattern, the subjects came to the laboratory to consume their respective breakfast meal followed by an fMRI brain scan prior to lunch (i.e., 3‐h post‐breakfast).

Results

Both breakfast meals led to reductions in brain activation in the prefrontal cortex, cingulated gyrus, and parahippocampal gyrus compared to BS (all regions, P <0.001). In addition to these responses, the PN meal also led to reductions in brain activation in the amygdala (P<0.001), whereas the PR meal led to reductions in the insula (P<0.001).

Conclusion

The daily addition of breakfast led to reductions in brain activation in specific brain regions associated with food motivation and reward in overweight and obese ‘breakfast skipping’ adolescent girls with differential responses attributable to the dietary protein of the breakfast meal. Support: NIH‐5 K12 HD052027‐04

Grant Funding Source: NIH‐5 K12 HD052027‐04
Differences of digestive kinetics of whey and casein are not linked to satiety and gastrointestinal hormone secretions in humans
Authors: Chevalier Laure , Marsset‐Baglieri Agnès , Bos Cécile , Pedersen Camilla , Airinei Gheorghe , Tomé Daniel , Benamouzig Robert , Fromentin Gilles , Gaudichon Claire
Published: June 2021

To verify whether digestion kinetics influence the satiating effect of proteins, we measured digestive kinetics, hormonal secretions and satiety in humans after the ingestion of caseins or whey proteins. Satiety was studied in 37 overweight subjects. On the 1st day, they received a control liquid snack containing 60 g of carbohydrates. Satiety scores and the delay between the snack and the spontaneous demand for lunch were recorded. Subjects were then adapted to consume daily a protein liquid snack containing 30 g of carbohydrates and 30 g of caseins (n=18) or whey proteins (n=19) for 7 days. A 2nd satiety test was realized after the ingestion of the protein snack. Two days later, 15 of the subjects were equipped with a jejunal tube and a venous catheter. Digestive kinetics and plasma hormone concentrations were studied after the ingestion of their snack meal. Compared to the control snack, proteins tended to increase the delay between the snack and the lunch (+ 13±13min, p=0.06), without any difference between groups. The protein snack did not elicit significant secretion of PYY, GLP1 and glucagon from the baseline. Whey proteins were totally delivered to the intestine within 2 h after the meal whereas 5 h were required for caseins. Important modulations in digestive kinetics of dietary protein do not translate into satiety signals or intestinal hormone production in overweight subjects adapted to their protein snack.
Supplementation with bovine colostrum enhances natural killer cell activity in influenza‐infected mice
Authors: Wong Eric B , Ritz Barry W
Published: June 2021

Bovine colostrum (BC), from the first milking following partuition, is available as a human nutraceutical for immune support, although data are limited. Oral administration of BC in mice has been demonstrated to affect local intestinal immunity, including an increase in the percentage of NK cells; however, resistance to infection has not been studied. Therefore, we proposed to investigate the effects of BC (W150, La Belle, Inc.) on the innate immune response to influenza infection in 4 month‐old female C57BL/6 mice supplemented with 1g of BC/kg of body weight by pipette for 7 days prior to and following a non‐lethal infection with mouse‐adapted influenza A virus (H1N1, PR8). Animals were observed through 3 days of infection and assessed for weight loss and recovery, lung virus titers, splenic NK cell activity and serum IgA. BC‐supplemented mice demonstrated less reduction in body weight and decreased lung virus burden following infection compared to controls, indicating a less severe infection. BC‐supplemented mice also demonstrated a significant increase in influenza‐enhanced NK cell cytotoxicity compared to controls at 3 days post‐infection (P<0.05). There were no differences in IgA levels between groups. BC supplementation enhanced NK cell cytotoxicity and improved the immune response to influenza virus infection in mice, with no effect on serum IgA. (Sponsored by La Belle, Inc., Bellingham, WA)
Refeeding an ad libitum Diet to Energy Restricted C57BL/6 Mice Restores Natural Killer Cell Numbers and Percentages during Primary Influenza Infection
Authors: Clinthorne Jonathan Frederick , Beli Eleni , Duriancik David M , Gardner Elizabeth M
Published: June 2021

We have previously shown that C57BL/6 mice fed a 40% energy‐restricted (ER) diet impairs the Natural Killer (NK) cell response to primary influenza infection. We hypothesized that refeeding ER mice with an ad libitum (AL) diet would restore the innate immune response to influenza virus. In this study three dietary groups were compared: 1) 40% ER, 2) AL fed, and 3) ER mice fed an AL diet (RF). All groups were monitored for 3 days after infection with 100 HAU of influenza A virus. Body weight and body composition were monitored over the course of the feeding (10–14 days) and after infection (3 days). RF mice exhibited a hyperphagic response, increasing body weight and body fat percentage within 5–7 days to restore to levels comparable to AL mice. Importantly, refeeding partially restored cell numbers and percentages, but not phenotypes, of NK cells in lungs, blood and spleen. In ER and RF groups, the percentages of CD27hi/Mac‐1lo (immature) NK cells were decreased in blood, but increased in spleens, compared to the AL mice. NK cells in RF and ER mice also exhibited higher expression of the activation marker B220. Lung virus titers accumulated, and remained higher, in both ER and RF animals, despite increased survival of RF mice. These data suggest that this nutritional refeeding paradigm may be necessary to increase the NK cell response to influenza infection in susceptible populations. Supported by R15AG029637 (E.M.G.)

Grant Funding Source: R15AG029637
In Vivo Modulation of Innate Immunity by Dietary Spices and Herbs
Authors: Lester Christen , DeLeon Robert , Maitin Vatsala , Vattem Dhiraj
Published: June 2021

Dietary spices and herbs are known to have immuno‐modulatory properties; however, their mechanism of action is not well understood. The effect of dietary spices and herbs on innate immunological parameters was investigated in Lumbricus terrestris. Animals fed ad libitum on Lumbricus growth medium supplemented with 0% (control), 0.1% and 0.5% (w/v) of spices and herbs. Coelomic fluid was extracted on day 2, 4 and 6. Total cell counts (TCC), viability (CV) and cell types were determined using standard microscopic methods. Nitrites/nitrates (NOx), phagocytic activity (PHAG) and respiratory burst (RB) were quantified using standard assays. qPCR was used to monitor changes in gene expression relevant to innate immunity. Among spices, turmeric and ginger treatments resulted in increased TCC (55–62%) and CV (25%). Higher NOx (20–25%) and neurophil (NP) (15–25%) counts were noted. Stoichiometric increase in RB (20–22%) and PHAG (18–20%) was observed. Among herbs, basil and oregano treatments resulted in increased TCC (35–50%) and CV (8–28%). Higher NOx (5–12%) and NP (6–10%) were noted. Stoichiometric increase in RB (22–25%) and PHAG (11–15%) was observed. Results suggest an increase in hematopoiesis and myeloid differentiation mediated by nitric oxide. Lower RB suggests increased ARE‐Nrf2 mediated antioxidant protection and fewer cytosolic assemblies of NADPH‐oxidase. Funding source: Texas State University.
Characterization of variation in inclusion of competitive‐food policy items in South Carolina school‐district wellness policies
Authors: Jones Sonya J. , Chu Yong H. , Pluto Delores M. , Frongillo Edward A.
Published: June 2021

South Carolina school districts instituted local wellness policies addressing competitive foods in response to Child Nutrition and Women, Infants and Child Reauthorization Act in 2004. Local districts vary in propensity to address the availability of competitive foods in schools, but this has not been well characterized. This study examined variation across the 85 public school districts in South Carolina through a content analysis of wellness policy documents using Robert Wood Johnson Foundation Wellness Policy Coding Tool. For each district, 28 competitive‐food policy items were coded as either present or absent. The policy items most frequently included were regulating vending machines, limiting or specifying fat or sugar content of foods or beverages, not using food for reward or punishment, limiting beverages or foods or their serving size, and regulating school stores, a la carte items, or foods sold for fundraising. The number of policy items included in a district policy ranged from 0 to 16 for primary schools and 0 to 22 for secondary schools. Cluster analysis identified five clusters of districts with similar policies based on the items, with the clusters differentiated on number of items and which items were included. These results advance understanding of variation in inclusion of policy items, but inclusion does not equate to districts' commitment to implement or effectiveness if implemented.
Perspectives and Practices related to Nutrition and Physical Activity among Home‐Based Child Care Providers
Authors: Kim Juhee , Shim Jae Eun
Published: June 2021

Objectives

To understand the obesity related practices and perceptions among home‐based childcare providers.

Method

The CRAYON (Caretaker Research Advance Youth Obesity Knowledge) group and Child Care Resource Services (CCRS) at University of Illinois at Urbana‐Champaign conducted a survey study in child care training workshops in Champaign County, IL. Total 40 home‐based care providers completed a self‐administered survey.

