bluuebunny/crossref_metadata_2025 huggingface dataset:
Feeding of infant formula at birth links with feeding of infant formula and discontinuation of breastfeeding in Vietnam
Authors: Nguyen Tuan , Frongillo Edward , Hajeebhoy Nemat
Published: June 2021

Few studies have examined the association between feeding infant formula at birth and future feeding patterns. This study was conducted to examine the association between feeding infant formula in the first 3 days after birth (IF3d) and current feeding infant formula (IFcur), as well as discontinuation of breastfeeding (noBF). In a cross‐sectional survey, we interviewed 10,681 mothers with children aged 0−23.9 mo in Vietnam about current breastfeeding practices and feeding practices during 3 days after birth. The prevalence of feeding IF3d was 52%, higher in those with cesarean delivery (78%) than vaginal delivery (45%, P < 0.01). The prevalence of IFcur in children 0−0.9, 3−3.9, 4−8.9, and 9−23.9 mo fed with IF3d was 31%, 40%, 50% and 50%, which was statistically higher than those who were not fed IF3d (5%, 15%, 30%, and 40%, respectively). The stratified analysis by delivery mode showed a similar trend. At 12 to 14.9 mo, the noBF prevalence was higher in infants fed IF3d than who were not. IF3d was associated with increased prevalence of IFcur (OR: 1.76; 95% CI: 1.58, 1.95) and noBF (OR: 1.32; 95% CI: 1.14, 1.53), which was stronger in the younger infants. Structural equation modeling shows that a) IF3d was associated with higher IFcur (std β: 0.244), which in turn linked with noBF (std β: 0.285) and b) IF3d was associated with cesarean delivery (std β: 0.627), intention of feeding formula at birth (std β: 0.556), and lack of professional breastfeeding support at birth (std β: 0.213; P < 0.01 for all). Support for exclusive breastfeeding in the first 3 days of life can reduce early introduction of infant formula and early cessation of breastfeeding.

Funding: Bill & Melinda Gates Foundation, through Alive & Thrive, managed by FHI 360
Vitamin B12 Status in a Cohort of Canadian Pregnant Women and Newborn Infants
Authors: Visentin Carly , Masih Shannon , Plumptre Lesley , Schroder Theresa , Sohn Kyoung‐Jin , Ly Anna , Nielsen Daiva , Lausman Andrea , Berger Howard , Croxford Ruth , Lamers Yvonne , O'Connor Deborah , Kim Young‐In
Published: June 2021

Low maternal concentrations of vitamin B12 (B12) adversely affect fetal development. In Canada, low serum B12 concentrations (<148 pmol/L) are prevalent among women of reproductive age. We measured concentrations of serum B12 and its functional biomarkers, plasma total homocysteine (tHcy) and methylmalonic acid (MMA), in 368 pregnant women at 12‐16 wk gestation, at delivery and in cord blood. We also determined the effect of major fetal genetic variants of B12 metabolism on cord plasma concentrations of B12, tHcy and MMA. The prevalence of low serum B12 concentrations at recruitment and delivery was 17% and 37%, respectively. Elevated plasma MMA concentrations (>270 nmol/L) were only observed in 2% and 5% of women at recruitment and delivery, respectively, and no women had plasma tHcy concentrations >13 μmol/L. During pregnancy, mean serum B12 concentrations decreased by 23%, while plasma tHcy and MMA increased by 20% and 24%, respectively (p<0.0001). Mean cord blood concentrations of B12, tHcy and MMA were 1.9, 0.8 and 2.3 times maternal concentrations at delivery (p<0.0001). Cord plasma MMA concentrations were significantly altered by the MTR rs1805087, MUT rs1141321 and MMAA rs2270655 genotypes (p<0.04), while cord serum B12 and plasma tHcy concentrations were altered by the TCN1 rs34324219 genotype (p=0.04). Our data suggest that although “suboptimal” serum B12 levels are prevalent in Canadian pregnant women, they are unlikely functionally significant as evidenced by MMA and tHcy status. Fetal genetic variants appear to influence cord blood concentrations of B12, MMA and tHcy. Funded by CIHR MOP#106446
Are Fathers' Feeding Practices Associated with Preschool Age Children's Diet Quality, Eating Behavior, or Weight?
Authors: Vollmer Rachel , Adamsons Kari , Foster Jaime , Mobley Amy
Published: June 2021

The aims of this study were to identify the relationship of paternal feeding practices and preschool children's 1) eating behavior, 2) diet quality, and 3) weight status. Fathers of preschoolers (n=150) were recruited to participate in a one‐on‐one interview to assess feeding practices (Child Feeding Questionnaire), child eating behaviors (Children's Eating Behavior Questionnaire), and diet quality (24 hour recall, Healthy Eating Index). Height and weight for each father and child were measured and Body Mass Index (BMI) or BMI z‐score calculated. Linear regression was used to test the study aims. Paternal feeding practices were not related to child diet quality or weight status. However, child eating behaviors were associated with child BMI z‐score and these relationships were moderated by paternal feeding practices. For example, child satiety responsiveness was inversely (β= ‐.421, p= 0.031) associated with child BMI z‐score, only if paternal restriction scores were high, and was not significant when paternal restriction scores were low (β= ‐.200, p= 0.448). These results suggest that some child appetitive traits may be related to child weight status when exposed to certain paternal feeding practices. Future studies should consider the inclusion of fathers, in addition to mothers, as their feeding practices may influence the relationship between child eating behavior and child weight.
Changes in Z‐BMI and Dietary Intake in Children Participating in a Community‐based Weight Management Program
Authors: Greene Geoffrey , Marchand Stephanie , Nobles Jennifer , Xu Furong
Published: June 2021

Reducing the rate of weight gain is critical for overweight young children to avoid obesity in adolescence which is highly predictive of adult obesity. South County Food Fitness and Fun is a community‐based, 16‐week program for 6‐10 year old children referred by their physicians with BMI > 85%. The purpose of this study was to evaluate preliminary results among children completing the intervention. Completers (n=71; mean age=8.6±1.2 years, BMI=24.5±4.0 kg/m2, 61% female) decreased Z‐BMI from 2.0±0.6 baseline to 1.9±0.6 post program (p<.001). Among those with 2‐year follow‐up (n=33), Z‐BMI decreased from 1.9±0.4 baseline to 1.7±0.6 2‐year follow‐up (p=.03). Dietary variables were assessed pre and post intervention by the Harvard Youth/Adolescent Food Frequency Questionnaire; participants with complete dietary data (n=69) decreased energy intake from 2116±504 kcal to 1886±424 kcal (p<.001) as well as decreased saturated fat from 10.3±1.6 % kcal to 9.9±1.7 % kcal (p<.05) and sodium from 2634±677 mg to 2339±523 mg (p<.001). Dietary fiber increased from 8.6±2.0 grams/1,000 kcal to 9.6±2.3 grams/1,000 kcal (p<.001). There were no changes in calcium, Vitamin D, added sugar, or potassium. In conclusion, this intervention program was associated with a reduction in the rate of weight gain in overweight children as well as an improvement in dietary quality, thus could help reduce the risk of these children becoming obese adults.
WAVE Pilot Study: Feasibility of Using Emails and Short Message Service (SMS) with High School Soccer Players to Reinforce Compliance in an Obesity Prevention Intervention
Authors: Wong Siew Sun , Meng Yu , Moissinac Béatrice , Scaffidi Christopher , Manore Melinda
Published: June 2021

Objective

Evaluate the feasibility of using emails/SMS with high school (HS) soccer players for increasing compliance at group classes, completion of questionnaires, and 7‐day tracking of eating behavior and physical activity.

Method

Customized emails/SMS using Google Voice and WavePipe (a custom data collection system that sends emails) were sent to remind and encourage compliance in 52 youth (14‐19y) enrolled in the WAVE Pilot Study. Prior to each activity, coaches and youth received emails/SMS about enrollment session, class schedule (intervention group [IG] only), and baseline assessments. During a subsequent 7‐day tracking period, youth received a daily email/SMS with a unique link to the behavioral checklist (BC) online and a reminder to wear the Fitbit.

Results

Overall, the IG was more compliant in all aspects of data collection and attending group sessions. The enrollment and survey completion rate was 76% in the IG (n=25) vs. 51% in the control group (CG) (n=27) (p<0.05). On average, the IG wore Fitbits for 6.0 d vs. 4.9 d for the CG (p<0.05); 98% Fitbits were returned. The IG completed the online BC for 3.7 d vs. 1.4 d by the CG (p<0.05). Failure to receive daily emails significantly reduced the BC response rate; 44% of the CG reported not noticing 蠅1 daily email/SMS. Other reasons include wrong contacts. Youth generally preferred SMS over emails as reminders.

Conclusion

Emails, particularly SMS, during intervention increased active HS soccer players' compliance.

Sponsor: NIFA AFRI Award No. 2013‐67001‐20418
Physical Activity is Associated with Lower Adiposity Independent of Diet Quality in Adolescent Girls
Authors: Vassallo Danielle , Thomson Cynthia , Funk Janet , Jacobs Elizabeth , Blew Robert , Lee Vinson , Going Scott
Published: June 2021

BACKGROUND

Total and site‐specific adiposity, such as visceral and skeletal muscle fat, have been associated with increased cardiovascular disease risk in adults, but data are lacking for youth. Calorically dense diets are major contributors to the development of childhood obesity and metabolic diseases.

OBJECTIVE

To assess the relationships between diet quality (DQ), measured by the Youth Healthy Eating Index (YHEI), physical activity (PA), and measures of total and site‐specific adiposity in 211 healthy girls aged 8‐13 years.

METHODS

Muscle density (MD, mg/cm3), surrogate for fat infiltration, was measured at tibia and femur sites using peripheral quantitative computed tomography. Total body and android fat (surrogate for visceral fat) were measured by dual energy x‐ray absorptiometry. Diet was assessed using the validated semi‐quantitative Harvard Youth/Adolescent Food Frequency Questionnaire (YAQ). DQ was assessed from the YHEI, developed based on the YAQ. PA was assessed using a past year PA questionnaire.

RESULTS

Multiple linear regressions with DQ, maturity, total energy intake, and PA were used to predict MD, total body fat (BF), android fat (AF), and body mass index (BMI) in separate models. DQ was not a significant predictor of adiposity. PA was positively associated with calf MD (p 蠄 0.01, β=0.62) and thigh MD (p 蠄 0.01, β=0.77) and negatively associated with BMI (p蠄0.05, β=‐0.02), AF (p蠄0.01, β=‐4.82), and BF (p蠄0.01, β=‐3.74).

CONCLUSION

PA is associated with lower adiposity independent of DQ, total energy intake, ethnicity, and maturation.

Grant Funding Source: NIH: HD050775
PAR2 Activation Protects Against Colitis but Inhibits Epithelial Wound Healing
Authors: Trusevych Elizabeth , Iablokov Vadim , Dicay Michael , Beck Paul , MacNaughton Wallace
Published: June 2021

Aims

Protease‐activated receptor (PAR)2 activation increases the expression of cyclooxygenase (COX)‐2 in intestinal epithelial cells. We tested the hypothesis that PAR2‐induced COX‐2 regulates intestinal inflammation and modulates epithelial wound healing.

Methods

PAR2 was activated using the selective activating peptide 2f‐LIGRLO. Circular wounds in Caco2 cell monolayers were monitored with live‐cell imaging. In vivo, epithelial damage was induced by giving WT and PAR2 KO (C57Bl/6) mice 2.5% DSS for 5‐7 days.

Results

Activation of PAR2 in Caco2 cells significantly increased COX‐2 protein (4.2‐fold) and PGE2 metabolites (9.6‐fold). In vivo, preliminary results showed less COX‐2 protein in PAR2 KO mice given DSS compared to WT mice. The PAR2 KO mice also lost significantly more weight and had higher histological damage scores compared to WT mice. We next determined the effect of PAR2‐induced COX‐2 on epithelial wound healing in vitro. Surprisingly, PAR2 activation significantly inhibited the rate of wound closure over 48 hr (79.3±2.5% wound closure) compared to control (94.3±0.5%), independently of COX‐2 activity. PAR2 activation had no effect on proliferation, but significantly inhibited cell migration.

Conclusions

PAR2 activation was shown to be protective in vivo, which correlated with the expression of COX‐2. We also uncovered a novel COX‐2‐independent effect of PAR2, reducing the rate of wound healing by inhibiting cell migration. Our results show that PAR2 plays differential roles in regulating epithelial response to injury and inflammation.

Support: Crohn's and Colitis Canada, Alberta IBD Consortium, