bluuebunny/crossref_metadata_2025 huggingface dataset:
Absorption of catechin auto‐oxidation dimers by confluent Caco‐2 cell monolayers
Authors: Neilson Andrew Peter , Green Rodney J , Peters Catrina M , Cooper Bruce R , Bomser Joshua A , Ferruzzi Mario G
Published: June 2021

Formation of homo‐ and hetero‐dimers through auto‐oxidation of epigallocatechin gallate (EGCG) and epigallocatechin (EGC) under simulated digestion has been reported. However, little data exists regarding potential absorption of these dimers. The objective of this study was to first demonstrate intestinal absorption of these dimers in vitro in order to characterize their potential relevance in vivo. Dimers generated by pH‐induced (pH 7.0) auto‐oxidation of catechin reactants (0.3 mM) in saline were incubated on highly differentiated Caco‐2 cell monolayers for 3 h. HPLC analysis of cell extracts with electrochemical array detection and MS/MS characterization indicated the presence of the EGCG homodimers theasinensin (m/z 913) and P‐2 (m/z 883) as well as Phase‐II conjugated metabolites of EGC homodimers (m/z 689 and 593) in the cells. These results indicate that catechin auto‐oxidation dimers formed through food processing or potentially through digestive reactions may be absorbed by human intestinal epithelial cells. Furthermore, catechin dimers appear to be substrates for the Phase‐II detoxification pathways known to metabolize monomeric catechins. These observations suggest that the potential digestive formation and subsequent absorption of catechin auto‐oxidation dimers in vivo warrants further investigation. (Supported by NIH grant CA119210‐01A1).
High prevalence of low serum 25‐OH vitamin D concentrations in women of child‐bearing age in Jordan during summer
Authors: Gharaibeh Muna A. , Stoecker Barbara J.
Published: June 2021

Serum 25‐(OH) Vitamin D [25(OH)D] was assessed in 93 women of child bearing age in Jordan in July 2007. Mean age (SD) was 34.0 (6.0) and body mass index (BMI) was 29.6 (15.2) with 77% of women having BMI ≥ 25 kg/m2. Mean concentration of 25(OH)D was 25.6 (9.6) nmol/L. Only two women (2.2%) had 25(OH)D concentrations less than 12.5 nmol/L but 71 (76.3%) of the women had values between 12.5 and 30 nmol/L. Twenty‐one percent of the women had 25(OH)D concentrations between 30 and 75 nmol/L but no women had values above 75 nmol/L. In this sample, 86% of the women wore clothing that exposed only their face and hands, but dress style had no significant effect on 25(OH)D concentrations. The women reported a mean of 5.3 (4.6) hours of sun exposure per week. Tendency to avoid sun exposure varied between women: 13.9% (n=13) reported they always avoided sun exposure and 69.9% (n=65) never avoided the sun but reported sunlight exposure was not significantly correlated with 25(OH)D. Liver consumption varied among women: 43% (n=40) never or rarely consumed liver. Milk consumption was low and most of the milk consumed in Jordan is not fortified with vitamin D. Only 7 women reported taking multivitamin supplements that might include vitamin D, and 82.8% of women did not take any type of supplementation. Despite the abundant sunlight in Jordan during summer, vitamin D inadequacy was highly prevalent in women of child‐bearing age. (Supported by Oklahoma State University, Stillwater, OK)
Activation of T lymphocytes by polysaccharide‐protein complex from a Chinese medicinal nutrient, Lycium barbarum L
Authors: Chen Zhisong , Tan Kwong Huat , Tay Samuel SW , Chan Soh Ha
Published: June 2021

Lycium barbarum fruit, also known as wolfberry, is a Chinese medicinal nutrient containing many micronutrients and phytochemicals, such as essential vitamins, beta‐carotene, zeaxanthin, and polysaccharides. We report that polysaccharide‐protein complex from Lycium barbarum L (LBP) enhances immunity by activating T lymphocytes. Crude LBP was isolated from Lycium fruit and purified to five homogenous fractions, designated as LBPF1, LBPF2, LBPF3, LBPF4, and LBPF5. We found that LBP significantly stimulated mouse splenocyte proliferation. The active fractions were LBPF4 and LBPF5. The proliferation proved to be of T cells, but not B cells. Crude LBP, LBPF4, and LBPF5 markedly enhanced CD25 expression, activated transcription factor NFAT and AP‐1, and induced IL‐2 and IFN‐¦Ã gene transcription and protein secretion. LBP significantly induced T cell proliferation by i.p. and p.o. administration. Both in vitro and in vitro data indicate that LBP is capable of activating T cells. We conclude that activation of T lymphocytes by LBP may contribute to its immuno‐enhancement function.

This work was supported by funds from the WHO Collaborating Centre for Research and Training in Immunology, National University of Singapore (R‐188‐000‐001‐731).
Targeted removal of the selenocysteine tRNA gene (trsp) in epidermis modulates skin function and development.
Authors: Sengupta Aniruddha , Lichti Ulrike F , Carlson Bradley A , Yuspa Stuart H , Hatfield Dolph L
Published: June 2021

