bluuebunny/crossref_metadata_2025 huggingface dataset:
Length‐for‐age (HAZ) progression from the 1st to the 4‐6th month among rural and urban infants in the Western Highlands of Guatemala: longitudinal and cross‐sectional perspectives (620.11)
Authors: Chomat Anne Marie , Vossenaar Marieke , Solomons Noel , Koski Kris , Scott Marilyn
Published: June 2021

Background: We have recently signaled the poorly recognized high prevalence of stunting at birth ‐ a challenge for prevention of linear growth retardation.

Objectives: To assess and compare the progression of mean HAZ and stunting rates between the 1st and the 4th‐6th mo in rural R and urban U infants in the Western Highlands of Guatemala.

Methods: Two field studies in the Province of Quetzaltenango ‐ Mam‐Mamas (a saturation survey in 8 R Mam‐Mayan‐speaking communities) and Xela‐Babies (a convenience sample from an U health clinic) ‐ included anthropometry measurement in the first 45 and at 131‐182 days of life, in a longitudinal format in both locations and in a transverse manner at the R site only. Stunting was defined as <‐2 SD of HAZ (2006 WHO growth standards).

Results: In the cohort series, the HAZ declined at the R site from an initial median of ‐1.61 (stunting prevalence 34.9%) to ‐1.79 (39.8%) (n=129; ΔHAZ ‐0.009±0.070 units/wk); and rose at the U site from ‐1.45 (25.0%) to ‐1.38 (28.3%) (n=60; ΔHAZ +0.011±0.046 u/wk). The stunting prevalence was significantly higher at 4‐6 mo at the R vs U site (p=0.012); HAZ progression was not statistically significant at either site. In the cross‐sectional samples from the R site, the progression was ‐1.89 (40.8%) (n=71) to ‐2.06 (50%) (n=60; ΔHAZ ‐0.010 u/wk).

Conclusions: This, to our knowledge, is the first report on the progression of linear growth failure within the first 6 mo of life. Within our study setting, stunting begins in utero, and is worse at the R site, with no statistically significant progression in HAZ scores between the first 6 mo of life.

Grant Funding Source: Supported by Graduate Women in Science, McGill Univ Grad Travel Award, GHR‐CAPS Doctoral Fellowship
Lactoferrin supplementation and Bifidobacteria infantis administration in a piglet model of systemic Staphylococcus aureus infection (623.17)
Authors: Reznikov Elizabeth , Hoeflinger Jennifer , Miller Michael , Donovan Sharon
Published: June 2021

Infections in infants caused by antibiotic resistant S. aureus have limited treatment options. In a clinical trial, premature infants fed formula with bovine lactoferrin (bLf) had decreased blood‐borne staphylococcal infections, but the mechanism was not known. Additionally, Lf promotes the growth of B. infantis, a predominant species in the breast‐fed infant intestine. Herein, the effect of bLf alone or in combination with B. infantis on the course of S. aureus infection was assessed. Colostrum‐deprived pigs had umbilical catheters placed at birth and were fed formula with 4g/L bLf (LF) or whey protein (CON); half of the piglets in each group were further randomized to receive B. infantis (109 CFU/day, ATCC 15697). On d7, piglets were infected intravenously with S. aureus (105 CFU/kg BW, S54F9) and euthanized on d12. Piglets had elevated (p<0.05) rectal temperature beginning at 36 h post‐infection. Piglets fed B. infantis alone or with bLF had higher (p<0.05) total WBC. No differences in weight gain or tissue weights were observed. Importantly, LF piglets had decreased (p<0.05) staphylococcal load at the kidney and lung compared to CON, with no effect of B. infantis. Thus, bLf decreases translocation of S. aureus to tissues, which could potentially reduce organ dysfunction. On‐going investigations are defining the potential mechanism by which bLf and B. infantis regulate the immune response to S. aureus infection.
Preferential factors for malnutrition intervention programs (624.15)
Authors: Yoshizawa Kazuko
Published: June 2021

Background and Objective Information on a minimum number of indicators might be useful in planning of intervention programmes. There is open access to the World Bank database of which source of information compiled from officially‐recognized international organizations. The database includes information on health and socio‐economic factors. Objective of the study is to find factors for nutrition intervention programmes by use of the World Bank database. Method Database for multiple regression analysis in this study was prepared by use of secondary information by use of the database of World Development Indicators and Global Development Finance (2012). Indicators focused were acute and chronic malnutrition, literacy rate, mortality rate, life expectancy, primary school enrolment rate, birth rate, 6 month exclusive breast feeding, rate of DPT vaccination and access to safe water. Results Malnutrition as a dependent variable is statistically associated with literacy rate of female aged greater than 15 years, GDP per capita, DPT vaccination rate and 6month exclusive breast feeding (R2 =0.56, p<0.000). Similarly statistically significant factors for child malnutrition are literacy rate of male aged greater than 15 years, GDP per capita, DPT vaccination rate and 6month exclusive breast feeding (R2 =0.52, p<0.000): however, male literacy is not an important factor with female literacy in the model. Discussion and Conclusion Non‐significance of the factor of male literacy in the multiple regression alaysis could be due to the strong correlation between male literacy and female literacy (r=0.945). Preferential factors for nutrition intervention programmes are female literacy, vaccination and 6 month exclusive breast feeding. Acknowledgements I would like to thank Natsumi Suzuki and Saki Sugita for important suggestion.
Impact of iron‐folic acid supplementation on birth size and birth weight in Pakistan (624.20)
Authors: Nisar Yasir , Dibley Michael
Published: June 2021

Objective To examine the effect of iron‐folic acid (IFA) supplementation on perceived birth size and birth weight using Pakistan DHS 2006‐07.

Methods Information from 5,692 most recent (with 5 years) live‐born infants was used. The primary outcomes were perceived birth size and birth weight and the main exposure was any maternal use of IFA during pregnancy. Birth weight was reported for only 10% of live births in PDHS 2006‐07. Analyses used multivariate logistic regression adjusted for X potential confounders and the sampling design.

Results The risk of small birth size babies was significantly reduced by 18% (aOR: 0.82, 95% CI 0.71, 0.96, p=0.013) for mothers who used any IFA supplements compared to no IFA use. Mother who started IFA in the first trimester, significantly reduced the risk of small birth size babies by 19%. With antenatal IFA, the risk of low birth weight was significantly reduced by 51% for <2000 grams and non‐significantly by 60% and 18% for <1500 grams and <2500 grams respectively.

Conclusion Antenatal IFA supplementation significantly reduced the risk of small birth size and low birth weight babies in Pakistan. The greatest protective effect of antenatal IFA was for infants with birth weight <1500 grams.
Vitamin D and calcium: the relationship of dietary intakes and blood levels in obese minority adolescents (628.11)
Authors: Yeh Yulyu , Brogan Kathryn , Naar‐King Sylvie , Tang Jiangqi , Jen Kai Lin, Catherine
Published: June 2021

Vitamin D deficiency, defined as 25OH vitamin D < 50nmol/L, and serum calcium level are associated with obesity. However, limited research has investigated the relationship of the active form of serum vitamin D, 1,25OH2 vitamin D (1,25(OH)2 D), in obese minority youth. This study examined the level of 1,25(OH) D, serum calcium and it’s relationship with dietary vitamin D, calcium intake in a convenience sample of 135 obese African American Adolescents (oAAA) (mean age: 14.0±1.4yrs, 66% girls, mean BMI percentile: 98.4±4.9, mean BMI 37.8±7.4kg/m2). Laboratory blood assays were conducted for 1,25(OH)2 D and calcium. The Block Food Frequency Questionnaire (BFFQ) was used to assess dietary intake. Both 1,25(OH)2 D (46.5±19 pg/ml) and serum calcium (9.3±0.9 mg/dl) levels were within the desirable range for adolescents (30‐100pg/ml and 8.5‐10.8mg/dl respectively). However, self‐reported intake of dietary vitamin D (97.9±75.6 vs 600 IU, p<0.01) and calcium (538±297 vs1300 mg/d, p<0.01) were significantly lower than the dietary reference intakes. No relationship emerged between 1,25(OH)2 D, serum calcium and dietary intake. A negative correlation was found between 1,25(OH)2 D and BMI (p<0.05). The findings suggested oAAA have sufficient 1,25(OH)2 D and serum calcium levels, however an inverse relationship exists between 1,25(OH)2 D and BMI. Another source of vitamin D that may impact serum 1,25(OH)2 D levels is exposure to UV light. Further investigation to understand the relationship of vitamin D and weight is warranted.
Serum folate and colorectal adenoma in Korean adults (628.18)
Authors: Park Young Mee , Cho Chang Ho , Kim Sung Hi , Lee Jung Eun
Published: June 2021

We investigated the association between serum folate levels and colorectal adenoma in a case‐control study of Korean adults. Participants underwent colonoscopy, and provided blood specimens and information on their socio‐demographic status and other risk factors for colorectal adenoma in a university hospital. Serum folate levels were measured by using the electrochemiluminescence immunoassay (ECLIA). Colorectal adenoma cases were determined through colonoscopy and histologic examinations. We included 113 cases (58 men and 55 women) of colorectal adenoma and 255 controls (69 men and 186 women). We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) using a multivariate logistic regression model. After adjusting for potential confounding factors, we found no significant association between serum folate levels and colorectal adenoma; multivariate ORs (95% CIs) for the highest tertile compared to the lowest tertile were 0.86 (0.31 to 2.39) in men and 1.12 (0.51 to 2.46) in women. In summary, we did not observe that serum folate levels were associated with colorectal adenoma in Korean adults.

Grant Funding Source: This study was supported by National Research Foundation of Korea (2011‐0011028)
Dietary carbohydrate intake and dyslipidemia in Korean adults (628.19)
Authors: Park Hye Won , Kim Kyunga , Kim Mi Kyung , Lee Jung Eun
Published: June 2021

The aim of our study was to evaluate the associations of total carbohydrate intake and glycemic index (GI) and load (GL) with lipid profiles in a prospective study of Korean adults. We included a total of 4,327 participants aged 40‐69 years followed for 4 years since 2001 and provided blood specimens at a follow‐up. Carbohydrate intake, GI, and GL were calculated from the relevant food items on a validated food frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) for low high‐density lipoprotein cholesterol (HDL‐C), high low‐density lipoprotein cholesterol (LDL‐C), and high triglyceride (TG) were analyzed using the logistic regression models. Replacing protein or fat intake (g/d) with total carbohydrate intake (g/d) was associated with lower HDL‐C levels, and higher levels of LDL‐C and TG; multivariate ORs (95% CIs) comparing top quartile with bottom quartile were 1.26 (0.99‐1.60; p‐trend = 0.03) for low HDL‐C, 1.31 (1.05‐1.64; p‐trend = 0.03) for high TG, and 1.33 (1.10‐1.61; p‐trend = 0.01) for high LDL‐C. Replacing percentage energy from fat or protein with percentage energy from carbohydrate was associated with lower HDL‐C levels, and higher levels of LDL‐C and TG; multivariate ORs (95% CIs) comparing top quartile with bottom quartile were 1.40 (1.08‐1.79; p‐trend = 0.006) for low HDL‐C, 1.33 (1.05‐1.68; p‐trend = 0.03) for high TG, and 1.40 (1.15‐1.71; p‐trend = 0.004) for high LDL‐C. However, there was no association for either GI or GL. In summary, we found that high total carbohydrate intake was associated with unfavorable lipid profile in Korean adults. However, our study does not support the hypothesis that low levels of GI or GL are associated with improved lipid profile.

