bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of PIKfyve in the Neutrophil Innate Immune Response
Authors: Winkler Michael , Dayam Roya , Choy Christopher , Sun Chun‐Xiang , Botelho Roberto , Glogauer Michael
Published: June 2021

Phosphoinositides are lipid signals that help control leukocyte function including phagocytosis, phagosome maturation and chemotaxis. For example, phosphatidylinositol‐3,5‐bisphosphate (PtdIns(3,5)P2), a lysosomal phosphoinositide, was recently shown to control phagosome maturation in macrophages. Here, we investigated the role of PtdIns(3,5)P2 in neutrophils. Neutrophils are the most abundant leukocyte and the first leukocyte involved in cell‐mediated immunity because of their proficiency in chemotaxis. Once at a site of infection, neutrophils release bactericidal molecules by degranulation, production of reactive oxygen species and phagocytosis of pathogens. Here, we pre‐treated neutrophils with apilimod, an inhibitor of PIKfyve, the kinase that synthesizes PtdIns(3,5)P2 and examined the effects on neutrophils. Overall, we observed that PIKfyve loss of function was highly detrimental to neutrophils. First, apilimod‐treated neutrophils led to lysosome‐vacuoation but not granule‐vacuolation. Second, PIKfyve inhibited cells showed reduced cell velocity and directionality towards an fMLP‐gradient. Third, apilimod treated cells showed an ~80% decrease in its phagocytosis of bacteria and a 75% decrease in phagosomes stained for lysosome markers. Lastly, neutrophils treated with apilimod showed a ~50% decrease in the production of superoxide, a reactive oxygen species produced by respiratory burst to kill bacteria. Currently, we are testing whether PIKfyve activity is necessary for activation of the Rac GTPase, which is essential for the above neutrophil functions. Indeed, preliminary results show that PIKfyve inhibited cells have reduced levels of Rac‐GTP bound.
Cross‐talk between the Growth Factor and Estrogen Signaling Pathways in Control of Breast Cancer
Authors: Applebaum Kayla , Holz Marina
Published: June 2021

The specific hypothesis underlying our proposed research is that positive crosstalk between the growth factor and estrogen signaling pathways is the basis of the growth advantage of Estrogen Receptor (ER)‐positive breast cancer cells, and is the driving mechanism for ligand‐independent ER activation and endocrine therapy escape. First, we have observed that in ER‐positive breast cancer cells the expression of the gene RPS6KB1, encoding S6K1, is regulated by estrogen/ER. While many studies have addressed the regulation of S6K1 kinase activity, very little is known regarding the transcriptional regulation of S6K1 expression. We determined that ER cooperates with other transcription factors, including GATA‐3 and ERRα in regulating expression of the S6K1 gene. Second, it has been shown that ER phosphorylated as a consequence of growth factor signaling is a strong marker of endocrine treatment response. Phosphorylation is important for ER transactivational activity, and ligand‐independent phosphorylation of this site may be involved in development of endocrine resistance in vivo. While several kinases have been implicated in phosphorylation of ER, the exact mechanism of these events is unclear. We characterize the contribution of mTORC1 to phosphorylation of ER, its effect on transcriptional activity of ER, and the role in endocrine resistance.
Structure/Function Characterization of S100B Inhibitors at Sites 2/3 within Malignant Melanoma
Authors: Cavalier Michael , Wilder Paul , Charpentier Thomas , Weber David
Published: June 2021

S100B is not merely a prognostic indicator within Malignant Melanoma (MM), but it promotes the degradation of p53 through a calcium‐dependent protein‐protein interaction. It is also now known that small molecule inhibitors of S100B (known as SBiXs) and RNA interference of S100B expression restore both p53 protein levels and normal transcriptional activation/apoptosis activities in MM, which typically has wild‐type p53. For these reasons, we aim to specifically inhibit the S100B‐p53 interaction as a potential therapy for MM. Our efforts at probing the binding surface of S100B revealed three persistent binding sites (Sites 1, 2, and 3), and efforts to discover/synthesize SBiXs which simultaneously bind all three sites are underway. Using a combination of structural biology techniques (X‐ray crystallography and NMR), in vitro binding, and cellular assays, the structure/function characterization of SBiXs binding Sites 2 and 3 were investigated. The SBiXs, which exhibit dissociation constants ranging from 40 nM to 100 μM, are compared and their ability to be extended into Site 1 are discussed. Such inhibitors may also have therapeutic value as early stage lead compounds for treating other cancers such as astrocytoma, renal tumors, and some forms of leukemia that also have elevated S100B.
Resveratrol and Radiation: Cytotoxicity and Cell Cycle Analysis
Authors: Gillard Mitchell , Upham Kent , Pogozelski Wendy , O'Donnell Robert
Published: June 2021