Selenium is an essential dietary micronutrient having numerous health benefits. It is incorporated into proteins (selenoproteins) as selenocysteine (Sec). Selenoprotein synthesis depends on Sec tRNA, a unique eukaryotic tRNA that governs the expression of only a single class of proteins, the selenoproteins. Manipulating Sec tRNA structure and expression can selectively alter selenoprotein synthesis. To understand the importance of selenoprotein expression in skin development and function, we targeted the removal of the Sec tRNA gene (trsp) in mouse epidermis, using mammalian K14 promoter based loxP‐Cre technology. Our results show that the knockout mice (Δtrsp) have stunted growth and a shorter life span as compared to control mice. They have flaky and wrinkled skin and histological analysis revealed moderate epidermal hyperplasia along with coagulative necrosis of the epidermis. The knockout mice have sparse hair and histological examination suggested that hair morphogenesis might be affected. Real‐time PCR analysis of skin of knockout and control mice shows a decrease in the expression of selenoprotein mRNAs in knockout mice, with the decrease being most significant in epidermis. These studies report a novel and previously unidentified role of selenoproteins in skin function and development. This research was supported by the Intramural Research Program of the NIH, NCI, CCR.
Vitamin C depletion in healthy adults is associated with impaired mood states and increased perception of fatigue during sub‐maximal walking
Authors: Appel Christy L , Johnston Carol S , Huck Corey J , Beezhold Bonnie L , Swan Pamela D
Published: June 2021

Vitamin C (VC) status can impact the synthesis of neurotransmitters and carnitine, a molecule required for energy production from fatty acids. Hence, we examined whether VC depletion was associated with impaired mood states and with perceptions of fatigue during moderate exercise using the Profile of Mood States questionnaire and Borgâs RPE 6â20 scale respectively. In a cross‐sectional study of 78 healthy adults (age=31.0Â±7.7, BMI=23.6Â±3.7), men with low VC status (n=15, plasma VC â¤ 0.6 mg/dl) had higher tension (+41%, p=0.017) and total mood disturbance (+290%, p=0.013) scores than men with adequate VC status (n=22). In a randomized, placebo‐controlled trial, obese adults followed a calorie‐restricted diet and consumed either placebo (n=10) or 500 mg VC (n=10) capsules daily. After 4 weeks of diet adherence, both groups lost ~4 kg, but plasma VC concentrations (0.63Â±0.21 and 1.10Â±0.14 mg/dl, p<0.001) and depression scores (4.9Â±4.0 and 1.9Â±2.1, p=0.050) differed for the placebo and VC groups. At week 4, RPE during sub‐maximal walking (mean at 40‐, 50‐, and 60‐min) differed by group (13.23Â±0.95 and 12.26Â±0.66, p=0.043 for placebo and VC respectively). These data suggest that VC status is associated with impaired mood states as well as perceptions of fatigue during exercise in lean and obese adults. This research was supported in part by the General Mills, Bell Institute of Health and Nutrition.
Trends in vitamin D intake between 1980 and 2002 among adults in the Minneapolis St Paul, MN metropolitan area
Authors: Harnack Lisa J , Steffen Lyn , Zhou Xia , Luepker Russell
Published: June 2021

Trends in dietary vitamin D intake from 1980–82 to 2000–02 were examined using data collected from the Minnesota Heart Survey, a surveillance study of trends in risk factors for cardiovascular disease among probability samples of adults in the Minneapolis‐St Paul, MN metropolitan area. Surveys were conducted in 1980–82, 1985–87, 1990–92, 1995–97, and 2000–02. Twenty‐four hour recalls were collected to assess dietary intake, with most data collection procedures employed consistently across survey periods. Results indicate that vitamin D intake from dietary sources decreased between 1980–82 and 2000–02. Among men age‐adjusted mean vitamin D intake decreased from 7.3 mcg/day in 1980–82 to 6.0 mcg/day in 2000–02 (p <0.001). Among women vitamin D intake decreased from 4.8 mcg/day to 4.5 mcg/day over the same time period (p=0.004). These trends were generally consistent across age, education level, race, and body mass index strata. It is possible that declines in vitamin D intake from dietary sources have been offset by increased use of dietary supplements containing vitamin D. However, we were unable to fully explore this possibility due to the limited information available in our survey regarding dietary supplement use. In summary, results suggest that the vitamin D content of the diet has been on the decline over the past twenty years, potentially contributing to the resurfacing of vitamin D deficiency in the U.S.
Comparison of self‐reported and measured dietary supplement use: preliminary results from the SURE Study
Authors: Murphy Suzanne P. , Wilkens Lynne , Monroe Kristine , Albright Cheryl , Yonemori Kim , Morimoto Yukiko , Steffen Alana
Published: June 2021

Use of dietary supplements is common in the US, but the accuracy of reporting dietary supplement intake has not been evaluated in detail, in part because there is not a reference method of comparison. The Supplement Reporting (SURE) Study has addressed this concern by measuring supplement use using a unique inventory method. Interviewers visited the participants’ homes five times across one year to count the pills and tablets in all dietary supplement containers. Participants are a subset of the Multiethnic Cohort in Hawaii and Los Angeles who reported regular use of at least one dietary supplement. We present here a comparison of self‐reported supplement use for the past month (from a daily diary) with the results of a 3‐month inventory for 185 participants who completed the first year of the study. Across 19 types of supplements (3 multivitamins, 11 single nutrients, and 5 herbal supplements), the mean number of pills taken per day was similar for the two methods, but consistently slightly higher for the diary method. Spearman's correlation coefficients ranged from 0.38 for zinc to 0.88 for saw palmetto. Most (84%) of the correlations were greater than 0.60. Future analyses will extend these comparisons to include the full sample (n = 402) and to examine other methods of reporting supplement use (recalls and a frequency questionnaire). Supported by NCI grant # R01 CA106744.
Event tracking model of adhesion identifies load‐bearing bonds in leukocyte rolling at low shear
Authors: Pospieszalska Maria K. , Zarbock Alexander , Pickard John E. , Ley Klaus
Published: June 2021