Grant Funding Source: This study was supported by Sookmyung Women's University Research Grant
Disordered eating behaviors and attitudes of females with cystic fibrosis (628.7)
Authors: Quick Virginia , Byrd‐Bredbenner Carol
Published: June 2021

Cystic fibrosis (CF), an autosomal recessive disorder, occurs in 1:2500 live births or a rate of 0.4 cases/1000 individuals 蠄 26 years. CF etiology and treatment may put CF patients at increased risk for disordered eating. This study intensively recruited female young adults with CF to complete an online survey of disordered eating behaviors and attitudes. Participants (n=9) were 20.6±2.7SD years, mostly White (87.5%), and normal weight (22.4±2.5SD). Over one‐third reported health status as fair or poor, exercised excessively 蠅2x/month, and binge ate with loss of control. A quarter engaged in self‐induced vomiting and medicine misuse (e.g., pancreatic lipase enzyme) 蠅2x/month to control weight. One met the Eating Disorders Examination Questionnaire, 6th ed. clinical cut‐off for eating, weight, and shape concerns. A follow‐up survey (n=4) found most had good communication and relationships with health care providers and were currently satisfied with medical treatment. Only one participant had received eating disorder information from a health care provider (RD). This study expands our limited understanding of disordered eating in patients with this relatively rare disorder and suggests that health care providers be aware of, screen for, and monitor potential disordered eating behaviors and attitudes in females with CF and offer early intervention.

Grant Funding Source: Supported in part by the intramural research program of the National Institutes of Health(NIH/NICHD)
Translating science into the 2015 Dietary Guidelines (630.12)
Authors: Goodwin Stephanie , Casavale Kellie , Piercy Katrina , Mosher Amber , McPeak Holly , Olson Richard
Published: June 2021

The development of the U.S. dietary policy utilizes an evolving process that now provides a rigorous, evidence based approach for developing the Dietary Guidelines for Americans (DGA). Objective To describe updates to the current scientific process for developing the DGA. Methods The U.S. Departments of Health and Human Services (HHS) and Agriculture (USDA) jointly appoint a Dietary Guidelines Advisory Committee (DGAC) consisting of nationally recognized experts in nutrition and health. The DGAC examines the state of current scientific evidence using systematic reviews, data analyses, and/or food pattern modeling analyses. Additional sources of information may include scientific evidence‐based reports, input from expert guest speakers, and oral and written comments from the public. Results The DGAC prepares a report for both HHS and USDA Secretaries that provide recommendations for the next edition of the DGA. The Departments jointly review the DGAC’s recommendations and develop and publish the revised DGA policy document every 5 years. Conclusion The DGA provide science‐based advice on how food, nutrition, and physical activity can promote the health of the U.S. population ages 2 years and older and help reduce risk for and burden of major chronic diseases. The 2015 DGA will form the basis for nutrition and related health policies in programs, services, and activities across the Federal government.
Mother’s altered representation of children’s weight: how culture creates shared patterns of social evaluation (630.8)
Authors: Gregori Dario , Hochdorn Alexander , Vecchio Maria , Baldi Ileana
Published: June 2021

Objective. An altered representation of parents regarding the weight status of their children may foretell difficulties in implementing effective policies against obesity. The following study aims to understand in a cross‐national setting the psychological and social processes, implied in forming collectively shared and legitimized representations of what parents consider as desirable in terms of weight. Study design. The OBEY‐AD is a cross‐sectional study realized in 9 countries enrolling 2635 children aged 3‐11 years. Children’s BMI CDC z‐scores have been computed and categorized as Normal, Overweight, Obese and Underweight. Mothers have been asked to judge the weight status of their children according to these categories. Results. 567 children resulted as obese or overweight (21%). Out of them, 22% (413) were not recognized by mothers as suffering from an excess of weight. Such figures range from up to 38% in Italy down to 14% in Germany. Overall agreement between perceived and actual weight status of children was very poor (Kappa 0.19,p<0.001). Surprisingly, 5% of the overweight/obese children were considered as underweight by their mothers (up to 12% in Brazil). Misperception of children’s weight status seemed to be significantly related to family socio‐economic status and in particular to parents’ education. Conclusions. This study quantifies the extent of the so‐called social desirability bias, namely mother’s unconscious attitude to adapt empirical evidence to more culturally legitimized ideal‐types of what their children’s weight status is expected to be. Considered than mothers are most often responsible for family care and nutrition choices, in particular in lower socio‐economic strata of the population, there’s a potential for undermining effectiveness of policies against obesity. If parents do not recognize their childs’ physical condition, they can’t intervene to diminish the risk factors for obesity and its related complications.
Estimating distributions of usual 24‐hour sodium excretion from timed‐spot urines in adults 18‐39 years (632.11)
Authors: Wang Chia‐Yih , Carriquiry Alicia , Chen Te‐Ching , Loria Catherine , Pfeiffer Christine , Liu Kiang , Sempos Christopher , Perrine Cria , Swanson Christine , Cogswell Mary
Published: June 2021

We developed and tested calibration equations from spot urine specimens to estimate the distribution of usual 24h sodium excretion (24UNa). A convenience sample of 407 adults, 18‐39 y, (54% female, 48% black) collected each void in a separate container for 24h; 133 collected a second 24h urine 4‐11 d later. We selected 4 timed voids (morning [M], afternoon [A], evening [E], overnight [O]) from each 24h collection. Participants were randomly assigned to test (n=247) or validation (n=160) groups. Total sodium excreted in each of the 4 one‐spot and 6 combined two‐spot (e.g., M+A) urines from the test groups were used with covariates to develop sex‐specific equations for predicting 24UNa using Fuller’s error‐in‐the‐equation measurement error model. Equations applied to the validation data were used to estimate usual 24UNa distributions with the Iowa State University method. Mean bias in predicting the median of 24UNa with one‐spot urines ranged from ‐69 to 1617 mg for men and ‐72 to ‐9 mg for women, and with two‐spot urines from ‐124 to 115 mg and ‐50 to 9 mg, respectively. Mean bias in predicting percentiles (5th, 25th, 50th, 75th, and 95th) did not differ from 0 (p=0.06‐0.90) for men or women using an O void or combined E+O urine. Our method to estimate population distribution of 24UNa, which uses timed‐spot urine specimens and accounts for day‐to‐day variation and covariance between measurement errors, merits further investigation.
Fluid balance of Olympic male basketball players before and during performance (633.4)
Authors: Harrison Kellene , Mockford Thomas , Kern Mark
Published: June 2021

Fluid balance of Olympic male basketball players was assessed prior to and throughout performance and possible relationships between hydration status and physical load were examined during three pre‐Olympic basketball games. Pre‐ and post‐game urine specific gravity (USG) and body weight as well as fluid intake during the games were determined. Physical load was assessed by accelerometry/GPS (MinimaxX, Catapult). Overall, 54% of players were hypohydrated entering at least one of three games. Forty percent in Games 1 and 2 and 67% of players in Game 3 lost 蠅1% of body mass. No associations were detected between fluid intake and hydration or physical load. Negative correlations were observed for pre‐game USG and late game physical load (Q3: r=‐.603, p<.039; Q4: r=‐.909, p<.034). Pre‐game USG was not related to fluid intake during the game. A negative correlation existed between USG change and physical load (r=‐.627, p<.023) when all games were averaged. These data suggest that poor pre‐game hydration may be related to late game fatigue and that dehydration during play as evidenced by change in USG is related to lower physical load. Voluntary fluid intake failed to compensate for a poor pre‐game USG.
Variable iron status among twins and triplets at birth (636.3)
Authors: Ru Yuan , Pressman Eva , Guillet Ronnie , Cooper Beth , Katzman Philip , Caveglia Sarah , O'Brien Kimberly
Published: June 2021

Iron (Fe) uptake and transfer to the fetus is mediated by the placenta. The objectives of this study were to examine the degree of variability in neonatal Fe status between siblings born to women carrying twins or triplets and to investigate determinants of neonatal Fe status in this group. A total of 67 women carrying multiples aged 30.6 ± 5.2 were enrolled between the 1st and 3rd trimester of pregnancy. Maternal blood across pregnancy and umbilical cord blood at birth were utilized to assess neonatal Fe status including Hb, serum ferritin (SF), transferrin receptor (TfR), erythropoietin (EPO), and hepcidin. Neonates were born at week 34.5 ± 2.9 of gestation and weighed 2188 ± 613 g; 69% of neonates were preterm and 72% had low birth weight (LBW). Approximately 19% of neonates were anemic (Hb<13 g/dL) at birth, 27.3% had SF < 76 µg/L and 18% had TfR > 8.5 mg/L. Mean cord SF was 120 ± 82 µg/L (n=70); a value comparable to the 50th percentile using normative data. Total body iron (TBI) in neonates was calculated using birth weight (kg), cord Hb (g/dL) and functional Fe in tissues as described by Georgieff et al with adjustment for gestational age at birth. TBI averaged 171 ± 27.3 mg per neonate at birth (n = 65) was significantly correlated to amnionicity (p = 0.0005). Ratio between maternal and neonatal TBI was 0.61 ± 0.1. Significant variability was evident in cord SF (n = 70, p = 0.0002), TfR (n = 74, P=0.0001) and neonatal birth weight (p < 0.0001) among siblings. High rates of preterm birth/LBW and low TBI stores at birth suggest the need for more data on determinants of Fe status and anemia in this group.

Grant Funding Source: Supported by the Gerber Foundation
Dietary fatty acid composition modulates parallel shifts in the metabolic profiles of mice and gut microbiota populations (637.7)
Authors: Muller Catherine , Walter Jens , Chekal Jessica , Peterson Daniel , DiRusso Concetta
Published: June 2021

Recent research showed that dietary fat impacts gut microbiota (GM) composition with consequences for host metabolism, particularly in the case of saturated fatty acids (SFA). However, little is known about the impact of other types of fatty acids (FA) on the interaction between GM and host. In this study, we evaluated the impact of diets enriched in health‐promoting polyunsaturated fatty acids (PUFA) or highly unsaturated fatty acids (HUFA) in comparison to SFA on host‐GM interactions. C57Bl/6 mice were placed on normal‐fat (7%) diets with the lipid portion enriched in one of the following: SFA, PUFA, HUFA, or a SFA/HUFA mixture. SFA increased body and liver weight, and liver triglycerides compared to the HUFA‐containing diets. HUFA resulted in the lowest amount of total liver FA and the highest amount of fecal excretion. In the liver, FA synthase and steroyl‐CoA desaturase expression was increased with SFA and PUFA compared to HUFA‐containing diets, while expression of Lipocalins 2 and 13 showed the opposite trend. In the gut, Bacteroides were significantly increased in the SFA/HUFA diet compared to the other three diets. Bifidobacteria were increased in the mice fed PUFA and HUFA‐enriched diets. In conclusion, dietary PUFA and, especially, HUFA enrichment resulted in beneficial changes in metabolic parameters and, speculatively, GM. Continuing research focuses on determining the relationship between the two.

Grant Funding Source: Supported by University of Nebraska Agricultural Research Division Strategic Research Initiatives
In vivo Immunostimulatory properties of S22 extracted Celosia argentea Linne in C57BL/6 mice (638.2)
Authors: Park Bongkyun , Kim Jiyun , Lee Heeweon , Pyo Suhkneung
Published: June 2021

S22 is a purified extract from Celosia argentea Linne. Many herbal extracts have been known to have multiple biological activities including stimulation of immune response. However, the biological effects of S22 are not known well. In the present study, we examined immunostimulatory effect of S22 on peritoneal macrophages and splenic immune cells from six week‐old mice that were fed either a control or oral administration 50 mg/kg of S22 for 14 days. The results from MTT assay showed that S22 enhanced macrophages‐ or NK cells‐mediated cytotoxicity to tumor cells. In addition, S22 significantly increased phagocytosis capacity of peritoneal macrophage. The colorimetric nitric oxide (NO) assay revealed that NO production was not increased by S22 in peritoneal macrophage. However, the results from ELISA assay demonstrated that S22 significantly increased the production of Interleukin‐6 (IL‐6), Tumor necrosis factor alpha (TNF‐α) and Interferon alpha (IFN‐α), but not INF‐β in peritoneal macrophage. Overall, our results suggest that S22 may provide some leads in the development of new immunomodulatory drugs.
Effect of supplementation with astaxanthin in CD1 mice submitted to chronic stress in Peyer's patches (638.6)
Authors: Martinez‐Carrillo Beatriz , Oros Rigoberto , Delgadillo Angeles , Valdés‐Ramos Roxana
Published: June 2021

Astaxanthin is a powerful antioxidant, it decreases oxidative stress, inflammatory response and increases the immune response. Chronic stress stimulates the secretion of hormones that affect the immune system, such an effect has not been studied at the level of the intestinal mucosa. The objective is to determine the effect of supplementation with astaxanthin in CD1 mice submitted to chronic stress in Peyer's patches of the intestinal mucosae. 32 CD1 10‐week old mice were used, 30‐35 g/weight, divided into 4 groups: Control (CL), chronic stress (CS), astaxanthin (A) Chronic stress plus astaxanthin (EC + A); astaxanthin was administered orally at doses of 4 mg/g. An unpredictable chronic stress scheme was used. T‐lymphocytes (CD3+, CD4+ and CD8+) and B (CD19+) were determined by flow cytometry. CD3+ T‐lymphocytes increased as follows: EC (40.57 ± 9.88), EC + A (30.49 ± 6.46), A (38.98 ± 9.06) compared with CL (27.47 ± 7.77), with F = 4.88 (p 蠄 0.004); at the expense of TCD4+ cells: CL (23.14 ± 5.85), EC (30.86 ± 6.28), EC + a (33.82 ± 7.41), A (28.92 ± 5.61), F = 9.04 (p 蠄 0.001) and TCD8+, CL (3.51 ± 1.24), EC (5.83 ± 1.65), EC + A (6.68 ± 1.35), A (8.26 ± 1.67) F = 10.24 (p 蠄 0.001). B cells showed no significant differences. Astaxanthin enhances the immune response in Peyer's patches, altering the normal proportion TCD4+ / CD8+.

Grant Funding Source: Universidad Autónoma del Estado de México, Promep
Effect of MonaVie Rest œ on sleep duration and sleep quality in moderately stressed subjects (647.23)
Authors: Talbott Shawn , Perkins Logan , Young Devin
Published: June 2021

BACKGROUND: A variety of herbal teas, including Fennel (Foeniculum vulgare), Lemon balm (Melissa officinalis), and Chamomile (Chamaemelium nobile) are used to induce relaxation, improve sleep, and treat insomnia. OBJECTIVE: We conducted a pilot study in 9 moderately stressed subjects to assess changes in sleep duration, latency, and quality following consumption of a combination product (MonaVie RestTM) intended to induce relaxation and promote restful sleep. The product contains a blend of fennel, lemon balm, and chamomile in a ready‐to‐drink tea. METHODS: We used a portable sleep‐tracking device (Zeo Sleep Manager, Zeo Inc) to measure differences between sleep patterns following control (no tea) and supplemented (post‐tea) conditions. Subjects wore the sleep‐tracking EEG electrode headband nightly for two weeks, alternating between one night with no tea and one night consuming the tea. Results were averaged for “tea” versus “non‐tea” nights. RESULTS: Following 2 weeks of alternate‐night tea consumption, improvements were found on nights when tea was consumed for measures of sleep latency (‐24%; 10 v. 13min), sleep duration (+8%; 416 v. 384min), minutes in REM sleep (+7%; 140 v. 130min), and overall sleep quality (+8%; 79% v. 72%). CONCLUSION: These preliminary results suggest that supplementation with MonaVie Rest promotes restful sleep (latency and duration) and improves overall sleep quality.
Innate immune modulatory effects of elderberry polysaccharides in murine macrophage cell line RAW 264.7 (647.40)
Authors: Lu Chi‐Hua , Lei Wei , Fritsche Kevin
Published: June 2021

Introduction: Botanical‐derived polysaccharides have been suggested to modulate innate and adaptive immune responses in mammals, and elderberry consumption has also been linked to fewer sick days during cold/flu season. Therefore, we hypothesized that the immune modulatory effects of elderberry may be partially contributed by its polysaccharides.

Experimental design: The polysaccharides from freeze‐dried whole elderberry (EP) were prepared by hot water and ethanol precipitation method. Intracellular reactive oxygen species (ROS), extracellular nitric oxide (NO), and gene expressions were measured from sample‐treated RAW 264.7 cells.

Results: Ranging from 2 μg/mL to 30 μg/mL, EP stimulated the production of ROS/NO in a dose‐dependent manner, and the 30 μg/mL EP yielded maximum ROS/NO production as the 100 ng/mL Escherichia coli lipopolysaccharides (LPS) did. A PCR array for mouse NF‐kB pathway (PAMM‐025A, Qiagen) was used to compare the expression of 84 genes 4 hr after treatment of RAW cells with EP or LPS. Eighty of the 84 genes were found to be similarly expressed in the EP‐treated compared to LPS‐stimulated RAW cells.

Conclusion: Elderberry polysaccharides stimulated immune responses in RAW 264.7 cells through NF‐kB pathway by its LPS‐like activity. Future research is undertaken to further differentiate activities of botanical polysaccharides from potential botanical endotoxins.

Grant Funding Source: NIH P50AT006273
Antimutagenic and antioxidative activities of sandy tea and its in vitro anticancer effect on TCA8113 human tongue squamous carcinoma cells (647.7)
Authors: Zhao Xin
Published: June 2021

Sandy tea is a traditional and popular drink in China. The aim of this study was to determine the antioxidant activity, antimutagenic activity of sandy tea and its in vitro anticancer effect on TCA8113 human tongue squamous carcinoma cells. The antioxidant effects were determined by measuring the 1,1‐diphenyl‐2‐picryhydrazyl (DPPH) free radical舉 and hydroxyl radical舉scavenging activity. The sandy tea extract demonstrated high antioxidant activity in the assays of DPPH and hydroxyl radical舉scavenging activity. At concentrations of 1.25 and 2.5 mg/plate, sandy tea exhibited anti‐mutagenicity with N‐methyl‐N'‐nitro‐N‐nitrosoguanidine (MNNG) in the Salmonella typhimurium TA100 strain. MTT assay and RT‐PCR assay were employed to check the anticancer effects on TCA8113 cancer cells. At the concentration of 200 µg/ml, sandy tea (81%) showed the best inhibitory effect on TCA8113 human tongue squamous carcinoma cells compared to the other concentrations. Compared with 100 µg/ml and 50 µg/ml of sandy tea extracts, 200 µg/ml of sandy tea induced apoptosis, up‐regulated mRNA expressions of Bax, caspase‐3 and caspase‐9, and down‐regulated Bcl‐2 expression. These results suggest that sandy tea possesses good antioxidant activity and anticancer effect on TCA8113 human tongue squamous carcinoma cells.
Right ventricular remolding, dysfunction, and pulmonary arterial hypertension following left ventricular myocardial infarction (648.7)
Authors: Huber Jason , Platt Mathew , Romanova Nadya , Wright David , Simpson Jeremy
Published: June 2021

Assessment of cardiac function in patients with heart failure (HF) is generally limited to the evaluation of systolic and diastolic function of the left ventricle (LV). Right ventricle (RV) dysfunction is considered a sequelae of LV HF. However, the pathogenesis of RV remodeling has received little attention. Our objective was to investigate the progression of RV function following LV myocardial infarction (MI). Methods: Left and right ventricle remodeling was assessed using invasive hemodynamics, molecular and histomorphometric approaches at 2, 4 9 and 18 weeks post‐MI induced by permanent ligation of the left anterior descending artery. Results: Invasive hemodynamics revealed a decrease in LV contractility and systolic blood pressure and an increase in end diastolic pressures (EDP), which remained stable until 18 weeks post‐MI. In contrast, RV systolic pressure and contractility initially increased at 2 weeks prior to a drop off from 4 to 18 weeks post‐MI. In addition RV EDP was elevated at all time points. Re‐expression of fetal genes occurred in both ventricles with greater change of several genes in the RV as compared to the LV. Histological analysis revealed significant increases in cardiomyocyte cross sectional area and fibrosis in both LV and RV. Conclusion: Significant RV remodeling and dysfunction is evident immediately following a LV MI and may play an important and underappreciated role in the development of LV HF.

Grant Funding Source: Supported by Canadian Institute of Health Research
The therapeutic use of atropine in diabetic neuropathy (651.12)
Authors: Mota Andre , Frizzi Katie , Calcutt Nigel
Published: June 2021

Diabetic neuropathy, a neurological complication of diabetes, is associated with significant rates of morbidity and mortality. Since limited therapeutic approaches currently exist for diabetic degenerative neuropathy, we investigated the efficacy of novel therapeutic approaches. Specifically, we focused on the use of atropine, an alkaloid and commonly‐used drug that affects the autonomic nervous system. To investigate the therapeutic potential of atropine, insulin‐dependent (type‐1) diabetes was induced in mice via injection of streptozotocin (STZ), producing insulin deficiency and hyperglycaemia within 3 days. Atropine (2% in gel) was applied daily to the eyes or feet of mice. Testing for neuropathy was performed on the 4th and 8th weeks of the study. Severity of neuropathy was determined by assessing paw sensitivity to touch and heat and by measuring nerve conduction velocity. Corneal nerves were also imaged in live animals throughout the study by corneal confocal microscopy (CCM) and captured images will be used to measure the nerve fiber density by stereological techniques (values in % occupancy). At the end of the study, we will also measure cutaneous innervation of skin biopsies by counting intra‐epidermal nerve fibers immunostained with PGP 9.5 under a light microscope (values in #/mm of dermal:epidermal junction). Our initial results suggest that atropine may prevent onset of behavioral and electrophysiological indices of neuropathy in diabetic mice, supporting use of this drug as a possible therapeutic approach to the treatment of diabetic neuropathy.
Dual agonism of peripheral cannabinoid CB1/CB2 receptors suppresses cardiac myocyte hypertrophy (652.9)
Authors: Lu Yan , Anderson Hope
Published: June 2021