The primary purpose of our experiments was to determine if resveratrol, a polyphenolic compound found in different fruits, most notably the skins of red grapes, could enhance the killing of tumor cells treated with radiation. Using the melanoma‐derived MDA‐MB 435 cell line, cytotoxicity experiments were conducted to test the effects of these treatments both combined and individually on the cell line. Combination of both treatments exhibited additive effects on the amount of killing of these cells. To determine the mechanism by which this was occurring, analysis of the cell cycle was conducted using flow cytometry. Radiation (2Gy) and resveratrol (0.0135mg/ml) were shown to arrest the cells in the G2 and S phases of the cell cycle, respectively. Combination of these two treatments showed additive effects, arresting a greater percentage of cells in both the S and G2 phases of the cell cycle. A sub‐G­1 peak was also observed, suggesting some cells undergoing apoptosis. The Annexin Apoptosis Assay has shown conflicting resultssince cells treated with radiation and resveratrol have shown less apoptosis than cells treated with radiation alone. Further experiments using reverse transcriptase quantitative PCR were conducted to determine if select tumor suppressor (p53, Rb) and oncogenes (Myc and Bcl‐2) vary in levels among the treated cells. Upregulation of Bcl‐2, Rb1 and p53 was observed in cells treated with resveratrol alone and in cells treated with both resveratrol and radiation, perhaps protecting them from apoptosis. Our ongoing experiments will provide further insight to the mechanism by which cell death is occurring and explain the changes in the cell cycle.
Cancer Immunotherapy via Regulation of the Ubiquitin Proteasome Pathway
Authors: Kumar Suresh , Wu Jian , LaRocque James , Agarwal Saket , Marblestone Jeffrey , Kodrasov Matthew , Weinstock Joseph , Mattern Michael
Published: June 2021

Immune evasion is a hallmark feature of tumors as they employ various strategies to suppress the immune system's ability to recognize and destroy cancer cells. Significant advances in the understanding of the mechanisms of cancer immune evasion have led to the successful development of immunotherapies that exhibit clinical efficacy against hematological as well as solid tumors. These include monoclonal antibodies, allogeneic hematopoietic stem cell transplantation, vaccination, cytokines, T cell checkpoint blockade, and adoptive transfer of engineered T cells. Due to the underlying complexity of cancer immune evasion, however, several different approaches will likely be necessary for effective therapeutic management. We are taking a dual targeting approach, focused on the ubiquitin proteasome pathway, to develop novel small molecule cancer immunotherapeutics. We have identified inhibitors of a deubiquitylase (DUB) that is highly expressed in regulatory T (Tregs) cells and plays a critical role in promoting Treg functions. In addition, we have identified inhibitors of an E3 ubiquitin ligase that negatively regulates T‐effector cell function. These inhibitors are expected to suppress Treg functions and promote T‐effector activities. A combination of such inhibitors should provide powerful anti‐cancer immunotherapy.
Angiotensin‐(1‐7) as an Antinociceptive Agent in Cancer‐Induced Bone Pain
Authors: Forte Brittany , Slosky Lauren , Staatz William , Largent‐Milnes Tally , Vanderah Todd
Published: June 2021

Many cancerous solid tumors, including breast, metastasize to the bone and induce pain (CIBP). CIBP is often severe due to an enhanced inflammation in the bone, rapid bone degradation, and nociceptor sprouting. Opioids are often prescribed to manage this pain but may lead to enhanced bone loss and analgesic tolerance, compromising patient quality of life. Angiotensin‐(1‐7) (Ang1‐7), a product of Angiotensin II degradation, binds and activates the Mas receptor, a Gq/11‐protein coupled receptor (MasR). MasR activation after acute tissue insult results in diminished production of reactive species and further inflammatory response, yet no studies have investigated whether Ang1‐7/MasR play a role in CIBP. Therefore, we hypothesized Ang1‐7 acts via the MasR to inhibit CIBP by reducing proinflammatory cytokines and slowing bone loss in a murine model of breast CIBP. Cancer inoculation of the femur increased spontaneous and evoked pain behaviors that were significantly reduced after Ang1‐7 administration (p<0.01); co‐administration of a MasR antagonist reversed this reduction. Cytokine/chemokine profiles of femur extrudates from Ang1‐7 mice revealed significant increases in the relative expression of C5/C5a, IL‐1ra, IL‐16, M‐CSF, MIG, and decrease in the expression of MIP‐1α compared to vehicle controls (p<0.05). Although Ang1‐7 intervention changed the composition of inflammatory mediators in the bone‐tumor microenvironment, bone degradation was not impacted. Nearly 70% of advanced stage cancer patients experience excruciating pain that may be exacerbated by available analgesics, while data here suggests modifying the cancer‐induced inflammatory response in the bone microenvironment with Ang1‐7 via MasR significantly attenuates CIBP. Studies funded by the Department of Pharmacology at the University of Arizona.
Vascular Disrupting Activity of OXi8006 in Endothelial Cells and Its Phosphate Prodrug OXi8007 in Breast Tumor Xenografts in Vivo
Authors: Odutola Samuel , Strecker Tracy , Cooper Morgan , Tidmore Justin , Charlton‐Sevcik Amanda , MacDonough Matthew , Hadimani Mallinath , Ghatak Anjan , Lopez Ramona , Li Li , Liu Li , Mason Ralph , Chaplin David , Pinney Kevin , Trawick Mary Lynn
Published: June 2021

Tubulin‐binding, small‐molecule vascular disrupting agents (VDAs) are anticancer agents that rapidly depolymerize microtubules, and cause a pronounced shutdown in blood flow to solid tumors while leaving the blood flow in normal tissues intact. The indole‐based tubulin‐binding compound OXi8006 and its phosphate prodrug OXi8007 were investigated as VDAs. OXi8006 and OXi8007 were cytotoxic towards rapidly proliferating human umbilical vein endothelial cells (HUVECs), and disrupted tubular networks of HUVECs. OXi8006 and OXi8007 also disrupted microtubules, caused cell cycle blockade at G2/M, and extensive reorganization of the cytoskeletal network in activated HUVECs. The mechanism of action involved an increase in focal adhesion formation associated with an increased phosphorylation of both non‐muscle myosin light chain and focal adhesion kinase. These effects were diminished by an inhibitor of RhoA kinase, a downstream effector of RhoA. OXi8007 caused potent dose‐dependent antivascular activity assessed by bioluminescence imaging in an MDA‐MB‐231‐luc breast cancer xenograft mouse model. These findings were confirmed by histology. The results demonstrated that OXi8006 and OXi8007 are potent VDAs. (This work was supported by the NIH NCI [Grant 5R01CA140674] and OXiGENE, Inc.)
Another Reason to Eat Your Broccoli: Naturally Occurring Isothiocyanates Inhibit Deubiquitinating Enzymes
Authors: Lawson Ann , Long Marcus , Qian Yu , Coffey Rory , Weerapana Eranthie , El Oualid Farid , Hedstrom Lizbeth
Published: June 2021

The chemoprotective effects of a diet rich in broccoli or kale has been appreciated for several decades. Such cruciferous vegetables are a rich source of isothiocyanates (ITCs) such as benzyl ITC (BITC) and phenethyl ITC (PEITC). Each of these ITCs have antiproliferative activity against various tumors and PEITC is in clinical trials for lung and oral cancers. However, the mechanism by which ITCs suppress carcinogenesis has been the subject of much debate and numerous potential targets have been proposed. Here we show that BITC and PEITC inhibit the deubiquitinating enzyme (DUB) USP9x in vitro and in living cells. Both ITC treatment and USP9x knockdown decrease the levels of the oncogenic proteins MCL1 and Bcr‐Abl kinase. BITC and PEITC also inhibit UCH37, a proteasome associated DUB involved in the degradation of many proteins. Competitive activity profiling in cells pre‐treated with these ITCs suggests that other DUBs may also be inhibited. Inhibition occurs at physiologically relevant concentrations and time scales, and thus can explain many of the anticancer properties of dietary ITCs.
Addressing Environmental Determinants of Food Insecurity in Rural Guatemalan Communities
Authors: Lee EunKyung , deFulladolsa Patricia , Sibrian Ricardo , Medina Maria , Bermudez Odilia
Published: June 2021

Objective

To assess prevalence of household food insecurity (F‐Ins) and factors related to solid waste (SW) exposure among residents of 3 communities from the municipality of Santa Catarina Mita, Department of Jutiapa, Guatemala.

Methods:

F‐Ins and SW were assessed by questionnaire and direct observation in 184 families from the communities of La Barranca (LB), El Quebracho (EQ) y La Javia (LJ). Descriptive statistics were generated to explain findings.

Results:

The 184 families included 590 members, mean # =4.4+2.3; 45% males and mean age=31y, range 0‐99y. Moderate F‐Ins was identified in 34%, 42% and 17% of families in LB, EQ y LJ, respectively. Severe F‐Ins was found, for the same communities, in 15%, 4% and 8% of them, respectively. For SW disposal, only LJ had a regular pick‐up collection truck. The other communities practiced intra‐household methods for SW disposal, mainly burning. When asked about level of concern burning their trash, 80% of total families said to be concerned with this practice. With crop waste, burning was the most used way for disposal at 19% in LJ, 71% in EQ and 55% in LB; while only 10%, 4% and 9% of families from same communities (same ordering) did composting of organic waste; while re‐using it (e.g. as animal feeds) was done in by 19% in LJ, 56% in EQ and 53% in LB, respectively.

Conclusions

Food insecurity affected large proportion of families in the communities of LB, EQ and LJ. Those families identified SW management as a major concern. The solid waste originated by families in this study may threaten foodsecurity and the environment as only few of those families were practicing environmental friendly strategies for SW management.
The Effectiveness of Two Ready to Use Supplementary Foods (RUSFs) Differing in Dairy Protein Content on Growth and Nutritional Status of Young Children: A Pilot Study in Preschools in Guinea‐Bissau
Authors: Schlossman Nina , Batra Payal , Balan Ela , Pruzensky William , Shae Kyla , Schleicher Molly , Urban Lorien , Saltzman Edward , Roberts Susan
Published: June 2021

A USDA‐funded cluster‐randomized controlled trial compared two RUSF containing 500 calories and either 15% or 33% of dietary protein from dairy for 3 months versus a wait‐listed control. Each RUSF was provided 5 days per week. Intention‐to‐treat analyses were conducted with changes in weight‐for‐age and height‐for‐age Z‐scores (WAZ, HAZ) as primary outcomes. Additional outcomes included mid‐upper arm circumference (MUAC), hemoglobin and retinol binding protein levels and disease incidence.

Z‐scores increased significantly in all groups over baseline (P=>0.01) but there was no significant effect of the RUSFs on changes in WAZ or HAZ. There was a significant effect of supplementation on the association between baseline WAZ and WAZ gain (P<0.002). There was a significant positive effect of randomization to the 33% RUSF on change in MUAC (P<0.05). There was a significant decrease in reported rates of malaria in children randomized to either supplement.

This study provides the first evidence that RUSF with 33% versus the more typical 15% of protein provided by dairy may have particular benefit for prevention of wasting. It also indicates that RUSFs demonstrate growth benefits across the range of baseline anthropometric measures. It further shows that preschools can be an effective platform for implementation of intensive programs for prevention of malnutrition in young children living in low‐income countries.
Women's Economic Autonomy, Education, and Experience of Domestic Violence Are Associated with Household Food Security among Pregnant Women in MINIMat Study in Bangladesh
Authors: Kulkarni Shibani , Frongillo Edward , Naved Ruchira , Ekström Eva‐Charlotte
Published: June 2021

Low food security is highly prevalent in Bangladesh. Pregnant women are especially vulnerable to the harmful effects of food insecurity on maternal and child health and nutrition. While socioeconomic status (SES) is a known determinant of food security, limited evidence is available on how women's economic autonomy, education, and experience of domestic violence are associated with food security. We aimed to quantify how these measures were associated with food security after accounting for SES. We used data from 3870 pregnant women from the Maternal and Infant Nutrition Intervention (MINIMat) study in Matlab, Bangladesh. We performed multiple linear regression analysis with full information maximum likelihood to account for missing data assumed to be missing at random on household food security scores that were based on a context‐specific questionnaire developed for Bangladesh. SES, women's age, education, lifetime experience of domestic violence, and household economic autonomy were significant determinants of household food security (p<0.05). One standard deviation (SD) higher SES, education, and economic autonomy corresponded to 0.46, 0.07, and 0.08 SD higher food security, respectively. One SD higher domestic violence score was associated with a 0.06 SD lower food security. These results suggest that empowering women can increase food security even if SES does not improve. Understanding how to empower women in their context is essential to designing effective food‐security interventions.
Comparison of International Dietary Guidelines and Food Guides in Twelve Countries across Stages of the Nutrition Transition
Authors: Mattei Josiemer , Gicevic Selma , Malik Vasanti , Aftosmes‐Tobio Alyssa , Spiegelman Donna , Willett Walter
Published: June 2021

Evaluating dietary guidelines from various countries can help identify their strengths and limitations, yet such assessments are lacking. This study aimed to qualitatively compare current population‐level dietary recommendations and pictorial food guides issued by government or nutrition agencies in 12 countries across nutrition transition stages (early, ongoing, transitioned) and the World Health Organization. The examined content included general and specific recommendations for consumption of foods or dietary practices within main categories of food groups, nutrients, or beverages; additional advice on lifestyle, nutritional, cooking, or eating habits; and specific food examples depicted in food guides. Food group categories varied considerably by country (especially for legumes), but general and serving‐specific recommendations were mostly consistent, except for servings of Cereals and Grains, and Alcohol. All countries included physical activity recommendations, as well as advice pertinent to their culture or needs within nutrition transition stage. Food guides were generally plate‐ or pyramid‐shaped, and depicted culturally‐appropriate healthy options but also unfavorable foods. Recommended proportions of macronutrients or food groups were largely for carbohydrates or cereals/grains and vegetables. In summary, international dietary guidelines across nutrition transition stages are consistent and generally health‐promoting, but they could be strengthened with additional evidence‐based food depictions and advice on beneficial dietary and eating habits.
Urbanization, Markets, and Malnutrition in Rural Farm Households
Authors: Darrouzet‐Nardi Amelia
Published: June 2021

Agricultural productivity growth accelerates urbanization by supplying food and labor to urban areas. Towns and cities may also grow for separate reasons, pulling food and resources out of rural areas. Whether pushed or pulled, urbanization and market development creates new opportunities for rural agricultural households. This study tests whether household proximity to more established towns and cities has improved or worsened malnutrition among over 400,000 children and their mothers across 43,850 survey clusters in 46 low‐ and middle‐income countries between 1986 and 2011. Using an extensive database of 83 Demographic and Health Surveys combined with geographic and national accounts data, I examine the relationship between urbanization and nutrition in rural farm households using non‐parametric and instrumental variables methods, while controlling for region and birth cohort fixed‐effects. I find that rural children living in areas with a longer history of urbanization are heavier and taller at a wide range of income levels. I also find heavier mothers in rural farm households where urbanization has continued the longest. The prevalence of stunting and wasting among rural farm children is negatively associated with nearby urbanization, and the prevalence of child and maternal overweight in rural farm families is positively associated with nearby urbanization. Results suggest that access to urban markets has improved rural child heights and weights, and potentially increased the risks of overweight and obesity later in life. These findings indicate that there is ample opportunity to guide market development in ways that promote improved nutrition while limiting the rise of diet‐related disease. This study was supported by a U.S. Borlaug Fellowship in Global Food Security.
Food Frequency consumption and Food‐Related Habits among Brazilian students
Authors: Woolley Natalia
Published: June 2021

Objective

To study associations between frequency of eating healthy/unhealthy foods, and food‐related habits among Brazilian adolescent students.

Methods

The Pesquisa Nacional de Saude do Escolar (PENSE), a national survey conducted every three years by the Brazilian Institute of Geography and Statistics (IBGE), assesses health related habits among young adolescents. It was modeled after the Global School‐Based Student Health Survey and the Youth Risk Behavior Surveillance System.

The 2012 survey included 109,104 students from 2,842 schools, obtained using multi‐cluster sampling. Food consumption was assessed using questions about consumption of selected foods (e.g. beans, candy) over the previous week, and regular consumption was defined as eating a food item five or more days. Food‐related habits included eating lunch/dinner with parents and having breakfast. The study was conducted using SAS 9.3 and Chi Square statistical tests were used to analyze categorical data. IBGE's descriptive statistics were also used.

Characteristics of the student population were summarized by estimating frequency distributions (categorical variables). Around 47.8% of students were male and 52.2% female.

Preliminary Results

Frequency of eating beans (healthy food) regularly was higher for boys (p‐value <0.001, Cramer's V= 0.11); 74.6% ate beans regularly compared to 65.6% of girls. Girls had higher frequency of eating candy (unhealthy food) (p‐value <0.001, Cramer's V= 0.16); 48% ate candy regularly compared to 34% of boys. Consumption of milk (healthy food) was also higher for those who ate breakfast; 59% of students who ate breakfast regularly also drank milk regularly (p‐value< 0.001, Cramer's V=0.11). Multivariate analysis will be used to evaluate these associations by considering the effects of potential confounders.
An Atole Fortified with 21 Vitamins and Minerals Improves Nutritional Status of 6 to 72 Month‐Old Children in 6 Nurseries in Guatemala City
Authors: Villanueva Lisa , Palacios Ana , Cuy Castellanos Diana , Reinhart Gregory
Published: June 2021

Chispuditos® is a corn/soy atole fortified with 21 vitamins and minerals designed to reduce micronutrient deficiency of Central American children. A portion of atole (18.75g) was provided for 5 days/week to 6‐72 month‐old children. Seven hundred and forty seven children completed 1 year of the nutritional intervention. Hemoglobin, anthropometry and incidence of respiratory tract infections and diarrhea were analyzed at baseline, six months and one year. Repeated measures ANOVA indicated an increase in hemoglobin from baseline=11.76±1.17g/dL to endline=12.39±1.05 g/dL, p<0.001. HAZ scores increased from ‐1.25±1.02 to ‐1.07±0.96, p<0.001 over the time course of the intervention. Furthermore, there was a 57.1% reduction in respiratory tract infections, p<0.001 after 12 months. No changes in the incidence of diarrhea from baseline to one year were observed. Overall, children in this study had an improvement in HAZ scores, hemoglobin concentrations and respiratory tract infections after 12 months of intervention, while previous studies in comparable settings took approximately 24 months for HAZ scores to improve.

Funded by The Mathile Institute for the Advancement of Human Nutrition.
Vitamin A Deficiency and Mother‐Infant Correlations in Bolivia
Authors: Cattran Alexander , Burke Rachel , Lipus Adam , Revollo Rita , Iñiguez Volga , Leon Juan , Suchdev Parminder
Published: June 2021

Vitamin A deficiency (VAD) affects an estimated one‐third of preschool‐aged children in developing countries and is an important contributor to global child mortality. The goal of this analysis was to identify risk factors of VAD in a cohort of Bolivian infants. Healthy infants (n=163) were recruited from 2 hospitals in El Alto, Bolivia, and followed from 1 to 6 months of age. Blood specimens taken at 6 months were analyzed for retinol‐binding protein (RBP) levels (VAD defined as RBP < 0.7 µmol/L), C‐Reactive Protein (CRP), and alpha(1)‐acid glycoprotein (AGP). Potential covariates in logistic regression models of VAD included infant gender, stunting (length‐for‐age Z score < ‐2), iron deficiency (ferritin< 12 μg/L), acute respiratory or diarrheal illness, breastfeeding, maternal age, maternal vitamin A supplementation, maternal employment, and access to private toilets. Elevated CRP (>5 mg/L) and AGP (>1 g/L) were included in all models to account for inflammation. Prevalence of VAD was 25%. Backwards elimination indicated maternal age (OR: 4.6, 90% CI: [1.8‐11.4] for 25‐30 vs. 20‐25 years), maternal employment (0.4 [0.2‐0.9]) and elevated CRP (3.1 [1.2‐7.9]) were significantly associated with VAD using an alpha of 10%. These results suggest that sociodemographics may be an important risk factor for VAD, while inflammation also affects measures of VAD. A limitation of this study is the small sample size and subsequent lack of power, which will be improved as data collection continues.
The Message Environment and Salience of Infant and Young Child Feeding Messages for Health Workers, HIV‐infected and HIV‐uninfected Mothers in Urban Haiti
Authors: Fox Elizabeth , Pelto Gretel , Rouzier Vanessa , Debrosse Marie Guerda , Rasmussen Kathleen , Young Sera , Strupp Barbara , Pape Jean William , Pelletier David
Published: June 2021

Worldwide, mothers with young children receive many infant and young child feeding (IYCF) messages. Some of these messages are health provider generated, while others are culturally influenced and community generated. We aimed to determine the scope, content and salience of these messages in urban Haiti. We applied the qualitative method of “free listing” with 13 health workers (HW), and 15 HIV‐infected and 15 uninfected mothers with infants 0‐6 months old at GHESKIO. Participants were asked to list all messages women receive about IYCF, and specifically HIV and IYCF. Message salience was determined by message frequency and rank order using FLAME 1.1, and messages were coded for key themes using NVivo 10. For all groups, WHO IYCF recommendations were highly salient, but community‐based messages were also highly salient for mothers. Maternal‐centered messages were more salient for mothers than for HW, who focused on infant‐centered messages. In addition, HW and HIV‐uninfected women identified a wider range of breastfeeding benefits compared to HIV‐infected women who focused primarily on the health of their infants. As many salient messages are community generated and differences exist between HIV‐infected and uninfected women, we conclude that IYCF messages provided to women should be more sensitive to the broader message environment and the consequences of these messages for mothers' breastfeeding behaviors.
Are complementary foods provided to 6‐24 months old children meeting the World Health Organization (WHO) guidelines? Demographic and Health Survey (DHS) data from four countries
Authors: Marriott Bernadette , Nasarre Patrick , Lee FuShing , Poole Ann , Wallingford John
Published: June 2021

WHO recommends provision of complementary foods with sufficient diversity across seven food groups and iron‐rich foods to meet nutritional needs that also are measured by four solid food feeding indicators (FI). Earlier studies have reported positive associations between meeting the FI and economic status or maternal education. We assessed complementary feeding practices among children 6‐24 months of age using comparable DHS data and the WHO FI among four countries of dissimilar economic status: Egypt, Indonesia, Philippines, and Cameroon (GDP= 6,600; 5,200; 4,700; 2,400 USD/capita, respectively). Significant differences existed among the countries in meeting the FI, consuming the WHO food groups, and reported intake of specific fortified foods such as baby cereal (all p<0.01). Percent of children meeting the WHO guidelines did not parallel GDP. Cameroon had significantly fewer children meeting all four of the solid food FI (p<0.01) than the other countries, yet children in Cameroon were significantly more likely to be fed with meat, vitamin A rich foods, and fruits than children in Egypt (p<0.01). While Philippines had a lower GDP than Egypt and Indonesia, it had a higher percentage of children meeting all four FI's (p<0.01) and mothers completing secondary school or higher education. Among these four countries, maternal educational achievement appears to be a better predictor of complementary feeding practices than country GDP. Research Support: Nutrispectives, Inc.
Transcriptional regulation by nuclear phosphoinositides
Authors: Stijf‐Bultsma Yvette , Sommer Lilly , Tauber Maria , Giardoglou Panagiota , Jones David , Gelato Kathy , Baalbaki Mai , Hart Daniel , Lauberth Shannon , Haramis Anna‐Pavlina , Fischle Wolfgang , Divecha Nullin
Published: June 2021

Phosphoinositides are a family of seven lipids that are present in various subcellular compartments at low levels, compared to other phospholipids. Their levels are regulated by an array of kinases and phosphatases that respond to extrinsic and intrinsic signals in order to change the phosphoinositide profile in different compartments. For example in the nucleus the phosphoinositide PtdIns5P is phosphorylated by the lipid kinase PIP4K2B to generate PtdIns(4,5)P2. In response to activation of stress pathways, PIP4K2B becomes phosphorylated and less active and this in part leads to an increase in nuclear PtdIns5P. Changes in nuclear PtdIns5P are sensed by nuclear proteins that contain lipid interaction motifs which act to transduce the changes in the level of nuclear PI into changes in functional output. PIP4K2B is present in muscle tissue and in myoblasts and we have investigated how its expression regulates myogenic differentiation. Using C2C12 cells as a model of myogenesis we have identified a pathway that illustrates how signalling through PIP4K2B/PtdIns5P can directly regulate gene transcription. Further characterisation of nuclear proteins that can interact with phosphoinositides suggest that changes in nuclear PI are likely to impact on many aspect of chromatin regulation and eventually on transcriptional output.
Hedgehogs and Lipids
Authors: Salic Adrian
Published: June 2021

The Hedgehog pathway plays critical roles in metazoan development and in cancer. In vertebrates, Hedgehog signaling initiated in primary cilia activates the seven‐spanner membrane protein Smoothened, and leads to activation of Gli proteins, which control the transcriptional output of the pathway. I will discuss our recent findings on the mechanism by which Smoothened is activated by oxysterols, a mysterious class cholesterol metabolites with potent biological effects. Our results elucidate important aspects of Hedgehog signal transduction in vertebrates, and suggest novel strategies for blocking oncogenic Hedgehog signaling.
Aluminum and other metal content of oral pediatric medications
Authors: Yokel Robert , Seger Sarah , Unrine Jason
Published: June 2021

The objective was to determine the concentrations of aluminum and other potentially toxic metals in representative common oral medications administered to healthy American infants and to evaluate if toxic levels might be administered with normal use. An oral rehydration solution, nine non‐prescription medications, and four prescription medications were prepared for determination of Al, Cd, Cr, Co, Cu, Pb, Mg, Mn, Se, Ag, Sr, U, V, and Zn by ICP‐MS. The amount of toxic metals in the maximum recommended dose for one week's administration of each pharmaceutical was calculated and compared to reported tolerable upper intake levels or permissible weekly exposures. Calculations were based on a 7.6 kg infant, average for a 6 month old. Al was < 1% of the Joint Food and Agriculture Organization of the UN/WHO provisional tolerable weekly intake. Cd was < 2.5%, Cu and Pb < 5%, and V < 1% (except for the rehydration solution [~ 11%]) of the United States Pharmacopeia permissible daily exposure in all samples. Sr was < 1% of the EPA oral reference dose for toxicity. Ag was below the limit of detection in most samples. An ultratrace amount of U was detected in only one product. No products provided > 5% of the recommended weekly allowance of Mg or > 25% of Se, or > 25% of the tolerable upper limit of Mn. Some products provided > 100% of the adequate intake of Cr. No concerns for metal toxicity were uncovered in these results. Supported by The Pharmaceutical Sciences Department and Office of the Dean, College of Pharmacy, University of Kentucky.
No Long Term Effect of Soy Infant Formula on Reproductive Organs Size at Age 5 Years
Authors: Andres Aline , Moore Mary , Linam Leann , Casey Patrick , Cleves Mario , Badger Thomas
Published: June 2021