P‐selectin binding to PSGL‐1 mediates leukocyte rolling under conditions of inflammation and injury. Here, we develop a three‐dimensional, direct, stochastic π‐calculus‐driven Event Tracking Model of Adhesion (ETMA) to capture the dynamics of and make predictions about P‐selectin—PSGL‐1 bonds under low shear stress conditions. Instantaneous displacements, translational and rotational velocities, leukocyte‐endothelium distances, and number, location and lifetime of total and load‐bearing bonds are derived from measured physiological and biophysical parameters of leukocyte rolling and molecular bond properties. The model explains the commonly observed “stop‐start” type rolling behavior, and reveals that a few load‐bearing bonds are sufficient to support rolling while overall a large number of bonds dissociate before becoming load‐bearing. The model provides high resolution data corresponding well with experimental results obtained by our own and other groups. ETMA is the first model that reconstructs the exact sequence of bond formation and dissociation events in the rolling process and is uniquely able to identify the behavior of load‐bearing bonds. This work was supported in part by the NIH (grant 2R01EB002185) and Deutsche Forschungsgemeinschaft (grant AZ 428/2‐1).
Neuropathic Pain Mechanisms: A Role for Chemokines
Authors: White Fletcher A.
Published: June 2021

Chronic (neuropathic) pain is one of the most widespread and intractable of human complaints, as well as being one of the most difficult syndromes to treat successfully with drugs or surgery. The development of new therapeutic approaches to the treatment of painful neuropathies requires a better understanding of the mechanisms that underlie the development of these chronic pain syndromes. As inflammatory processes often accompany the development of neuropathic pain, I will discuss the role that chemokines might play in integrating the development of pain and inflammation. Importantly, chemokines in DRG neurons seem to act as upregulatable neurotransmitters that produce excitatory effects in the DRG and spinal cord through a variety of mechanisms. The ability of small molecule antagonists of CCR2 and CXCR4 receptors to ameliorate ongoing pain hypersensitivity in animal models clearly indicates the importance of chemokine signaling in this behavior. Taken together, targeting the chemokine system may provide a novel form of therapeutic intervention into states of chronic pain.
PHLiPPing the Switch in Lipid Second Messenger Signaling
Authors: Newton Alexandra C
Published: June 2021

The lipid second messenger‐activated kinases protein kinase C (PKC) and Akt control cell growth, proliferation, and survival. PKC transduces signals that result in diacylglycerol production following, typically, phospholipase C activation; Akt transduces signals that result in generation of 3’‐phosphoinositides catalyzed by PI 3 kinase. Both pathways acutely control the exquisite balance between cell survival and apoptosis. Signaling by these kinases is propagated by two mechanisms: a phosphorylation cascade triggered by the upstream kinase PDK‐1, and binding of the relevant lipid second messenger. Similarly, signaling is terminated by two mechanisms: removal of the activating lipid second messenger and dephosphorylation of the kinase. We have recently identified a novel phosphatase family, PHLPP (for PH domain leucine‐rich repeat protein phosphatase) that directly dephosphorylates Akt and PKC, terminating signaling by these two kinases. In the case of the diacylglycerol pathway, PHLPP controls the amplitude of signaling by controlling the amount of protein kinase C in the cell. In the case of the PI3 kinase pathway, PHLPP controls the amplitude of signaling by controlling the degree of agonist‐evoked phosphorylation of Akt. Thus, the protein phosphatase PHLPP plays a central role in lipid second messenger signaling by directly opposing the function of the protein kinase PDK‐1.
Mechanisms for Maintaining Genome Stability at the Replication Fork
Authors: Cimprich Karlene A. , McDougall Christina , Lin Jia‐Ren
Published: June 2021

Maintenance of genome stability is of critical importance to the cell, and the integrity of the genome can be threatened when DNA is damaged by either endogenous or environmental agents. DNA is particularly susceptible to damage during DNA replication, when replication forks can stall at DNA lesions. As a result, the cell has finely tuned processes to accurately replicate DNA, to repair damaged DNA, and to stabilize/restart stalled replication forks. A failure to carry out these processes can lead to the loss of genomic integrity by interfering with proper repair of DNA, and by leading to the collapse of stalled forks into double‐strand breaks. The DNA damage checkpoint helps to maintain genomic stability when replication forks arrest by stabilizing the stalled forks, inducing cell cycle arrest, and coordinating different repair processes with each other. Key effectors of this checkpoint are two kinases, ATR (ATM and Rad3‐related) and its downstream effector Chk1. The ATR pathway displays remarkable flexibility in terms of the types of lesions that it can detect, a property that is critical to its function. Recent work in our lab has focused on understanding how the stalled fork is detected, stabilized and processed. Here, we will describe our work on the mechanisms leading to ATR activation by stalled forks. In addition, we will discuss new studies focused on identifying novel effectors of replication fork stability.
Metabolic syndrome risk in young adults is associated with dietary and lifestyle factors
Authors: Morrell Jesse Stabile , Burke Joanne Delaney , Lofgren Ingrid Elizabeth , Reilly Ruth Anne
Published: June 2021

Metabolic syndrome (MbS) risk factors were examined in 1,396 18–24 year old college adults (72% women) as a part of the Young Adult Health Risk Screening Initiative, an ongoing cross‐sectional investigation at the University of New Hampshire. From July 2005–Aug 2007, 31% of men and 16% of women were found to have ≥ 2 MbS risk factors. The number of MbS risk factors was higher among participants who had a BMI > 25 (vs. BMI 18.5–24.9, p < 0.001); lived in off‐campus apartments (vs. college dorms, p < 0.05); were non‐health majors (vs. nutrition majors, p < 0.02); were physically inactive (vs. physically active > 90 minutes/day, p = 0.06); skipped ≥ 4 meals per week (vs. non meal‐skippers, p < 0.01); ate at restaurants ≥ 3 times per week (vs. non restaurant patrons, p < 0.01); and took a multivitamin/mineral supplement (vs. no supplement, p < 0.01). Three day dietary analysis (Diet Analysis+ Plus 7.0/8.0) were used to examine nutrient intake differences. As compared to participants with no MbS risk factors, participants with ≥ 2 MbS risk factors had higher intakes of total fat (72.3 vs. 69.4 g, p < 0.05), saturated fat (24.2 vs. 22.6 g, p < 0.01), omega‐6/omega‐3 fatty acid ratios (12.5 vs. 11.2, p < 0.05); and lower intakes of ethanol (4.6 vs. 8.0 g, p < 0.05), fiber (18.7 vs. 20.0 g, p = 0.06) and magnesium (254.0 vs. 272.2 mg, p < 0.02). Findings suggest dietary and lifestyle factors are associated with MbS risk in young, college‐aged adults.
Both low and high fat diets inconsistently induce obesity in C57BL/6J mice and obesity compromises adipose n‐3 fatty acid and zinc status
Authors: Taylor Carla Gwen , Tallman Diana , Noto Amy
Published: June 2021

The purpose of this study was to determine whether the inconsistency in development of diet induced obesity (DIO) in C57BL/6J mice is related to dietary fat level, or metabolic derangements associated with high weight gain, including variations in adipose tissue fatty acid composition and zinc status. C57BL/6J mice were randomized to either the low fat (LF; 7% soybean oil w/w, 16% kcal from fat) or high fat (HF; 9% soybean oil + 21% lard w/w, 55% kcal from fat) diet for 16 weeks. The diets were also controlled for zinc content. Mice were dichotomized by median weight into high (HBW) and low body weight (LBW) groups. The novel findings were that (i) even a LF diet produced obesity as HBW and LBW groups contained mice fed both HF and LF diets, (ii) adipose phospholipid n‐3 fatty acids were lower in HBW mice, despite diet composition, and (iii) HBW mice had lower concentrations of zinc in adipose and pancreatic tissue. These results suggest that DIO in C57BL/6J mice is not entirely dependent on a HF diet and that obesity, regardless of diet, results in an unfavourable adipose phospholipid n‐3 fatty acid and zinc status. [Supported by the Natural Sciences and Engineering Research Council (NSERC) and University of Manitoba Research Development Fund.]
Programming Body Composition in Offspring by Maternl Obesity: Adipogenesis and wnt/β‐catenin signaling
Authors: Shankar Kartik , Harrell Amanda , Ronis Martin J , Badger Thomas M
Published: June 2021

Maternal obesity during pregnancy significantly influences the risk of offspring obesity. We recently demonstrated that maternal obesity at conception programs obesity in the offspring. Obese dam offspring when weaned on high‐fat diets gain significantly greater body weight/adiposity and develop insulin resistance than lean dam offspring. Histomorphometry revealed greater adipose hypertrophy in offspring of obese dams. To examine the underlying mechanisms, we examined wnt/β‐catenin signaling, a critical negative regulator of adipogenesis. Analyses of 85 genes involved in Wnt/β‐catenin signaling revealed significant induction of wnt signaling antagonists, Sfrp2, 4, dickkopf 1 and wif1 specifically in the adipose tissue of offspring of obese dams. Conversely, lean dam offspring showed significant reduction in Sfrp5. Cellular phospho‐GSK3β and nuclear β‐catenin levels in adipose tissue were significantly lower in obese offspring compared to their lean counterparts. In addition protein levels of adipogenic factors PPAR‐γ and C/EBP‐α were significantly increased in offspring of obese dams. Our data suggest that maternal obesity at conception leads to programming of the Wnt/β‐catenin pathway in the offspring which may contribute to greater adipogenesis and obesity later in life. Support ARS‐CRIS6251‐51000‐005‐00D.
Developing a mechanism to measure the absorption of bacterially‐synthesized folate across the colon: Testing of caplets with a pH‐sensitive coating designed for colon targeting
Authors: Aimone Ashley , Connolly Bairbre , Chaudhary Surinder , Lugtu Jamie , Martinuzzi Frank , O'Connor Deborah L
Published: June 2021

We hypothesize that bacterially synthesized folate in the large intestine may significantly influence the folate status of humans and, specifically, colonocytes. Research in this area has been limited due to the absence of a non‐invasive means to quantitatively deliver test doses of folate to the colon. The purpose of this study was to design and test the effectiveness of two pH‐dependent coatings in delivering intact placebo caplets to the large intestine. Barium sulphate caplet cores (19.1 x 9.7mm) were coated with Eudragit® L100 and S100, in either a 1:0 or 3:1 ratio. Each formulation was administered to ten healthy volunteers, and monitored in‐vivo via serial abdominal fluoroscopic images. Test caplets with 3:1 coating formulations had 40% higher colon‐targeting specificity compared to 1:0 caplets, and tended to begin dissolving at a later time after administration (p=0.09). The total time from administration to complete dissolution was also significantly longer for 3:1 coated caplets (p=0.003). These results suggest that barium sulphate caplets with a 3:1 (Eudragit L100:S100) coating formulation ratio would be a suitable delivery system for investigating the absorption of folate across the large intestine.