Results

About 78% child care providers received training on nutrition and 72% on physical activity during the past year. 95% providers taught children about nutrition and 61% provided nutrition information to parents. The important factors in deciding food menu are followed: 90% CACFP guideline or state regulation, 89% nutritional contents, 89% availability, 77% convenience, 73% children's preferences, 72% cost, and 70% parent requests. It is noted that providers consider they have about the same influence on food preferences, eating habits, and physical activity compared with those of parents. However, providers think that home environment has a stronger influence on weight status of children than child care environment.

Discussion

Not enough child care providers offer parents information on nutrition, physical activity, and obesity prevention. Further studies are needed to understand the barriers and facilitators of health promotion opportunity in home‐based child care setting.
Feeding style and toddlers' dietary intake in two agro‐ecological zones of Ghana
Authors: Kakpovbia Voke , Marquis Grace S , Colecraft Esi
Published: June 2021

In sub‐Saharan Africa, childhood malnutrition can be attributed in part to sub‐optimal feeding practices. Study objectives were to (1) examine caregivers' feeding behaviors in two agro‐ecological zones of Ghana and (2) determine the association between caregiver feeding style and child dietary intake. Events during one meal for children 1–3 y of age were observed in households in the Forest‐Savanna Transitional (n=60) and Guinea Savanna zones (n=71). A multi‐item feeding behavior instrument was used to code caregivers' actions. All served foods and all food left on the child's plate were weighed. Anthropometric measures were taken. The prevalence of stunting among all children was 21%. There was a significant difference in the median energy intake of children who refused at least one mouthful (24%) versus children who did not refuse any mouthfuls (115 vs 214 kcal, respectively; p<0.05). Caregivers in the Transitional zone were more likely to remove the child's food following a refusal than caregivers in the Guinea Savanna (p< 0.05). However, there was no significant difference in child median energy intake between zones (204 vs 173 kcal, respectively; p=0.27). Practical, hands‐on interventions are needed to help caregivers learn to respond effectively to food refusals by young children. Funded by Jim Ellis Mentorship Program and GL‐CRSP/USAID #PCE‐G‐00‐98‐00036‐00.

Grant Funding Source: US‐AID
Momordica Charantia (Bitter Melon) Inhibits Primary Human Adipocyte Differentiation by Modulating Adipogenic genes
Authors: Nerurkar Pratibha Vivek , Lee Yun Kyung , Nerurkar Vivek R.
Published: June 2021

Momordica charantia or bitter melon (BM) that is traditionally used to treat diabetes and complications has been demonstrated to alleviate hyperglycemia as well as reduce adiposity in rodents. The objective of our study was to investigate the effects of BM juice (BMJ) on lipid accumulation and adipocyte differentiation factors in primary human preadipocytes and differentiated adipocytes. Preadipocytes treated with varying concentrations of BMJ during differentiation significantly reduced lipid accumulation as well as the mRNA expression of peroxisome proliferator‐associated receptor (PPAR), sterol regulatory element‐binding protein 1c (SREBP‐1c) and resistin genes. Similarly, differentiated adipocytes treated with BMJ for 48 h demonstrated reduced lipid accumulation, perilipin mRNA expression, and increased lipolysis. Our data suggests that BM is a potent inhibitor of lipogenesis and stimulator of lipolysis activity in primary human adipocytes. BMJ may therefore prove to be an effective complementary or alternative therapy to induce anti‐obesity effects in humans. [Grants: NCCAM (R21AT003719), RCMI, NCRR (G12RRAI03061), NIH, and Hawaii Community Foundation (20041652)].
High molecular weight and high DE pectins for blood cholesterol reduction
Authors: Berger Alvin , Kolberg Lore , Franck Anne , Brouns Fred , Adam‐Perrot Aline , Zirzow Karl‐Heinz
Published: June 2021