Several published reports suggest that phytochemicals, such as isoflavones found in soybeans, impair reproductive function in animals and raise the possibility that consuming soy infant formula could alter estrogen‐sensitive organ development in children. This study compared reproductive organs volumes and morphological characteristics in 101 children aged 5 years who were breast fed (N=35, 18 F, 17 M), milk formula fed (N=32, 18 F, 14 M) or soy formula fed (N=34, 15 F, 19 M) as infants. Breast buds, uterus, ovaries, prostate, and testicular volumes and characteristics were assessed by ultrasonography. Birth weight, birth length, gestational age, age at examination or weight and height at age 5 years did not differ between diet groups (P>0.05). Among girls, there were no significant differences in breast bud, ovarian or uterine volumes, counts of ovaries with cysts, ovarian cysts numbers, ovarian cysts size and uterine shape between diet group adjusting for race, gestational age, birth weight, birth length, child's age, weight and height. Among boys, there were no significant differences in breast bud, testes or prostate volumes or morphological characteristics between diet groups after adjusting for covariates. These data suggest that soy formula does not adversely affect reproductive organs volumes and morphological characteristics in children at age 5 years. The follow up of these children through puberty should help delineate potential early infant feeding effects on reproductive function later in life. Funded by USDA‐ARS CRIS # 6251‐51000‐005‐03S.
Suburban and Rural Women: Internationally the most Vulnerable to Food Insecurity
Authors: Dallmann Diana , Melgar Quinonez Hugo , Ballard Terri
Published: June 2021

People in rural (Ru) and impoverished suburban areas (Sb), as well as women, have higher rates of food insecurity (FI) when compared to other populations. This has been reported when applying different FI measurement tools in diverse settings. In this study FI was assessed using the Food Insecurity Experience Scale (FIES) as part of the 2014 Gallup World Poll (GWP). The objective was to determine differences in FI by gender and area of residence using the same measurement tool (FIES) as applied by GWP in individuals of 42 countries in diverse settings. Differential Item Functioning (DIF) was previously assessed using Rasch model. No significant DIF for any of the 8 items in FIES was detected between men and women (DIF 蠄 0.25 logit), or between individuals in four settings (Ru, Sb, small towns (St) and large cities (Lc)) (DIF 蠄 0.40 logit). Men living in Lc showed the lowest prevalence of FI when compared to men and women living in the other settings. Multivariate logistic regression analysis showed that women of Sb, Ru, St, and Lc had significantly higher odds ratios for FI (OR: 1.74, 1.70, 1.28, 1.14, respectively) when compared to men in Lc. Additionally, men in Sb, Ru and St, had also significantly higher ORs for FI (1.57, 1.47, 1.28, respectively) when compared to their male peers in Lc. This analysis was adjusted by country of residence, level of education, income, age, household size and marital status. The results highlight the importance of developing and carrying out interventions that incorporate the challenges faced by individuals belonging to diverse populations. Global gender disparities related to FI must be considered by policy makers and practitioners in order to more effectively address this phenomenon.
Determinants of Young Children's Sleep Duration in the U.S. Affiliated Pacific: The Children's Healthy Living Program
Authors: Li Fenfang , Novotny Rachel , Fialkowski Marie , Wilkens Lynne , McGlone Katalina , Uchima Margaret , Nelson Randall , Bersamin Andrea , Vargo Agnes
Published: June 2021

Sleep plays an important role in the health of young children and is associated with childhood obesity. This study reports sleep duration and its determinants in young children from five jurisdictions in the U.S. Affiliated Pacific (USAP) from the Children's Healthy Program (CHL).

Questions on children's demographic profile, sleep duration, and screen time were all adapted from previous studies and answered by parents/caregivers. The results reported include 3,894 children (2‐8 yo). Mean sleep duration was 9.6 hours (h) (sd=1.7). Twenty‐four percent of the children slept between 11‐13 hours daily, 66% slept between 8 to 10 hours and 10% slept less than 8 hours daily.

A linear regression model of sleep duration found the following significant predictors: child's sex, age, race, family income and geographical location. Mean sleep duration was higher by 0.13 h in girls than boys (p=0.03), by 0.58 h for 2‐5 year olds than 6‐8 year olds (p<.001), and by 0.38 h for children from families with an income of more than $35,000 than those with a lower income (p<.001). Compared to Whites, American Indians/Alaska Natives, Native Hawaiians/Pacific Islanders, and multiracial children had significantly lower mean sleep duration (p<.05). Children from American Samoa had the highest mean (10.2 h), while children from Guam had the lowest mean (9.2 h). There was a significant negative association between screen time and sleep (p<.001) and a non‐significant negative association between physical activity and sleep. Interventions targeting sleep duration among young children need to consider socio‐demographic and geographic differences.
The Association between Increased Economic Resources and Birth Weight Among Native Americans in California: A Natural Experiment
Authors: Jones‐Smith Jessica , Dow Will , Oddo Vanessa
Published: June 2021

Background

Native American‐owned casinos have been associated with increased economic resources and decreased risk for childhood overweight/obesity among Native Americans.

Objective

We test whether casinos are associated with large‐ for‐gestational age (LGA) (>90th percentile compared to sex‐and‐gestational‐age‐specific reference population values). Secondary analyses examined the relationship between casinos and excessive gestational weight gain and maternal pre‐pregnancy body mass index (BMI).

Methods

Data came from California birth records and included 23,237 births (between 1987 to 2011) to Native American women living near tribal lands. Casino presence and size was indicated by the number of slot machines per Native American living on tribal lands in each zip code in each year ('slots per capita'). Zip code‐fixed‐effects linear and linear probability regression models compared communities to themselves over time, before and after the opening/expansion of casinos, to estimate the relationships between casino openings/expansions and LGA, excessive gestational weight gain, and maternal BMI.

Results

Opening or expanding a casino was associated with a decreased risk of LGA (bslotspercapita = ‐0.0061 (95% CI: ‐0.0095, ‐0.0027); bslotspercapita_squared= 0.00009 (95% CI: 0.000037, 0.00015), and with lower maternal BMI (b= ‐0.12 (95%CI: ‐0.19, ‐0.04), but was not associated with excessive gestational weight gain (b= 0.001 (95%CI: ‐0.006, 0.008).