The development of endocannabinoid‐based therapies is hindered by psychoactive side effects mediated by central CB1 receptors. We determined the effect of CB‐13, a peripherally‐restricted agonist of CB1/CB2 receptors, on cardiac myocyte hypertrophy. Endothelin‐1 (ET‐1, 0.1 μM) induced hypertrophy of rat cardiac myocytes as measured by cell enlargement (122±4%), protein synthesis ([3H]‐leucine incorporation; 147±13%), and fetal gene expression (brain natriuretic peptide mRNA levels; 426±88%) (p<0.05 vs. controls). CB‐13 attenuated all hypertrophic indicators and activated two anti‐hypertrophic signals: AMP‐activated protein kinase (AMPK) and eNOS through phosphorylation at Thr172 and Ser1177, respectively. eNOS activation was ablated by shRNA knockdown of AMPK, and disruption of signaling through AMPK (knockdown) or eNOS (L‐NIO, 1 μM) blocked the anti‐growth effects of CB‐13. CB‐13 also improved mitochondrial function by trafficking through AMPK and PGC‐1α (a driver of mitochondrial biogenesis). ET‐1‐induced mitochondrial depolarization, as assessed by subcellular compartmentalization of the potential‐sensitive dye, JC‐1, was inhibited by CB‐13. In conclusion, dual agonism of peripheral CB1/CB2 receptors is protective in the context of cardiac myocyte hypertrophy and mitochondrial dysfunction vis‐à‐vis crosstalk between AMPK, eNOS and PGC‐1α.
microRNA upregulation and acetaminophen protein adducts in acetaminophen toxicity in children (653.2)
Authors: Gill Pritmohinder , Bhattacharyya Sudeepa , Harrington Alison , Letzig Lynda , McCullough Sandra , James Laura
Published: June 2021

While acetaminophen (APAP) overdose accounts for 13% of cases of acute liver failure in children, the etiology of 50% of cases of acute liver failure is unknown. Circulating microRNA‐122a has been reported to be increased in mice with APAP toxicity and in adults with liver failure. Acetaminophen protein adducts, microRNA (miR) and alanine aminotransferase (ALT) levels were compared in 12 children hospitalized for acetaminophen overdose and in 15 healthy controls. Median (range) values for ALT were 1266 IU/L (41‐6072) for APAP overdose subjects and 16 IU/L (10‐30) for healthy controls. Median acetaminophen protein adduct values were 1.1498 nmols/mL (0.2803‐3.7533) for APAP overdose subjects and 0.0053 nmols/mL (0‐0.0097) for healthy controls. Consistent with data in adults, a 192 fold change (median) for miR‐122a was observed in the serum samples of APAP subjects compared to healthy controls (Mann Whitney p<0.05). miR‐378, a regulator of CYP2E1, was increased by 31 fold (median) in APAP overdose subjects compared to healthy controls (p<0.05). To examine relationships between biomarkers, a linear mixed effects model was developed using repeated measures in a subset of subjects. miR‐122a correlated with adducts (p<0.05), but not with ALT, while miR‐378 correlated with both adducts and ALT (p<0.05). Further study of miRNA dysregulation in association with acetaminophen protein adducts in APAP toxicity is indicated.
The role of β‐arrestin 2 and GRK5/6 in development of differential tolerance to morphine in the colon and ileum (653.3)
Authors: Bhave Sukhada , Datta de Dipanjana , Dewey William , Akbarali Hamid
Published: June 2021

Morphine, the most often used analgesic for chronic pain, is associated with severe side‐effects including nausea, abdominal pain, constipation. Development of tolerance is the major drawback of morphine that limits its clinical efficacy. Tolerance develops to many of the effects of morphine but not to constipation. Previous findings from our lab suggest that tolerance to chronic morphine develops in the ileum but not in the colon. β‐arrestin 2 is implicated with development of tolerance to morphine. Anti‐nociceptive tolerance is associated with uncoupling of GPCRs following binding of β‐arrestin 2 to GRK‐phosphorylated opioid receptors. In the present study we elucidate the role of β‐arrestin 2 in differential response to chronic morphine in the colon and ileum. We identified 4 out of 13 known β‐arrestin 2 splice variants (ARRB2‐006, 005, 013 and 001) in the colon and ileum by RNA‐seq. RT‐PCR analysis confirmed the presence of these variants in both tissues. The mRNA expression of each of the four β‐arrestin 2 variants was 10‐fold higher in the ileum as compared to the colon. On chronic morphine treatment, the expression of all the β‐arrestin 2 variants decreased in the ileum by 80% but remained unchanged in the colon. Furthermore, the mRNA expression levels of GRK5 and GRK6 decreased in the ileum on chronic morphine treatment by about 50‐70% but not in the colon. We, thus, hypothesize that down regulation of β‐arrestin 2 and GRK 5/6 is associated with development of tolerance in the ileum.

Grant Funding Source: Supported by NIH DA024009 and DK046367
Effects of metformin on bethanechol‐induced contractions of the lower esophageal sphincter (653.8)
Authors: Peuler Jacob , Murphy Patrick , Phelps Laura
Published: June 2021

Metformin is widely used in the treatment of diabetes. We have shown 1) that at millimolar concentrations it can markedly inhibit contractions of the isolated rat bladder as induced by the muscarinic receptor agonist bethanechol and 2) that this effect can be antagonized by the potassium (K) channel blockers tetraethylammonium (TEA) and 4‐aminopyridine (4AP) but not barium or glyburide (The FASEB Journal 2012 ; 26 :1049.2). Thus, metformin may be opening some but not other subpopulations of K channels known to exist in smooth muscle cell membranes of the bladder wall. We tested for these same effects in the lower esophageal sphincter of the rat because 1) by contracting this tissue bethanechol is used to treat gastroesophageal reflux disease (which is common in diabetic patients) and 2) metformin is known to reach millimolar concentrations in gastrointestinal tissues (including the esophagus) after standard oral dosing. Our results were the same as we observed previously in rat bladder. Thus, metformin’s ability to inhibit muscarinic receptor‐mediated smooth muscle contractions may be related in general to an ability to open both TEA‐sensitive and 4AP‐sensitive K channels in all smooth muscle cell membranes.
Diuretic activity in rats: the ethanol and aqueous extracts of rhubarb (657.1)
Authors: Yin Lu , Feng Ya‐Long , Tian Ting , Chen Hua , Chen Dan‐Qian , Zhao Ying‐Yong
Published: June 2021

