bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving the management in a complex system of medical and social rehabilitation of the Republic of Kazakhstan (1185.5)
Authors: Bayserkina Farida
Published: June 2021

To study the patterns of formation and structure the causes of childhood disability and to develop a management model of preventive, treatment and rehabilitation measures to reduce disability of children in the Republic of Kazakhstan.

We studied the nature and frequency of using medical advices to perform them at home, the organization of practical training of parents, the massage techniques, as well as some other medical rehabilitation activities, the awareness of parents on a number of issues related to the disease and treatment of child health clinics role in health education of the family.

The study of the relationship of a family to conduct rehabilitation treatment in outpatient conditions using questionnaires and interviews revealed that the vast majority (97.2%) of parents who thought it as a mandatory.

Guidelines for the rehabilitation at home through physiotherapy sessions and conducting the certain types of massage carried out even less (48.9%). According to experts the prescribed treatment was not completed due to lack of health education work with parents during the course of rehabilitation. The survey of mothers found that more than one third (36.5%) did not know the cause of the disease and its possible consequences in connection with what the child is not engaged regularly or not at all designated procedures, which reduced the effectiveness of the treatment of children with disabilities.
Organization of work experience in prevention of sexually transmitted infections and viral human immunodeficiency‐acquired immunodeficiency syndrome in commercial sex worker groups (1185.7)
Authors: Danbayeva Zh.
Published: June 2021

According to WHO experts, community health at the present time is linked to the 55‐60% of the lifestyle and personal behavior of the person.

Due to the current epidemiological situation in the Republic of Kazakhstan on HIV and sexually transmitted infections (STIs), has acquired special urgency on behavioral factor that focuses on youth.The main epidemiological role in the spread of STIs owned by high‐risk groups: sex workers, injecting drug users.

The traditional restrictive practices of STI clinics in relation to CSW and cooperation in this area with the police led to negative attitudes of sex workers community towards public health services. One of the ways to achieve the transformation of consciousness of CSW is the organization of CSW‐friendly clinics.In addition to CSW, other vulnerable populations, including injecting‐drug users, men who have sex with men, adolescents should be provided with medical care in such clinics. Creating a friendly offices (clinics) and professionally providing assistance to persons in high‐risk behaviorswill help prevent infections, sexually transmitted diseases and human immunodeficiency virus‐acquired immunodeficiency syndrome in groups. The deployment of these clinics on the basis of STI clinics and AIDS centers ensures access of vulnerable groups to health care and prevention of STI\HIV at the level at which it is accessible by other people. It is important that the friendly relaxed atmosphere is created in the clinic, allowing members of high‐risk behavior groups to freely consult with medical professionals.Medical assistance and advisory services should not be linked to the provision of any information about the patient's personality.Frequent causes of failure of vulnerable groups from seeking medical organizations are concerns about the lack of confidentiality, potential limitations associated with permanent residence.
Determinants of the gap between breastfeeding knowledge and practices in Vietnamese mothers (119.1)
Authors: Nguyen Tuan , Nguyen Phuong , Hajeebhoy Nemat
Published: June 2021

We conducted this analysis to examine determinants of the knowledge‐practice gap in early and exclusive breastfeeding (BF). In a cross‐sectional survey, we interviewed 10,834 mothers with children aged 0−23 months old in 11 of 63 provinces of Viet Nam about BF practices, knowledge, barriers and support. The knowledge‐practice gap was defined when a mother knew about the benefit but did not perform the corresponding practice. The proportion of mothers with a knowledge‐practice gap in early and exclusive BF was 34% and 66%, respectively. Mothers were ~10% less likely to have a knowledge‐practice gap in early BF if they received BF advice and support from a health worker during pregnancy or at birth (P < 0.05; Poisson regression). The gap, however, was 60%, 140% and 20% more likely to occur among those with hospital delivery, cesarean delivery and BF difficulty, respectively (P < 0.05 for all). For exclusive BF, a 25% reduction in the gap was found if a mother believed that people who are important to her support exclusive BF (P < 0.001). A 5% increase in the gap was found among mothers who were exposed to infant formula advertising daily (P < 0.01). To reduce the knowledge‐practice gap in early BF, programs should focus on strengthening support by health staff and minimizing health‐facility related barriers. For exclusive BF, programs should focus on addressing socio‐cultural barriers.

Grant Funding Source: Bill & Melinda Gates Foundation, through Alive & Thrive Initiative, managed by FHI360
BMI and race/ethnicity differences on satiety and food intake among women (120.7)
Authors: Park Eunyoung , Huang Yancui , Edirisinghe Indika , Kelley Michael , Kergoat Sophie , Inui Taichi , Randolph Jody , Burton‐Freeman Britt
Published: June 2021

Obesity has increased significantly over the last 30 years, with racial/ethnic groups (RE) disproportionately affected. Few investigations have examined the effect of RE on hunger/satiety and food intake behavior. In a 2‐arm cross‐over study, we examined the relationship of body mass index (BMI) and RE to subjective satiety and snack intake using a modified preload paradigm with gum chewing (GUM) or no gum control (CTL) as a means to enhance the satiety response to lunch preload. Fifty unrestrained healthy weight and obese (1:1 ratio) women completed the study. RE: Caucasian, African America (AA), Asian, Hispanic, balanced between BMI groups. GUM compared to CTL resulted in significant suppression of hunger, desire to eat and prospective consumption (p<0.05 for all controlling for BMI and RE). Snack intake was marginally reduced by GUM (p=0.08). Post‐hoc analyses indicated significant (p<0.05) differences by RE on all subjective satiety measures, which corresponded to RE snack intake 3 h after lunch. Effects appeared to be specific to AA women and sweet snacks (p=0.003) and were not predicted by differences in insulin, glucose or CCK responses. These data offer new insight for understanding the influence of RE on satiety and snack intake.

Grant Funding Source: Supported by Wrigley (A subsidiary of Mars Incorporated)
Metabolic syndrome symptoms are reduced in C57BL/6J mice fed high‐fat diets supplemented with apple and cherry extracts, quercetin, and ellagic acid (121.2)
Authors: Smith Sarah , Zhao Bingxin , Kaiser Clive , Shay Neil
Published: June 2021

We are evaluating metabolic improvements and gene expression changes in mice fed phytochemicals present in apples, sweet cherries, and polyphenol‐rich extracts derived from these fruits. Polyphenol‐rich extracts were produced by solid phase extraction and column chromatography. Extracts and purified compounds were mixed into a high‐fat (60% of total kcal) obesigenic rodent diet and fed to C57BL/6J mice along with low‐fat and high‐fat control diets. Mice fed the high‐fat control diet became obese and lost normal glucose control. Mice fed high‐fat diets containing these extracts and purified compounds exhibited improved metabolic parameters compared to mice fed the high‐fat control diet. For example, after a 6‐week feeding period, high fat‐fed mice provided quercetin (Q) or ellagic acid (EA) in their diet gained 17% and 12% less body fat, respectively (P< 0.05) despite consuming equal amounts of diet. Apple (AE)‐ and cherry extract (CE)‐fed mice gained 30% and 12% less body fat, respectively (P<0.05), again with no reduction in food intake. Six‐hour fasted blood glucose levels were measured and AE‐, CE‐, Q‐, and EA‐supplemented HF‐fed, these mice had lower baseline blood glucose levels and both AE‐ and Q‐supplemented mice had reduced area under the curve (glucose x time) in a 2‐hour glucose tolerance test (P < 0.05). Compounds present in apples and cherries including quercetin and ellagic acid appear to be producing beneficial metabolic effects in this model of metabolic disease.

Grant Funding Source: Blue Mountain Horticultural Society
Dark chocolate low in polyphenols increases BMI in normal weight and overweight adults (121.3)
Authors: Farhat Grace , Al‐Dujaili Emad , Drummond Sandra , Fyfe Lorna
Published: June 2021

Polyphenols are antioxidants with potential health benefits. Dark chocolate (DC) is one of the highest food sources of polyphenols (mainly flavanols). Two research areas have emerged recently; the effect of cocoa flavanols on body weight and the role of polyphenols in counteracting the negative effects of chocolate’s high fat content. The aim of this study was to determine the effect of DC supplementation with or without polyphenols on body mass index (BMI), fasting blood glucose and blood triglycerides (TG). Participants (61;22 overweight and 39 normal weight) took part in a randomized controlled parallel trial. Volunteers received 20g of either PRDC (polyphenol‐rich DC) (500mg) or placebo DC with negligible amount of polyphenols for 4 weeks. Anthropometric measures and a blood sample were collected at baseline and after 4 weeks. Results showed a significant increase in BMI (0.17 ±0.32, p=0.007) following placebo DC consumption, while no changes in the PRDC group were noted (p=0.821). There was also a significant increase in fasting blood glucose and TG levels in the placebo group only (p=0.041 and p=0.008, respectively). These results suggest the potential role of polyphenols in body weight control and raises concerns over the polyphenol content of DC in the market. Further studies are needed on the benefits of DC before supporting the regulation of chocolate’s polyphenol to ensure its beneficial effect on health.
The micronutrient profile of the typical American diet enhances colorectal carcinogenesis in mice (123.4)
Authors: Benninghoff Abby , Monsanto Stephany , Larson Deanna , Hintze Korry , Ward Robert , Lefevre Michael
Published: June 2021

The new total Western diet (TWD) for rodents mimics typical human dietary intakes of macro‐ (carbohydrates, proteins, and fats) and micronutrients (vitamins and minerals) on an energy density basis for rodents. The objective of this study was to determine the impact of TWD on colorectal carcinogenesis using the azoxymethane + 1% dextran sodium sulfate mouse model of inflammation‐associated colon cancer. We compared colon cancer incidence, multiplicity and size in TWD‐fed mice to those provided a commercial 45% fat diet‐induced obesity diet and AIN93G, which is optimized for rodent health. Also, we included two additional test diets to evaluate the contribution of the micronutrient (vitamin‐ and mineral‐modified diet, [VMM]) or macronutrient (macro‐modified diet [MM]) contents of the TWD. Consumption of the TWD or VMM diet significantly increased colon tumor multiplicity by 2‐fold and size by more than 3‐fold compared to the AIN93G control (p<0.01), whereas consumption of the DIO or MM diets did not enhance colon tumorigenesis. Collectively, these observations point to a critical role of dietary micronutrients in colon carcinogenesis. Importantly, this promoting effect is likely unrelated to the metabolic syndrome phenotype induced by the high fat diet, as our prior data showed that TWD did not alter body composition, body weight gain or glucose tolerance. Moreover, our observations emphasize the need to take into account the micronutrient content of rodent basal diets when modeling typical U.S. nutrition in pre‐clinical animal experiments in order to improve the translation of these studies to human nutrition and dietary intervention programs. We are currently performing genome‐wide analysis of gene expression in colon mucosa obtained from control‐, TWD‐ and DIO‐fed mice. Also, an additional diet trial using the APCmin genetic mouse model of intestinal cancer is underway to confirm our observations.