Conclusions

Economic resources from Native American casinos are associated with decreased risk for LGA and decreased maternal BMI among Native Americans.
Salivary biomarkers for chewing betel (areca) nut
Authors: Franke Adrian , Mendez Ana Joy , Lai Jennifer , Arat‐Cabading Celine , Li Xingnan , Custer Laurie
Published: June 2021

Objective

Betel nut (Areca catechu L.) chewing is carcinogenic to humans and strongly associated with oral cancer, especially in Guam. We identified chemicals specific for the 3 most commonly consumed betel nut preparations in Guam [mature nut (BN), mature nut+ betel leaf (BL), and betel quid (BQ) consisting of the young nut+betel leaf, lime and tobacco]; and identified salivary compounds extracted from betel chewers chewing these preparations to establish a salivary profile specific for BN, BL and BQ chewers.

Methods

15 betel chewers in Guam were randomized evenly to BN, BL or BQ. Betel material was extracted with PBS buffer. Saliva was precipitated with acetonitrile, diluted with formic acid and analyzed by LCMS. Saliva levels before and after chewing were compared by t‐tests; ANOVA compared differences between groups. p<0.05 indicated significance.

Results

Levels of arecoline and guvacine were highest in the young and mature BNs, respectively; chavibetol was found only in leaf extracts. Significant increases from before vs. after saliva levels were observed for guvacine (BN, BQ), arecoline (BN, BL, BQ), guvacoline (BN), arecaidine (BN, BL, BQ), nicotine (BQ), and chavibetol (BL, BQ). Pharmacokinetic parameters were also determined.

Conclusion

Our results suggest the presence of 1) areca alkaloids (arecoline, guvacine, and arecaidine), chavibetol, and tobacco‐specific alkaloids (nicotine, cotinine, hydroxycotinine, NNK, NNN and NAT) can identify BQ chewers; 2) areca alkaloids and chavibetol can identify BL chewers and 3) salivary areca alkaloids can identify BN chewers.

This research was supported by the NCI awards U54CA143727 and U54 CA143728
Relationship between Intake of Phylloquinone (Vitamin K1) with Blood Lipids and Biomarkers of Glucose Homeostasis in Haitian Americans and African Americans With and Without Type 2 Diabetes
Authors: Basiri Raedeh , Zarini Gustavo , Vaccaro Joan , Exebio Joel , Huffman Fatma
Published: June 2021

Background

Limited evidence suggests a beneficial role of vitamin K1 in blood lipids and glucose homeostasis; however, no study exists on the associations between phylloquinone intake with blood lipids and homeostatic model assessment (HOMA) in African Americans (AA) and Haitian Americans (HA).OBJECTIVE: To determine the relationship between dietary phylloquinone intake with blood lipids and biomarkers of glucose homeostasis in AA and HA with and without type 2 diabetes (T2D). METHODS: This cross sectional study recruited participants from community centers in South Florida. Dietary phylloquinone intake was estimated by using Willet's food frequency questionnaire. Blood lipids, glucose and insulin were measured in fasting states. HOMA‐2 was used to estimate beta cell function (HOMA2‐β), insulin sensitivity (HOMA2‐IS) and insulin resistance (HOMA2‐IR). Statistical analysis included t‐test, chi‐square and linear regression. RESULTS: 390 participants (234 without T2D and 156 with T2D) were included in the analysis. The mean age was 54 years and approximately half (53%) of the participants were female. Phylloquinone intake was associated with HDL‐cholesterol (B= 0.041, P=0.015) and triglycerides (B=‐0.001, P=0.041) in HA with T2D. Phylloquinone intake was not associated with HOMA2‐IR, HOMA2‐β, and HOMA2‐IS.

CONCLUSION

Findings of this study support a potential beneficial role for phylloquinone in blood lipids among HA men and women with T2D. Funding for this research was provided through an NIH/NIDDK sponsored grant.
Using the Delphi technique to establish a nutrient profiling system for pre‐packed food
Authors: Ma Ning , Zhang Geng , Wang Chunling
Published: June 2021

Objective

To establish a nutrient profiling system for pre‐packed food which contains nine groups of indicators aiming nine different kinds of pre‐packed foods with Delphi technique.

Methods

The frame structure of indicator system was established in a pre‐Delphi expert meeting. A 2‐round E‐mail‐administered Delphi process was conducted in a group of selected experts. The specialist authority coefficient and Kendall's coefficient of concordance W were calculated. The indicator system was revised based on statistical analysis and expert opinions.

Results

The response rates of Delphi round 1 and round 2 were 64.3% and 92.6%, respectively. The specialist authority coefficient Cr was 0.84.In round 1, Kendall's W of indicator weight in the 9 groups indicators were 0.381, 0.318, 0.422, 0.448, 0.580, 0.321, 0.310, 0.417, and 0.203, respectively (all P < 0.01). In round 2, Kendall's W of indicator weight in the 9 groups indicators were 0.737, 0.655, 0.697, 0.737, 0.778, 0.709, 0.702, 0.641, and 0.758, respectively (all P < 0.01). A pre‐packed food nutrient profiling system was built and it contains 11 first class indicators, 127 second class indicators.

Conclusions

Both the representativeness of experts and the specialist authorities are high. After two rounds consultations, expert consensus on indicator settings is formed. The indicator system built in this study is a fitting tool in pre‐packed foods nutrition value evaluation.