Aim: Rhubarb (Da Huang in Chinese), a worldwide herb, is commonly used as an ingredient of numerous herbal formulations to treat a large amount of diseases related to constipation, hepatitis, cholecystitis, as well as diabetic nephropathy (DN) and chronic renal failure (CRF). The aim of this study is to evaluate the diuretic activities of ethanol extract (EE) and aqueous extract (AE) of rhubarb in saline‐loaded rats to explore their potential mechanism and future research opportunities. Methods: Urinary excretion rate, pH and electrolyte excretion were measured in the urine after orally administered to rats by EE (200 mg/kg, 400 mg/kg and 800 mg/kg) and AE (500 mg/kg, 1000mg/kg and 2000 mg/kg). Results: In the study, both EE and AE increased the urinary excretion rate. Nevertheless, AE enhanced the urinary output slightly while EE significantly increased the urinary excretion. The three doses of EE produced an increase Na+, K+ and Cl‐ excretion. EE at 200 mg/kg and 400 mg/kg doses increased pH values while 800 mg/kg dose showed decrease in pH values. All the three doses of AE showed an increase in the Na+, K+ and Cl‐ excretion significantly. The three doses of AE decreased pH values meaningfully. Conclusions: These date suggest that it is ethanol extracts instead of aqueous extracts of rhubarb that presents a remarkable diuretic effect. The results provide a quantitative basis to explain the use of rhubarb as a diuretic agent. Research will be continued to elucidate the mechanism of the diuretic action particularly the structure‐activity relationship of the bioactive components in the most bioactive fractions.

Acknowledgements:This study was supported by the Program for the Changjiang Scholars and Innovative Research Team in University (No. IRT1174), the National Natural Science Foundation of China (No. 81001622) and the Administration of Traditional Chinese Medicine of Shaanxi (13‐ZY006).
Triptolide inhibits HuR‐dependent TNF‐α and IL‐6 mRNA stabilization and protein expression in Raw264.7 cells (657.6)
Authors: Jiang Zhenzhou , Zhang Luyong
Published: June 2021

Triptolide is a diterpenoid isolated from the plant Tripterygium wilfordii Hook. F and has been used for the treatment of a variety of autoimmune and inflammatory diseases including rheumatoid arthritis. In the present study, triptolide was found to inhibit LPS‐induced TNF‐α and IL‐6 expression in Raw 264.7 cells. The aim of this study was to determine if the RNA‐binding protein HuR plays a key role in triptolide regulating on TNF‐α and IL‐6 expressions. Methods: The mRNA degradation of TNF‐α and IL‐6 was analyzed by real‐time PCR in Actinomycin D assay. The HuR shuttling from nucleus to cytoplasm was detected by Immunofluorescence staining. Immunoprecipitation of HuR‐mRNA complexes was performed to assess the association of endogenous HuR with TNF‐α and IL‐6 mRNAs. The effect of triptolide on TNF‐α and IL‐6 3’‐ untranslated region (UTR) was detected by GFP reporter gene assay. Results:Triptolide decreased the half‐life of TNF‐α and IL‐6 mRNA dramatically and it inhibited 3’‐UTR fluorescence reporter gene activity. Meanwhile, triptolide inhibited the HuR shuttling from nucleus to cytoplasm. After triptolide treatment, decreased TNF‐α and IL‐6 mRNA in pull‐down experiments with anti‐HuR antibodies was observed, indicating that the decreased cytoplasmic HuR is responsible for the decreased mRNA. Conclusions: HuR might have a key impact on anti‐inflammatory and anti‐cancer effects of triptolide.
Effects of the kappa opioid antagonist nor‐binaltorphimine on cocaine vs. food choice and extended‐access cocaine intake in rhesus monkeys (658.6)
Authors: Hutsell Blake , Banks Matthew , Negus Steve , Rice Kenner
Published: June 2021

The dynorphin/κ opioid receptor system (KOR) has been implicated as one potential neurobiological target for treating cocaine addiction. This study determined effects of the KOR antagonist nor‐binaltorphimine (nor‐BNI) on cocaine self‐administration by rhesus monkeys responding under a novel procedure that featured two daily components: (1) 2‐h choice sessions (9‐11am) when monkeys could choose between food pellets and cocaine (0‐0.1 mg/kg/inj, IV), and (2) 20‐h “extended access” sessions (noon‐8am) when only cocaine (0.1 mg/kg/inj) was available under a fixed‐ratio schedule to promote high daily cocaine intakes. After 14 days of responding under this novel procedure, nor‐BNI (3.2 mg/kg, IM) was administered, and responding was evaluated for an additional 14 days. Consistent with previous studies, cocaine maintained a dose‐dependent increase in cocaine choice, and monkeys also self‐administered cocaine throughout the extended access component. Total daily intake averaged 7.5±0.66 mg/kg cocaine. Nor‐BNI treatment had no significant effect on cocaine choice either during or after withdrawal from extended cocaine access. These results suggest the dynorphin/KOR system does not play a major role in cocaine self‐administration under these conditions. These results also do not support the utility of KOR antagonists as medications to treat ongoing cocaine use in persons dependent on cocaine.

Grant Funding Source: Funded by NIH grant R01DA026946.