Pectin is a texturizing/gelling agent, and a viscous soluble fiber. Effects of pectin structure on LDL‐cholesterol (LDL‐C) are unknown. In broilers fed hypercholesterolemic diets then commercial pectins for 35 d, cholesterol lowering was: citrus pectin DE70 = apple pectin DE70 > apple pectin DE35 > citrus pectin DE0 = LMW pectin = citrus pectin DE35 = cellulose (DE, degree esterification; LMW, low molecular weight), indicating high DE/potentially HMW were desirable for cholesterol lowering. In a cross‐over study with 30 mildly hypercholesterolemic persons receiving pectin or cellulose (15 g/d), in mixtures of cereal bars, fruit preparations or capsules for 3 wks, LDL‐C lowering was: citrus pectin DE70 = apple pectin DE70 (7–10% reduction vs control) > apple pectin DE35 = citrus pectin DE35 > OPF (orange pulp fiber) DE70 and LMW pectin DE70. In a trial with 30 subjects receiving 2 types of pectin (6 g/d) or cellulose in capsules for 3 wks, citrus pectin DE70 and HMW pectin DE70 similarly lowered LDL‐C 8%. High DE and HMW are important for maximizing LDL‐C lowering in pectins; source is less important.
Partially hydrogenated vegetable oils from different sources have divergent effects on lipoprotein metabolism in male F1B hamsters
Authors: Kraft Jana , Preseault Courtney , Rice Beth , Lock Adam
Published: June 2021

The objective of the present study was to examine the effects of two partially hydrogenated vegetable oils (PHVO, 50% total trans‐fatty acids) from different sources on plasma lipids, lipoproteins and lipoprotein subclass distribution in a hamster model. Thirty‐three male F1B hamsters were fed diets containing 0.12% cholesterol and 15% added fat as: 1) 15% Western diet fat (Control, CON), 2) 10% Western diet fat + 5% partially hydrogenated high‐oleic sunflower oil (PH‐SUN), and 3) 10% Western diet fat + 5% partially hydrogenated safflower oil (PH‐SAF) for 4 weeks. The addition of PHVO's to the diet increased plasma total cholesterol concentrations by 20% relative to CON (P<0.05), but only PH‐SUN increased plasma ratios of total:HDL‐cholesterol and non‐HDL:HDL‐cholesterol compared with CON (P<0.05). PH‐SUN resulted in higher concentrations of total and large VLDL relative to CON and PH‐SAF. In addition, PH‐SUN reduced the number of total LDL particles and small LDL subclass particles relative to CON and PH‐SAF (P<0.05). Long‐term consequences of the divergent effects of PHVO's on lipoprotein metabolism require further investigation.

Grant Funding Source: Dairy Australia
Increased Plasma Adiponectin and Expression of Hepatic Genes Regulating Lipid Metabolism in HPMC Fed Hamsters
Authors: Kim Hyunsook , Yokoyama Wallace , Bartley Glenn E , Young Scott A , Anderson W.H. Kerr , Hung Shao‐Ching , Albers David R , Langhorst Marsha L , Turowski Maciej
Published: June 2021

Soluble dietary fiber (hydroxypropyl‐methylcellulose, HPMC) is not absorbed by the body but its presence in the intestinal lumen increases fecal fat, sterol, and bile acid excretion which may result in reduced energy availability and indirectly changes in hepatic lipid metabolism. To elucidate the underlying this mechanisms, we measured hepatic expression of genes involved in cholesterol, bile acid, and fatty acid metabolism in male Golden Syrian hamsters fed 39% fat calorie diets containing 5% HPMC or 5% insoluble dietary fiber (microcrystalline cellulose, MCC) for four weeks. Hamsters fed HPMC gained significantly less body weight without changes in food intake and had less plasma and hepatic lipid levels than animals on MCC diet. The expression of hepatic genes related to fatty acid oxidation were up‐regulated and fatty acid synthesis were down‐regulated in hamsters fed diets supplemented with HPMC. HPMC fed animals also had higher levels of plasma adiponectin compared with control animals. Plasma adiponectin may regulate the nuclear receptors, PPAR alpha and SREBP‐1c, resulting in the up‐ or down‐regulation of the downstream genes. In addition, reduced energy availability after HPMC feeding may trigger an increase in plasma adiponectin and decrease in the expression of hepatic lipogenic genes.
Involvement of PFKFB3/iPFK2 in the suppressive effect of rosiglitazone on diet‐induced intestine inflammatory response
Authors: Li Honggui , Guo Xin , Thomas Laura , Sturino Joseph , Wu Chaodong
Published: June 2021

Overnutrition is a causal factor of metabolic syndrome. However, little attention has been paid to the regulation of overnutrition‐related intestinal inflammation as it relates to metabolic syndrome. The objective of this study is to define the role of PFKFB3/iPFK2, a master regulator of nutrient metabolism, in regulating diet‐induced intestine inflammatory response in mice. For this purpose, mice were fed a high‐fat diet (HFD) and treated with or without rosiglitazone, an insulin‐sensitizer that also has an anti‐inflammatory effect. Compared to wild‐type littermates, mice that lack one allele of PFKFB3 (PFKFB3+/− mice) displayed a significant increase in the expression of intestinal inflammatory markers such as toll‐like receptor 4 and proinflammatory cytokines on a HFD. These data indicate that disruption of PFKFB3 exacerbates diet‐induced intestine inflammatory response. When treated with rosiglitazone, the expression of the above inflammatory markers was markedly decreased in HFD‐fed wild‐type mice, and, to a lesser extent, in HFD‐fed PFKFB3+/− mice. Additionally, treatment with rosiglitazone normalized systemic insulin sensitivity and glucose homeostasis in HFD‐fed wild‐type mice, but not in HFD‐fed PFKFB3+/− mice. Therefore, PFKFB3/iPFK2 is involved in the suppressive effect of rosiglitazone on diet‐induced intestine inflammatory response.
Vitamin D supplementation reduces C‐reactive protein and insulin resistance in women with type 2 diabetes mellitus
Authors: Flores Mario , Barquera Simon , Macias Nayeli , Salmeron Jorge , Greenberg Andrew , Wood Richard , Long Kurt , Meydani Simin
Published: June 2021

A randomized, double blind, placebo‐controlled clinical trial was conducted to evaluate the effect of vitamin D supplementation on C‐reactive protein (CRP) and insulin resistance in 104 postmenopausal women with type 2 diabetes mellitus. Participants received a vitamin D capsule –cholecalciferol 4,000 IU‐ (n=52) or placebo (n=52), daily during 6 mo. The study was approved by the Ethics committee at NIPH. All participants signed an informed consent.

Results

Median CRP concentration was 5.0 mg/L (ir: 1.0, 8.5). HOMA index at baseline was 7.13 ± 3.8. Serum 25‐OH‐D at baseline was 54.5 ± 15.7 nmol/L. 93% of patients had 25‐OH‐D levels <80 nmol/L, and 40% <50 nmol/L. Experimental groups were similar on most variables at baseline. After 6 months, there was an increase in serum 25‐OH‐D of 25 ± 2.6 nmol/L in the supplemented group, and an increase of 0.8 ± 2.2 nmol/L in the placebo group (p<0.001). There was a 64% reduction on CRP among supplemented women who had baseline CRP concentrations >5.0 mg/L (p<0.05). A 24% reduction in HOMA‐IR after 6 months was observed among supplemented women who had a baseline HOMA >6.0 (p=0.06).

Conclusion

Vitamin D supplementation during 6 months reduced CRP levels and insulin resistance among diabetic, postmenopausal women with high HOMA index and elevated CRP levels.

Supported by Ellison Medical/INF, Boston.
Blueberry diet protect against atherosclerosis in apoE‐deficient mice by inhibiting scavenger receptor expression
Authors: Xie Cheng‐Hui , Wu Xianli , Nagarajan Shanmugam
Published: June 2021

Atherosclerosis is an inflammatory process that leads to the onset of cardiovascular disease. Recently we reported that apoE knockout (apoE−/−) mice fed AIN‐93G diet (control) formulated to contain 1% freeze‐dried whole wild blueberries (BB) were found to have significantly less oil red O positive fatty streak atherosclerotic lesions in aorta. The scavenger receptor‐mediated uptake of oxidized‐LDL (oxLDL) by macrophages leads to foam cell formation, which is an initial event in the formation of atherosclerotic fatty streak lesions. We hypothesize that the atheroprotective effect of BB is mediated by inhibition of scavenger receptor expression. The mechanism contributing to the atheroprotective effects of blueberry‐supplemented diet was addressed in apoE−/− mice. Reduced mRNA expression of scavenger receptors (CD36, scavenger receptor A and CD68) in proximal aorta was found in BB fed group compared to control diet‐fed mice. Further, protein levels of scavenger receptors in aorta as well as macrophages were also reduced in mice fed BB diet compared with control diet. These findings suggest that the atheroprotective effect of the BB supplemented diet is mediated in part by inhibiting scavenger receptor expression that could result in reduced oxLDL uptake leading to fatty streak lesions, an early event of atherogenesis. USDA‐CRIS‐6251‐5100002‐06S.