Sponsored by NSERC and the CIHR Training Program in Clinical Research.
Dietary intake of fat in urban Guatemalan schoolchildren
Authors: Toher Claire , Montenegro‐Bethancourt Gabriela , Vossenaar Marieke , Mathias Paul M. , Solomons Noel W. , Bermudez Odilia I.
Published: June 2021

Background:

Altered food habits in nutritional transition have implications for health and disease patterns that start in childhood.

Objectives:

To evaluate the total fat (TF) and fatty acid (FA) intake among 3rd and 4th grade schoolchildren in Quetzaltenango, Guatemala.

Methods:

We studied 449 children of both sexes, 230 in private and 219 in public schools. Intake estimation comprised a single 24‐h pictorial self‐recording, supplemented by a dietitian interview to quantify amounts. TF and FA intakes were calculated using the USDA as well as INCAP food databases, and compared with their 2003 WHO recommended nutrient intakes (RNI), expressed as a percentage of total energy.

Results:

The median intake of TF (29%), saturated fat (SF) (10%), total PUFA (6%) and omega‐6 FA (6%) for all children were within WHO guidelines, whereas that for omega‐3 FA (ω‐3) (0.5%) was below the 1.0–2.0% RNI. Intakes of SF (p<0.01) and total ω‐3 (p<0.05) were significantly higher in the private school sample. Median TF consumption was 8.3 g higher when calculated using the USDA database, as compared to the INCAP table.

Conclusion:

With the exception of ω‐3, current TF and FA intakes are acceptable in the study population, although long‐term monitoring would be prudent.
Early B‐cells recruitment and activation of NF‐κB in adipose tissue are early features of postprandial vascular endothelial dysfunction
Authors: Magné Joëlle , Fischer Romy , Mariotti François , Mathé Véronique , Giraudet Flore , Tomé Daniel , Huneau Jean‐François
Published: June 2021

In the postprandial state, a low‐grade inflammatory response may contribute to the adverse effects of high‐saturated fat /high‐sucrose meals on vascular endothelial function, a hallmark of early atherogenesis. In the present study we investigated whether a high‐fat load (HFL), a model of postprandial vascular dysfunction in the rat, induces very early (1) the expression of endothelial adhesion markers on blood leukocytes and (2) the nuclear translocation of NF‐κB, a key transcription factor in the inflammatory cascade. The expression of CD11B, CD62L and CD45RA on blood leukocytes was determined by flow cytometry in 10 healthy rats before and 2 hours after a HFL or a water load (WL). Rats were killed 2h after the load, and visceral adipose tissue was sampled.

The neutrophil count markedly increased 2h after the HFL, while remaining steady after the WL. The HFL decreased B‐cell count and expression of the activation marker CD62L. In nuclear extracts of adipose tissue, an increase of activated NF‐κB was observed after the HFL.

As far as we know, this is the first study evidencing an acute, postprandial (1) meal‐specific decrease in blood B‐cells and (2) activation of the NF‐κB pathway in adipose tissue. Because they happen very early after the meal, these pro‐inflammatory features probably play a central triggering role in the activation of the complex postprandial proatherogenic phenotype.
Implication of new WHO growth standards on estimated prevalence and identification of early risk factors for malnutrition in rural Malawian infants
Authors: Prost Marc Andre , Jahn Andreas , Floyd Sian , Mvula Hazzie , Mwaiyeghele Eleneus , Mwinuka Venance , Mhango Thomas , Crampin Amelia C , McGrath Nuala , Fine Paul E. M. , Glynn Judith R.
Published: June 2021

We assessed how switching from NCHS to new WHO child growth standards affects estimated prevalence of wasting, underweight and stunting, and the identification of risk factors. Malawian children (n=1328) were visited at 0–4 months and 11–15 months. Demographic, socio‐economic, health history, anthropometry, maternal nutritional status and feeding practices variables were collected. Weight‐for‐length, weight‐for‐age and length‐for‐age were calculated using both references. In early infancy, prevalence estimates were 2.9, 6.1, and 8.5 folds higher for stunting, underweight and wasting respectively using WHO standards compared to the NCHS reference (p<0.001 for all). At one year wasting and stunting did not differ significantly according to reference used but prevalence of underweight was half that with the NCHS reference (p<0.001). Patterns of risk factors for malnutrition at one year were similar between growth references for all outcomes. Results suggest differences in prevalence estimates depend on population's nutritional status and should not be assumed from previous findings. Adopting the new standards will have implications for feeding programs targeting lactating mothers. Risk factors identified with WHO standards remain comparable to those previously found with NCHS reference in similar settings.

This work was supported by the Wellcome Trust.
Flavonoid intake and risk of pancreatic cancer in male smokers (Finland)
Authors: Bobe Gerd , Weinstein Stephanie J. , Albanes Demetrius , Hirvonen Tero , Ashby Jason , Taylor Phil R. , Virtamo Jarmo , Stolzenberg Rachael Z.
Published: June 2021

We examined the association between flavonoid consumption and development of pancreatic cancer within the ATBC Cancer Prevention Study cohort. Of the 27,111 healthy male smokers (50–69 years) who completed a self‐administered dietary questionnaire at baseline, 327 developed exocrine pancreatic cancer during follow‐up (1985–2003; median 15.1 years). Intakes of total flavonoids, 3 flavonoid subgroups, and 7 individual flavonoids were estimated from a validated food frequency questionnaire. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. Overall, flavonoid intake was not significantly associated with pancreatic cancer. However, in stratified analysis, greater total flavonoid intake was associated with decreased pancreatic cancer risk in participants randomized during the trial to placebo (4th vs. 1st quartile, HR = 0.45, 95% CI 0.23, 0.92; p‐trend = 0.02) and not to supplemental α‐tocopherol (50 mg/d) and/or β‐carotene (20 mg/d; p–interaction = 0.008). Similar patterns and significant interactions were observed for flavonols, flavan‐3‐ols, kaempferol, quercetin, catechin, and epicatechin. Our data suggest that a flavonoid‐rich diet may decrease pancreatic cancer risk in male smokers not consuming supplemental α‐tocopherol and/or β‐carotene. This research was supported in part by the Intramural Research Program of the NIH and NCI.
ATF4 binding to a C/EBP‐ATF composite site is not sufficient to induce endogeneous human System A transporter 2 (SNAT2) transcriptional activation during endoplasmic reticulum stress
Authors: Gjymishka Altin , Kilberg Michael S.
Published: June 2021