Grant Funding Source: Supported by the Utah Agricultural Experiment Station
Arthropod aloft: the anatomical and biomechanical origins of aerial behavior (13.1)
Authors: Dudley Robert
Published: June 2021

Diverse animal taxa exhibit remarkable aerial capacities, including jumping, aerial righting, parachuting, gliding, landing, controlled maneuvers, and flapping flight. The origin of wings in hexapods greatly facilitated subsequent lineage diversification, but both the paleobiological context and possible selective pressures for wing evolution remain contentious. Larvae of various arboreal hemimetabolous insects, as well as many canopy ants, demonstrate the capacity for directed aerial descent in the absence of wings. Aerial control in the ancestrally wingless archaeognathans also suggests that flight behavior preceded the origins of wings in hexapods. In evolutionary terms, the use of of winglets and partial wings to effect aerial righting and gliding maneuvers could select for enhanced appendicular motions, and ultimately lead to powered flight. Flight behaviors that involve neither flapping nor wings are likely much more widespread than is currently recognized. Further characterization of the sensory and biomechanical mechanisms used by these aerially capable taxa can potentially assist in reconstruction of ancestral winged morphologies and facilitate our understanding of the origins of flight.
Electronic health records identify community‐specific risk factors for childhood obesity (130.2)
Authors: Tomayko Emily , Flood Tracy , Tandias Aman , Arndt Brian , Buckingham William , Hanrahan Lawrence
Published: June 2021

The objective of this study was to assess the relationship of community economic hardship index (EHI), race/ethnicity, and childhood obesity using the University of Wisconsin (UW) Public Health Information Exchange (PHINEX) database, which links deidentified electronic health records with census block group data. The EHI is a composite score of community‐level factors (crowded housing, poverty, income, education, unemployment, and number of dependents <18 or >64 years old) that addresses multiple determinants of health. Records from 85,963 children (2‐17 years old) seen at UW clinics from 2007‐2012 were included. The obesity prevalence was 13.4%, and significant disparities were detected (ranging from 11.9% for non‐Hispanic Whites to 23.0% for Hispanics). Childhood obesity was significantly associated with EHI (r=0.489, p<0.001), with mixed‐effects modeling indicating the relationship between EHI and obesity significantly differed among racial/ethnic groups (p=0.01). The magnitude of change in obesity percentage with increasing EHI scores was greater for non‐Hispanic Whites compared to Hispanic and Black children. Our findings demonstrate the utility of linking electronic health records with census data to rapidly and easily identify community‐specific risk factors that allow researchers, practitioners, and public health professionals to tailor community interventions and measure program effectiveness.
Usual dietary energy density distribution is associated with excess body weight in Mexican children (130.3)
Authors: Aburto Tania , Cantoral Alejandra , Hérnandez‐Barrera Lucia , Carriquiry Alicia , Rivera Juan
Published: June 2021

Studies suggest a positive association between dietary energy density (DED) and body weight. Evidence in children is inconclusive. Our objective was to compare usual DED distributions of non‐overweight and overweight children adjusting to minimize random and systematic errors.

We used 24 hour recall data from 2367 children between 5 and 11 y old from the 2012 National Health and Nutrition Survey. Repeated measures of 24 h recalls were obtained in a random sample (10%) to estimate usual intake distributions using the Iowa State University method. Implausible dietary reports were identified. The relationship between DED and body weight status was evaluated using multivariate linear regression models.

35.1% of the children in the sample were overweight (including obesity). After adjustment for covariates, DED of overweight children was 2.9 kcal/100g higher than that of non‐overweight children (p=0.066). Adjusting also for measurement error and restricting analysis to plausible reporters, DED was 9.2 kcal/100 g higher in overweight compared to non‐overweight children (p<0.0001).

Results show a positive association between DED and body weight in Mexican children and the importance of appropriate adjustments for random and systematic errors in dietary associations. They also suggest the need of strategies to reduce DED, such as a tax on energy‐dense low‐quality foods to tackle obesity in Mexico.
Blood folate concentrations among women of childbearing age by race/ethnicity and acculturation, NHANES 2001‐2010 (130.5)
Authors: Marchetta Claire , Hamner Heather
Published: June 2021

Objective: The objective of this research was to assess the differences in serum and red blood cell (RBC) folate concentrations between non‐Hispanic white (NHW) women and Mexican American (MA) women and among MA women by acculturation factors. Methods: Data from the 2001‐2010 NHANES were used to examine how blood folate concentrations differ among NHW or MA women of childbearing age, in general and stratified by folic acid containing supplement use. Women were considered supplement users if they reported any use of a folic acid containing supplement in the prior 30 days. Results: MA women with lower acculturation factors (i.e. those who reported primarily speaking Spanish, being born in Mexico, or living in the United States < 15 years) had lower serum and RBC folate concentrations compared to NHW women and to their more acculturated MA counterparts. Consuming a folic acid containing supplement can decrease these disparities, but MA women, especially lower acculturated MA women, were less likely to report using supplements. Conclusions: Public health efforts to increase blood folate concentrations among MA women should consider acculturation factors when identifying appropriate interventions.
Study of Latinos: Nutrition & Physical Activity Assessment Study (SOLNAS) (130.6)
Authors: Mossavar‐Rahmani Yasmin , Shaw Pamela , Wong William , Sotres‐Alvarez Daniela , Gellman Marc , Van Horn Linda , Stoutenberg Mark , Daviglus Martha , Wylie‐Rosett Judith , Siega‐Riz Anna Maria , Ou Fang‐Shu , Prentice Ross
Published: June 2021

Objective: In SOLNAS we investigate measurement error in self‐reported diet of Hispanics in the US by ethnicity (Cuban, Dominican, Mexican, Puerto Rican, Central and South American) who are prone to obesity and related co‐morbidities.

Methods: In 485 participants aged 18‐74 yrs, doubly labeled water and urinary nitrogen were used as objective biomarkers of energy and protein intake, respectively. Self‐report was captured from two 24‐hour dietary recalls (24HR). We estimate the bias of 24HR with multivariate regression.

Summary: Energy intake was underestimated on average 24.1% (men 20.5%; women 26.2%) and protein by 15.9% (men 11.6%; women 18.4%). Participant characteristics associated with underestimation of energy were higher BMI, being female, older age and Hispanic ethnicity. For protein, these characteristics were higher BMI, older age, being a non‐smoker, Spanish speaking and Hispanic ethnicity.

Conclusions: There is systematic under‐reporting of energy and protein intake that varies significantly by Hispanic ethnicity and language preference. Calibration equations that correct for subject‐specific error in reporting can reduce bias in diet‐disease associations.

Grant Funding Source: Supported by NIH/NHLBI grant #5 R01 HL095856
Vegetarian and non‐vegetarian dietary patterns and nutrient profile differentials between the sexes and Blacks and Whites (130.7)
Authors: Rizzo Nico , Fraser Gary
Published: June 2021

Background: Dietary patterns are of great interest as they reflect choices of food combinations over time and may contribute to the development or prevention of disease.

Objective: To compare nutrient intakes of diverse dietary patterns between races and sexes.

Design: Cross‐sectional study of 71751 subjects (mean age 59 years, 65% women, 76% white) from the Adventist‐Health‐Study‐2. Data was collected between 2002 and 2007. Participants completed a 204‐item validated semi‐quantitative food frequency questionnaire. The dietary patterns compared are: non vegetarian, semi vegetarian, pesco vegetarian, lacto‐ovo vegetarian and strict vegetarian. ANCOVA was used to analyze differences in nutrient intakes by dietary patterns stratified by sex and race.

Results: Nutrient intakes varied more strongly between dietary patterns than between the sexes or blacks and whites. Nutrient intakes were more dissimilar between blacks and whites than between the sexes. Blacks hada higher proportion of non vegetarians and pesco vegetarians. Supplement intakes were markedly higher in women than in men and higher in whites than in blacks. Blacks had lower intakes of nutrients often associated with dairy products and higher intakes of soy protein and marine fatty acids.

Conclusions: Dietary patterns characterized by differences in meat and dairy consumption show marked differences in nutrient composition that can have health implications. Differences between the sexes and black and white subjects should be considered when interpreting demographic differences in nutritional studies.

Grant Funding Source: Supported by National Institutes of Health Grant 1R01‐CA‐94594
Effect of the reduction of sodium content of processed food on sodium intake in Brazil: the National Dietary Survey, 2008‐2009 (130.8)
Authors: de Moura Souza Amanda , da Silva Nalin de Souza Bárbara , Nogueira Bezerra Ilana , Sichieri Rosely
Published: June 2021

Brazilian government and food industry made a technical agreement to establish voluntary, gradual, and sustainable targets to reduce the sodium content of processed foods. In order to evaluate how the sodium reduction targets for processed foods will change sodium intake, day‐1 food records from 34,003 respondents (蠅10yrs) in the 2008‐2009 Brazilian National Dietary Survey were analyzed. The 2013 Brazilian sodium reduction targets were used as a benchmark to evaluate the effect of the reduction of sodium content of processed foods on mean sodium intake. Sodium reduction targets were applied to 23 food groups. Application of the proposed sodium reduction targets results in 7.2% reduction in the mean sodium intake (3190 to 2957 mg/day). This reduction was similar among all age and sex groups; however mean sodium intake still exceed the tolerable upper limit intake level of 2300 mg/day. Our findings indicate that sodium reduction targets have a small effect on sodium intake. To reduce sodium intake successfully, sodium reduction strategies are necessary to improve consumer awareness to incorporate education campaigns in order to modify eating habits.
Making a case for a new “pay‐as‐you‐go” CSA model (132.8)
Authors: Freedman Marjorie , King Juliana
Published: June 2021

Community supported agriculture (CSA) is a unique food distribution system which allows subscribers to obtain produce directly from local farmers. Literature examining this direct marketing channel remains limited to the traditional model of an upfront financial investment from subscribers, who receive, in return, a weekly produce box for a growing season. The aim of this study was to provide insight into the financial viability of a more flexible CSA “pay‐as‐you go” model, which might appeal to a larger subscriber base, and to compare characteristics of subscribers who order a box weekly to those who order less frequently. An email‐linked survey was sent to current and former J&P Organics CSA subscribers in Northern CA. A total of 557 participants answered questions on ordering frequency, reasons for joining/maintaining a subscription, satisfaction, behavior change, influences on ordering patterns and demographics. Respondents were categorized into 4 groups based on order frequency (group 1: weekly [16.6%], group 2: 2‐3x/month [39%], group 3: 1x/month [16.2%], group 4: <1x/month [28.1%]). Most respondents were female (74.5%); 64% were from 2 member households; and 68% were Caucasian. Most participants increased their consumption of organic and fresh food, and tried new fruit and vegetables. The most notable distinctions in responses were between weekly subscribers as compared to infrequent users. For example, more weekly subscribers (40.9%) as compared to those in group 4 (14.3% ) consumed all the produce in their boxes. Group 2 emerged as an important financial contributor, with similar characteristics and subscription lengths as group 1. These findings support the idea that a more flexible ”pay‐as‐you‐go” model can help small farms increase their market share, revenue, and long‐term viability.
Effects of diet‐induced obesity on the expression patterns of a lactoferrin receptor variant, omentin‐1, in growing mice (133.2)
Authors: Nonnecke Eric , Bronstein Sarah , Lönnerdal Bo
Published: June 2021

The pathophysiology ascribed to increased adiposity is due in part to perturbation of tissue‐specific and systemic levels of pleiotropic cytokines. A circulating variant of the lactoferrin receptor (LfR), known as omentin‐1, a novel adipokine, is differentially expressed in humans with metabolic disease (e.g., type II diabetes) and aberrant immune activation (e.g., Crohn’s disease); however, the cellular origin(s) and effector function(s) of omentin‐1 remain to be fully elucidated. We investigated the effect of diet‐induced obesity (DIO) on omentin‐1 expression patterns in growing mice. At 28 days postpartum, male C57BL/6N mice were fed a control (CTRL: 10% fat) or a high fat‐sucrose (HFS: 45% fat) diet for 14 wks. Protein analysis showed that omentin‐1 was constitutively expressed across various tissues. HFS‐fed animals gained more weight (~20%) than CTRL‐fed animals by 14 wk. Using oral glucose‐ and i.p. insulin tolerance tests, these animals were shown to display marked glucose intolerance at 4, 8, and 12 wk and insulin resistance at 5, 9, and 13 wk. HFS‐fed animals had increased plasma leptin at 6, 10, and 14 wk and elevated hepatic triglycerides at 14 wk. Fasting omentin‐1 concentrations were higher in CTRL‐fed animals at 4 wk compared to HFS‐fed animals but not later, suggesting that omentin‐1 expression patterns are modulated by DIO in young mice and may signal an early alteration in global inflammatory status.
Differences between the ex vivo and in vivo anti‐inflammatory activities of Aronia mitschurinii (black chokeberry) polyphenols in C57/BL6 mice (134.3)
Authors: Bolling Bradley , Brand Mark , Draghi Andrew , Martin Derek
Published: June 2021

The objective of this study was to characterize the anti‐inflammatory potential of Aronia mitschurinii ‘Viking’ (black chokeberry). Male C57/BL6 mice were fed AIN‐93 chow or chow supplemented with 4.5% lyophilized aronia ad libitum for 4 wk. Primary mouse splenocytes were also incubated with aronia extract or its polyphenol constituents ex vivo. IL‐6 and IL‐10 were determined by ELISA analysis of cell‐culture supernates. Aronia extract, quercetin, and cyanidin‐3‐arabinoside co‐incubation inhibited LPS‐stimulated splenocyte IL‐6. In contrast, there was no difference in LPS‐stimulated splenocyte IL‐6 production as a result of aronia feeding. Quercetin and hydroxycinnamic acids co‐incubation inhibited LPS‐stimulated splenocyte IL‐10. Aronia extract co‐incubation increased unstimulated splenocyte IL‐10 to 140% of the control. Similarly, colonic tissue IL‐10 was 101% greater in aronia‐fed mice than control. In contrast, aronia supplementation did not inhibit LPS‐induced colonic IL‐10, IL‐6, IL‐17 or TNF‐α. Therefore, although aronia polyphenols exhibit distinct structure‐function anti‐inflammatory activity in vitro in splenocytes, these actions are not realized after aronia feeding in healthy mice. However, aronia feeding may benefit colons of healthy mice by increasing IL‐10.

Grant Funding Source: Supported by the University of Connecticut Diet and Health Initiative and USDA Hatch CONS0080
A polyherbal dietary intervention preserves functional islet β‐cell mass in non‐obese diabetic mice (134.8)
Authors: Burke Susan , Karlstad Michael , Reel Danielle , McEntee Michael , Whelan Jay , Collier James
Published: June 2021

Type 1 diabetes mellitus results from autoimmune‐mediated destruction of pancreatic islet β‐cells. Dietary supplements that decrease blood glucose levels or prevent losses in functional β‐cell mass are currently sought for treatment of autoimmune‐mediated diabetes. We fed female non‐obese diabetic (NOD) mice, a model of spontaneous autoimmune diabetes, a diet supplemented with herbal extracts (32g total herbal extracts in 12kg of diet) over a 12 week period. The mice consumed isocaloric diets without (controls) and with polyherbal supplementation (PHS) ad libitum starting at a prediabetic stage (age 6 weeks) for 12 weeks. Control mice developed hyperglycemia (>180mg/dL) within 16 weeks (n = 8). By contrast, mice receiving the PHS diet did not develop hyperglycemia by 18 weeks (n = 8). After 18 weeks, there was a 31.9% increase in insulin‐positive cell mass in PHS mice relative to controls (n = 8). We also detected a 26% decrease in CD3+ lymphocytic infiltration in PHS mice relative to controls (n = 8). In vitro assays confirmed a 25% decrease in β‐cell expression of the chemokines CCL2 and CXCL10 with PHS media relative to controls. We conclude that daily polyherbal supplementation may be beneficial towards reducing severity or delaying time of onset of autoimmune‐mediated diabetes.
Developmental exposure to maternal folic acid intake programs vascular NADPH oxidase expression in mice (135.3)
Authors: Aleliunas Rika , Golbidi Saeid , Olson Jesse , Glier Melissa , Laher Ismail , Devlin Angela
Published: June 2021

Nutritional adversity during development influences the cardiometabolic adaptation in adulthood. Recent birth cohort studies from South Asia have reported an association between maternal folate and vitamin B12 imbalance and increased child adiposity and insulin resistance. In Canada, where folic acid fortification was implemented in 1998, women have adequate folate status but 1 in 20 may be vitamin B12 deficient in the early stages of pregnancy. The goal of our project was to determine the effects of developmental exposure to high folic acid and low vitamin B12 status on vascular function. Female wild‐type C57BL/6J mice were fed diets high in folic acid, with (HFA+B12) and without (HFA‐B12) adequate vitamin B12, or a control diet for six weeks prior to breeding, and during pregnancy and lactation. Offspring were weaned onto control or a western diet (WD), consisting of 45% fat and 35% carbohydrate, and fed for 20 weeks. We assessed vascular endothelial function and NADPH oxidase subunit (Nox2) expression as indicators of vascular health. Mesenteric arteries from WD‐fed mice with developmental exposure to HFA‐B12 showed decreased relaxation (10%) in response to acetylcholine relative to control and HFA+B12 groups. In the control diet group basal nitric oxide production was lower (10%) in mice with developmental exposure to HFA (with and without vitamin B12). Nox2 subunit expression was decreased in aortae of mice with developmental exposure to high folic acid in both control‐fed and WD‐fed mice. These findings suggest that the developmental exposure to high maternal folic acid programs vascular health in adult offspring mice.

Grant Funding Source: NSERC
Vitamin B12 status in pregnant women and their children in India (135.6)
Authors: Finkelstein Julia , Kurpad Anura , Thomas Tinku , Bose Beena , Samuel Tinu , Srinivasan Krishnamachari , Duggan Christopher
Published: June 2021

Objective: To examine the prevalence and determinants of poor infant vitamin B12 status at birth, and determine the associations between maternal and infant vitamin B12 status.

Methods: 366 pregnant women participating in a vitamin B12 supplementation trial in India were monitored to assess maternal vitamin B12 status in pregnancy and its association with infant vitamin B12 status at 6 weeks of age. Binomial and linear regression were used to evaluate the associations between maternal and infant vitamin B12 status.

Results: 51% of mothers were vitamin B12 deficient (<150pmol/L) at baseline, and 47% of infants were vitamin B12 deficient at 6 weeks of age. Maternal vitamin B12 concentrations during 3 trimesters (T) were significantly correlated with infant vitamin B12 status (T1: r=0.19, p=0.10; T2: r=0.39, p<0.01; T3: r=0.56, p<0.0001); with stronger correlations in B12‐supplemented women (T1: r=0.42, p<0.01; T2: r=0.55, p<0.001; T3: r=0.55, p=0.001). After adjusting for vitamin B12 supplementation, higher maternal B12 concentrations at baseline predicted increased infant vitamin B12 levels (p=0.06), and infants born to vitamin B12‐deficient mothers were 1.6 times more likely to be vitamin B12 deficient (p=0.05).

Conclusions: Inadequate maternal vitamin B12 status during pregnancy predicted increased risk of infant vitamin B12 deficiency.

Grant Funding Source: Supported by: NICHD, ICMR
Parenteral nutrition after preterm birth compromises brain development (137.3)
Authors: Buddington R , Choudhri A , Sable H , Chizhokov V , Buddington K
Published: June 2021

Parenteral nutrition (PN) is essential for preterm infants intolerant of enteral nutrition (EN), but is associated with gastrointestinal atrophy and dysfunction, liver pathology, and increased risks of sepsis. We discovered that growth and maturation of the brain after preterm birth is also compromised by PN. Preterm pigs delivered at 92% of gestation (representative of 32 week preterm infants) were provided PN for 24 h before 10 more days of nutritional support provided either by continued PN or conversion to full EN using formula. Fluid volumes, energy, and nutrients were comparable. Providing PN resulted in higher body weight gain, but at necropsy brain mass was 13% lower compared with EN pigs (P<0.01).Assessments of activity revealed a rapid divergence between PN and EN pigs (P<0.01) and neurocognitive skills of PN pigs after 10 days were diminished (P<0.02). The delayed development of motor skills corresponded with a smaller cerebellum. Diffusion tensor imaging revealed myelination of major CNS nerve tracts was reduced among PN pigs. The compromised brain development caused by PN is a novel finding, though the roles of specific nutrients are uncertain. Advances in PN for preterm infants are hindered by a poor understanding of nutrient requirements and a reliance on clinical trials with preterm infants. The preterm pig is a translational animal model for screening PN solutions, accelerating advances in nutrition support, and providing insights for the design of clinical protocols to evaluate improved PN solutions.
Modulation of paternal B vitamin intake does not affect tumorigenesis but does alter growth trajectory in Apc1638N mouse offspring (137.7)
Authors: Sabet Julia , Mason Joel , Bronson Rodrick , Crott Jimmy
Published: June 2021

Modulation of paternal B vitamin intake does not affect tumorigenesis but does alter growth trajectory in Apc1638N mouse offspring Sabet JA1,2, Mason JB1,2, Bronson RT3, Crott JW1,21Friedman School of Nutrition Science and Policy at Tufts University, Boston, MA2Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA3Rodent Histopathology Core, Harvard Medical School, Boston, MA It is well established that maternal nutrition can impact on offspring health and physiology; however the contribution of paternal nutrition to offspring health is less understood. We have shown that maternal B‐vitamin supplementation suppresses, while deficiency promotes, intestinal tumorigenesis in a mouse model of colorectal cancer. We sought to determine whether modulating paternal intake of vitamins B2, B6, B12, and folate similarly alters intestinal tumorigenesis in offspring. Male APC1638N mice were fed diets containing control, deficient, or supplemental quantities of vitamins B2, B6, B12, and folate for 8 wk before mating with control‐fed wild‐type females. APC1638N offspring were maintained on control diets until 28 wk of age. No differences in tumor incidence, size or grade were found between offspring of different paternal diet groups. Overall, male offspring exhibited a greater tumor incidence and burden than female offspring. Among female offspring, growth was significantly retarded in the progeny of deficient and supplemented fathers compared to control fathers. Modulation of paternal B‐vitamin intake prior to mating did not alter offspring intestinal tumorigenesis but did impact offspring growth in a sex‐specific fashion in APC1638N mice. Analyses to profile DNA methylation changes in sperm and gene expression changes in offspring liver are underway.