Activation of the amino acid response (AAR) and unfolded protein response (UPR) pathways converge at the phosphorylation of eIF2α, which leads to synthesis of the transcription factor ATF4. The System A amino acid transporter SNAT2 gene contains a C/EBP‐ATF composite site that binds ATF4 and triggers increased transcription during the AAR. Despite increased ATF4 synthesis during the UPR, SNAT2 transcription is not enhanced. This observation leads to the question, is ATF4 binding to the SNAT2 C/EBP‐ATF site sufficient to induce SNAT2 gene transcription? Chromatin immunoprecipitation (ChIP) illustrated that SNAT2 transcription is not induced following UPR activation, despite increased binding of ATF4 to the SNAT2 C/EBP‐ATF site. ChIP analysis also showed that recruitment the general transcription factors to the SNAT2 promoter and hyperacetylation of histone H3 occurs only in response to activation of the AAR but not the UPR. In contrast, the UPR pathway provoked enhanced SNAT2 transcription from a plasmid‐based luciferase reporter driven by a SNAT2 fragment containing the C/EBP‐ATF composite sequence and mutation of the sequence abolished the induction. The results demonstrate that ATF4 binding alone is not sufficient to illicit enhanced transcription and that parallel changes in chromatin structure are necessary as well. Funded by grants from the NIH (DK‐52064, DK‐70647).
Induction of apoptosis by SAMC, a biotransformed garlic derivative, through caspase protein activation on human gastric cancer cells
Authors: Lee Yongkyu
Published: June 2021

Epidemiological and experimental carcinogenesis studies show evidence that components of garlic have anticancer activity. Most of allyl sulfides of garlic, which are absorbed in gastrointestinal tract, were also reported to biotransform to the corresponding allylmercapto glutathione S‐congugate after reacting with endogenous antioxidants, such as cysteine and reduced glutathione(GSH). One of these allylmercapto glutathione S‐congugate, SAMC(S‐allylmercapto‐L‐cysteine), was reported that showed inhibitory effect on tumorigenesis, but the mechanisms of which are poorly understood. In the present study, we investigated the effect of SAMC on the growth of human gastric cancer SNU‐1 cells. Upon treatment with SAMC, a concentration‐dependent inhibition of cell proliferation was observed and cells developed many of the hall mark features of apoptosis, including DNA fragmentation and an increase in the sub‐diploid population. Also we investigated the effect of SAMC on the mitochondria release of cytochrome c, which is known that enters the cytosol and forms a complex with Apaf‐1 and a pro‐form of caspase‐9, then induces the activation of other signaling proteins. The anti‐proliferative and apoptotic effect of SAMC was associated with an induction of Bax, p53, and caspase‐9, rather than an induction of Bcl‐2 and p21. Mitochondrial cytochrome c activation and an in vitro caspase‐3 activity assay demonstrated that the activation of caspases accompanies the apoptotic effect of SAMC, which mediates cell death. These results suggest that the apoptotic effect of SAMC on gastric cancer SNU‐1 cells may converge caspase‐3 activation through the induction of Bax and p53, rather then Bcl‐2 and p21.
Increasing age lowers whereas being Mexican American increases overall diet quality in children
Authors: Kranz Sibylle , Findeis Jill
Published: June 2021

The Revised Children's Diet Quality Index (RC‐DQI) was used to determine overall diet quality in a nationally representative sample of 2–5 year olds (n=1,521; NHANES 1999–2002). Self‐reported socio‐demographic and activity data was used in linear regression models examining the effect of age, gender, ethnic group, income (poverty income ratio (PIR)), and other variables on RC‐DQI scores. Models for the full sample and stratified by income‐eligibility for the WIC (PIR<1.85, N=861) and Food Stamp Program (FS, PIR<1.3, N=676) were developed. Analysis was conducted using survey routines in STATA 9.2. Increasing age was associated with lower and being Mexican American with higher RC‐DQI score (referent: Non‐Hispanic white). In the full sample, increased PIR was associated with better diet quality (^‐coefficient 1.22, p‐value<0.001). Boys had better diet quality than girls (^‐coefficient 1.87, p‐value<0.04) the WIC‐eligible group. Food program participation indicated trends to better diet quality but was not statistically significant. Interventions to improve diet quality should target young children, especially in low‐income families. Future analysis of diet quality should focus on differences in food groups and nutrients consumed by Mexican American children compared to other ethnic groups.

Support from USDA RIDGE Grant #K981834‐21 and a College of Health and Human Development seed grant.
Defining Cardiac Cell Populations and Their Interactions
Authors: Baudino Troy A , Banerjee Indroneal , Intwala Arti
Published: June 2021

Cardiac fibroblasts, myocytes, endothelial cells and vascular smooth muscle cells are the major cellular constituents of the heart. Our recent studies have allowed us to observe alterations in the myocardial cell populations during development, in the adult animal and during disease using both surgical and genetic models. Whole hearts were isolated from mice during the neonatal and adult stages and single cell suspensions were prepared. Heterogeneous cell populations were immunolabeled for specific cell types and examined using Fluorescence Activated Cell Sorting (FACS) analyses. In addition, the left ventricle, right ventricle and septa were isolated, fixed and sectioned for morphometric analyses. These same cardiac regions were analyzed using FACS analyses. We observed that the adult murine myocardium is composed of approximately 56% myocytes, 27% fibroblasts, 7% endothelial cells and 10% vascular smooth muscle cells. Moreover, our morphometric and FACS data demonstrated similar percentages in both analyses. Furthermore, our current studies have demonstrated dramatic cardiac cell population shifts in IL‐6‐ and periostin‐deficient mice, as well as in a pressure overload hypertrophy model. Taken together, these data have enabled us to establish a homeostatic model for the myocardium that can be compared to other genetic and cardiac disease models.
What Pathologists Look For To Determine If Lymph Nodes Contain Cancer
Authors: Weidner Noel
Published: June 2021

Cancers spread via lymph nodes, especially carcinoma and lymphoma. Carcinomas spread from their primary sites of origin to regional lymph nodes via lymphatics after carcinoma cells invade lymphatics. The metastatic cells first involve the regional sentinel lymph nodes followed by other nodes, eventually entering the thoracic duct and systemic vasculature. Tumor appears first seen in subcapsular and peri‐sinusoid spaces, but the entire node may be replaced by metastatic carcinoma. Carcinoma cells are easily separated from lymph nodal cells, but immunostains for cytokeratin can highlight tumor cells, making them easier to recognize. Most lymphomas originate within lymph nodes, and by clinical presentation, lymphoma has replaced the normal architecture by monotonous sheets or nodules of cells. Further spread is via lymphatic and/or blood vessels. Lymphoma cells (small or large) are routinely subtyped with immunohistochemistry as B‐cell, T‐cell, Hodgkin cells, or otherwise. Flow cytometry and molecular techniques are also useful in subtyping malignant lymphoma. Patterns created by malignant cells are separated from benign processes that preserve normal nodal architecture and/or induce characteristic inflammatory reactions. Other malignant processes can involve lymph nodes, such as leukemia and sarcoma.
Lymph Nodes and Cancer Treatment.
Authors: Read William Lewis
Published: June 2021

The extent of regional lymph node involvement is a critical variable in the staging of all adult solid tumors. The TNM (Tumor, Node, Metastasis) staging system assigns N stage based on the careful evaluation of regional nodes. We will discuss how lymph nodes are evaluated for several different common solid tumors, and discuss how technological advances are minimizing the morbidity of this evaluation. In patients who present with involved lymph nodes, treatment for cure necessitates not only treatment of the local tumor but also treatment aimed at eradicating regional disease. Surgery, radiation or both can be used for this purpose, and we will discuss how these decisions are made and how newer treatments can improve regional disease control and survival.

Lymph node involvement on diagnosis portends a greater risk of developing distant metastatic disease, and we will discuss cases in which the presence or absence of nodal involvement is the key factor in deciding whether systemic adjuvant chemotherapy will increase the chance for cure.

Lymphoma is different from solid tumors in that it primarily affects lymph nodes as is often without a dominant primary tumor. We will discuss the diagnosis, staging and treatment of lymphoma and how this differs from that of common solid tumors. We will also discuss solid tumors that do not involve lymph nodes and how this affects staging and treatment.
Weight Loss and Dietary Changes in a Community‐Based Intervention to Reduce Cardiovascular Disease Risk in Midlife and Older Women
Authors: Folta Sara , Lichtenstein Alice , Goldberg Jeanne , Seguin Rebecca , Nelson Miriam
Published: June 2021

A trial to test the effectiveness of a community‐based program to help women reduce risk of developing cardiovascular disease was conducted in 4 counties each in Arkansas and Kansas. Counties were randomly assigned to intervention (Healthy Hearts, HH) or delayed intervention (CON) groups. The 12‐week (twice/week) program emphasized an evidence‐based heart‐healthy eating pattern and included 30 minutes of supervised aerobic activity per class. Cooperative State Research, Education and Extension agents served as program leaders. This report focuses on anthropometric and dietary changes. Of 96 initial subjects, 85 completed post‐intervention testing. At baseline, mean age was 57.8±9.4 y and BMI was 32.7±5.6 kg/m2. BMI and body weight decreased in HH subjects (−0.6±0.9 kg/m2 and −1.7±2.4 kg) and increased in CON (0.1±0.7 kg/m2 and 0.3±1.8 kg) (P<0.01 for both) as did waist circumference (−2.0±2.1 inches in HH and 0.16±1.7 inches in CON, P=0.03). Compared to CON, HH subjects reported a larger decrease in energy intake (−97±421/day and −419±391 kcal/day, respectively, P<0.01); increased fruit and vegetable servings/day (P=0.04); and decreased sweets servings/day (P<0.01). Intakes of other food groups were not significantly different. These data suggest that this community‐based program was effective in changing dietary behavior and facilitating weight loss. Supported by the Fannie E. Rippel Foundation.
Impact of copper deficiency in cattle on proteins involved in iron metabolism
Authors: Hansen Stephanie L. , Spears Jerry W.
Published: June 2021

A study was conducted examining the impact of long‐term Cu deficiency, either alone or in the presence of high Mn, on Fe metabolism in cattle. Twenty‐one Angus calves were born to cows that had been fed one of the following diets: 1) Cu adequate (10 mg supplemental Cu/kg; +Cu), 2) Cu deficient (no supplemental Cu and 2 mg supplemental Mo/kg; –Cu), and 3) Cu deficient diet plus 500 mg supplemental Mn/kg (−Cu+Mn). After weaning calves remained on the same treatment as their dam and remained on study for 275 days until harvest. Duodenal scrapings for protein isolation were collected at harvest. Plasma Cu and Fe concentrations were lower (P < 0.05) in –Cu vs. +Cu and were further decreased (P < 0.05) in –Cu+Mn vs. –Cu. Liver Cu was greater (P < 0.01) in +Cu vs. –Cu. Based on Western blotting, Cu chaperone protein (CCS) was increased (P < 0.05) in –Cu vs. +Cu but did not differ between –Cu and –Cu+Mn. Levels of hephaestin, a Cu‐dependent ferroxidase, were greater (P < 0.05) in –Cu+Mn vs. –Cu, and the iron export protein ferroportin also tended (P = 0.06) to be greater in –Cu+Mn vs. –Cu. Hephaestin and ferroportin levels were not different between +Cu and –Cu. Although liver Fe was elevated in –Cu+Mn calves compared to +Cu calves, concentrations of hephaestin and ferroportin were increased in –Cu+Mn calves, suggesting that proteins involved in Fe absorption were regulated in response to low circulating Fe rather than in response to elevated storage Fe.
Validation of the use of digital photography for estimating portion sizes
Authors: Goodell L. Suzanne , Tseui Eugenia , Hughes Sheryl O. , Nicklas Theresa A.
Published: June 2021

There is no consensus and the data are scarce on the best method for assessing diets of young children. The purpose of this study was to validate the use of digital photography as a dietary assessment method for use with preschool children. Researchers prepared and photographed 23 foods presented as ten versions of six meals. Investigators selected foods used in the estimations from a Head Start preschool lunch menu. As researchers added individual foods to a plate, they weighed each food portion to determine actual weight. From photographs on the computer, five raters estimated portion sizes for the servings of food, using a library of reference photos representing each food in 10‐gram increments. Raters viewed the meal photos and selected what they believed to be the corresponding portion size reference photo for each food on the plate. The average correlation between estimated weights across raters was 0.65. The mean difference in actual versus estimated weight of food was 1.92 grams across raters. This small mean gram difference suggests that the difference between actual and estimated nutrient analysis of foods would be very small. Thus, this method is a valid approach to collecting nutrient intake data. In the future, researchers will validate the use of this method for application in community settings including Head Start classrooms and participants’ homes.

Funded by NIH grants T32 HD007445 and R01 CA107545
Longitudinal association between waist circumference, waist‐to‐height ratio and incidence of hypertension among Chinese adults
Authors: Nguyen Tuan T , Popkin Barry M
Published: June 2021

Longitudinal study examining the association between waist circumference (WC), waist‐to‐height ratio (WHtR), and risk of cardiovascular disease among Asians is lacking. We are the first to determine cutoffs for WC and WHtR to address the increased incidence of hypertension among 18–65‐year‐old Chinese adults, using data from a China Health and Nutrition Survey 2000–2004 cohort (n = 4492). Cumulative incidence was calculated by dividing new cases of hypertension by the total at‐risk population, aged 18–65 years, in 2000. We used sex‐specific receiver operating characteristic curves to assess the sensitivity and specificity of the WC and WHtR as predictors of hypertension outcome. Four‐year cumulative incidences of hypertension, 13% and 19% for women and men, respectively, were significantly related to increase in WC and WHtR in both crude and age‐adjusted models (P for trend < 0.001). Area under the curve for the prediction of hypertension by WC or WHtR was 0.64 in crude and 0.70 in age‐adjusted models for both women and men. WC levels of 78 cm and 80 cm, WHtR levels of 0.49 and 0.48 for women and men, respectively were associated with the increased incidence of hypertension. The study shows that WC and WHtR are predictors of hypertension and that the Asian develops non‐communicable diseases at a lower WC and WHtR compared to the Westerner. WC of less than 80 cm and WHtR of less than 0.50 should be maintained by Chinese adults.

Grant Funding Source: Vietnam Educational Foundation (VEF) and NIH (R01‐HD30880, DK056350, and R01‐HD38700)
Dexamethasone Inhibit iNOSmRNA Expression and Alleviate Lung Injury in Acutely Injured Lung in Rats
Authors: Yu Zhui , LI Yinping , LI Jianguo , Jia Baohui , Zhou Qing , OuYang Jingping
Published: June 2021

In this study we intend to investigate the influence of dexamethasone (DXM) on iNOS (induced nitric oxide synthase) mRNA expression in endotoxic acutely injuried lung in rats. 30 rats were randomized into control group, ALI (acute lung injury) group and DXM group. ALI models were duplicated with lipopolysaccharide (LPS) (5mg/kg/d) by sublingual injection. In DXM group rats were injected with 10mg/kg/d DXM and 5mg/kg/d LPS sublingually at the same time. At the endpoint of 2h after injection, serum content of NO and MDA, expression level of iNOS mRNA of the lung tissue and lung histology were examined. Our results showed that after treatment with lipopolysaccharide, the content of MDA, NO and iNOSmRNA level increased remarkably ( P < 0. 05), whereas these effects of LPS were remarkably inhibited by DXM. Accordingly, DXM alleviated lung injury induced by LPS at the histological level. In conclusion, our results showed that in endotoxic acute lung injury, large amounts of iNOSmRNA expressed in the lung, which caused the outbreak of endogenic NO and subsequently mediated lung injury, while dexamethasone could inhibit the injury effects.