Grant Funding Source: Supported by NCI grant 1 R03CA162505‐1
Characterization of a hepatocyte nuclear factor 4 alpha gene signature in hepatocellular carcinoma (144.11)
Authors: Walesky Chad , Gunewardena Sumedha , Yoo Byunggil , Li Ren , Edwards Genea , Apte Udayan
Published: June 2021

Previous studies from our laboratory using conditional knockout mice and functional genomics have shown that HNF4α inhibits hepatocyte proliferation and deletion of HNF4α promotes DEN‐induced hepatic tumors in mice. To further delineate the role of HNF4α in hepatic tumorigenesis, we performed RNA‐seq analysis on DEN‐induced HCCs obtained from HNF4α‐null, WT, and normal mouse liver tissue. A total of 2152 genes were differentially expressed in HCC obtained from HNF4α‐null mice. Comparative genomics analysis of RNA‐seq data with HNF4α ChIP‐seq data revealed a novel gene signature for tumors lacking HNF4α. This analysis revealed 322 genes, which were at least 2‐fold differentially expressed and contained a putative HNF4α binding site. We hypothesize that liver tumors that lack HNF4α activity tend to be highly aggressive and metastatic. We tested this hypothesis using the HNF4α gene signature to characterize the HNF4α activity status in various mouse models of HCC and are currently conducting a prospective analysis of human HCC samples. Our results have revealed a novel set of genes regulated by HNF4α specifically involved in HCC pathogenesis that may be useful as a prognostic tool in HCC diagnosis.

Grant Funding Source: Supported by NIH Training Grant T32 ES007079
Coagulation driven platelet activation reduces injury and fibrosis in chronic liver disease (144.3)
Authors: Joshi Nikita , Kopec Anna , Towery Keara , Cline Holly , Williams Kurt , Flick Matthew , Luyendyk James
Published: June 2021

Previous studies suggest that platelets and fibrin(ogen), components of the hemostatic system, reduce hepatocellular injury and inhibit liver fibrosis in models of cholestasis. However, the molecular pathways linking fibrin polymerization and platelet activation to liver injury during cholestasis are not known. We hypothesized that platelet activation by thrombin‐mediated protease activated receptor (PAR)‐4 signaling and fibrin engagement of the αIIBβ3 integrin on platelets are key events linked to inhibition of hepatic injury and fibrosis in a mouse model of cholestasis. To test this hypothesis, mice expressing a mutant form of fibrin(ogen) incapable of binding αIIBβ3 (FibγΔ5), mice lacking PAR‐4 and wild‐type (WT) mice were fed a diet containing the bile duct toxicant alpha‐naphthylisothiocyanate (ANIT) (0.025%), or control diet (AIN‐93M) for four weeks. Consistent with our hypothesis, PAR‐4 deficiency significantly increased portal inflammation and peribiliary fibrosis in mice fed ANIT diet, but did not increase liver necrosis. Hepatocellular necrosis increased significantly in FibγΔ5 mice fed ANIT diet compared to WT mice. The enhanced necrosis was accompanied increased hepatic deposition of type 1 collagen protein. The results indicate that PAR‐4 dependent platelet activation and fibrin‐αIIBβ3 integrin engagement have hepatoprotective effects in a model of chronic biliary injury.
Alveolar macrophages mediate release of mtDNA damage‐associated molecular patterns in Pseudomonas aeruginosa‐challenged rat lungs (145.6)
Authors: Kuck Jamie , Obiako Boniface , Pastukh Viktor , Gillespie Mark
Published: June 2021

Oxidative mitochondrial DNA (mtDNA) damage and release of mtDNA damage‐associated molecular patterns (mtDNA DAMPs) may contribute to bacteria‐induced lung injury. The cellular mechanism by which bacteria trigger mtDNA DAMP formation is unknown. We tested whether P. aeruginosa causes alveolar macrophage‐dependent release of mtDNA DAMPs and attendant degradation of alveolar‐capillary barrier function. To deplete alveolar macrophages, rats were given an intratracheal injection of liposome‐encapsulated clodronate or liposomes alone 24 hours prior to experiments. Lungs isolated, mechanically ventilated, and buffer‐perfused were challenged with intratracheal instillation of P. aeruginosa (Strain 103). The vascular filtration coefficient was measured 15 min after challenge. Amplification of 200 bp sequences via RT‐PCR was used to measure accumulation of mtDNA DAMPs or bacterial DNA in perfusion medium. Rat lungs treated with vehicle had increased permeability, whereas those treated with clodronate showed no increases in the vascular filtration coefficient or accumulation of mtDNA DAMPs in perfusate 15 minutes after PA103 challenge. These observations suggest that alveolar macrophages are critical for P. aeruginosa‐induced formation and release of mtDNA DAMPs into the pulmonary circulation and attendant changes in lung endothelial permeability.

Grant Funding Source: Supported by NIH
Defective CD40‐dependent antigen cross‐priming of CD8+ T cells in mice with conditional deletion of NF‐κB‐inducing kinase (146.11)
Authors: Katakam Anand , Brightbill Hans , Franci Christian , Wu Lawren , Mellman Ira , Delamarre Lelia , Austin Cary
Published: June 2021

Dendritic cells (DCs) link innate and adaptive immunity, using a host of innate immune and inflammatory receptors to respond to pathogens and inflammatory stimuli. While canonical NF‐κB signaling within DCs is clearly important for many of these responses, the role of non‐canonical NF‐κB signaling via the serine/threonine kinase NIK needs clarification. To investigate the function of NIK in DC stimulus responses and immunity, we generated transgenic mice with targeted NIK deletion in CD11c+ DCs. We observe that conditional deletion of NIK impairs CD40‐dependent cross‐priming of naïve CD8 T cells in vivo and deficient CD40‐stimulated antigen cross‐presentation and IL‐12p40 secretion by splenic‐derived DCs in vitro. In human monocyte‐derived DCs after siRNA silencing of NIK in vitro, we observe a similar IL‐12p40 secretion defect. These findings suggest that NIK serves to transmit a ‘DC licensing’ signal from CD4 T helper cells to naïve CD8 T cells during antigen cross‐priming of a CD8 T cell response.
Adverse cardiac remodeling mediated by the altered expression of versican (15.7)
Authors: Mjaatvedt Corey , Burns Tara , Escobar Patricia , Ansarizadeh Yosef , Le Saux Claude
Published: June 2021

Adverse remodeling following myocardial infarction (MI) is the primary pathologic process that leads to heart failure. The process is driven by normal repair mechanisms that become uncontrolled. This research focuses on the functional significance of the extracellular matrix molecule versican (Vcan) in regulating adverse remodeling and the deposition of insoluble fibrillar collagen outside of the infarct border zone. Our hypothesis is that adverse remodeling is mediated by an aberrant increase in Vcan deposition that promotes an increased presence of fibrocytes, cells expressing myeloid origin CD45+ and Hsp47+, into the injured as well as non‐inured myocardium. To test this hypothesis, we have experimentally induced MI by coronary ligation and compared WT, Vcan deficient (Vcan(tim1Zim)) and Cav1 null (a model of adverse remodeling) mice for expression of Vcan and the presence of fibrocytes within the injured and non‐injured myocardium. We show that in the WT Vcan is up regulated as part of the normal repair at the infarct borders. This expression pattern is accompanied by an increased infiltration of CD45+ cells within the Vcan rich boarder zone. Interestingly, in the Vcan depletion model, we measured significant reduced average injured wall thickness (247 vs. 394 µm), less infiltration of fibrocytes and an unexpected reduction of collagen deposition. In Cav1 null mice, Vcan is up regulated leading to a more widespread distribution of fibrocytes, associated with adverse remodeling after MI. A better understanding of adverse remodeling after MI will contribute to the development of extracellular matrix based interventions designed to reduce or prevent the morbid effects of post‐infarction remodeling.

Grant Funding Source: NHLBI R01HL66231 (CHM), Janey Briscoe Center for Excellence in Cardiovascular Research (CJLS)
Effects of tourniquet use on muscle cells during total knee arthroplasty (151.11)
Authors: Wu Brian , Hocker Austin , Gilbert Paul , Yi Anthony , Rao Ravi , Damodar Dhanur , Hatch George , Schroeder E. , Dreyer Hans
Published: June 2021

Skeletal muscle atrophy occurs at a rate of approximately 1% per day within the first 2 weeks following total knee arthroplasty (TKA). We have previously shown that signaling pathways regulating translation initiation are downregulated while catabolic pathways are up regulated while stress‐activated protein kinases (JNK) and all three arms of the endoplasmic‐reticulum stress pathway are activated. While we have attributed these alterations to tourniquet use during surgery causing ischemia‐reperfusion injury, definitive studies demonstrating cause and effect have not been performed. In order to investigate the differences in muscle cells based on tourniquet use, 36 men and women (15 males, 21 females, avg age=67.8 yrs) who underwent TKA were randomized to receive tourniquet, no tourniquet, or tourniquet during cementing only. Muscle biopsies were obtained before and after TKA from the vastus lateralis muscle. Preliminary results suggest upregulation of cleaved caspase 3 with tourniquet vs. no‐tourniquet. Further analysis is needed in order to determine the effects of tourniquet use on muscle cell stress pathways during TKA.
Excess endoplasmic reticulum is degraded by p62‐mediated selective autophagy in mammals (151.6)
Authors: Ding Wen‐Xing , Yang Hua , Ni Hong‐Min
Published: June 2021

Liver is the most vital and dynamic organ, and is the major site for the metabolism and detoxification of xenobiotics. The cytochrome P450 enzymes (CYPs), which are synthesized and localized in the endoplasmic reticulum (ER), are the most important enzymes responsible for the drug metabolism in the liver. It is known that there is increased ER proliferation and induction of CYPs to meet the needs of metabolism in response to several xenobiotics. Whether autophagy is essential for the removal of excess ER following xenobiotic‐induced ER proliferation and induction of CYPs, and whether an autophagy receptor is involved in this selective process in mammals remains elusive. In the present study, using GFP‐LC3 transgenic and liver‐specific Atg5 knockout mice, we show that autophagy is essential for the removal of excess ER after treatment with the hepatic mitogen TCPOBOP (t1, 4‐bis [2‐(3, 5‐dichloropyridyloxy)] benzene). In addition to regulating ER degradation, our results also suggest that autophagy plays a role in regulating the homeostasis of hepatic CYPs. Furthermore, we also show that p62/SQSTM1, an autophagy receptor that has been shown to be involved in many selective types of autophagy, may act as an autophagy receptor for selective erphagy. Taken together, our results indicate that autophagy is essential for selective removal of excess ER and hepatic CYP enzymes in mouse livers.

Grant Funding Source: Supported by NIAAA R01 AA020518; 5P20RR021940‐07; 8 P20 GM103549‐07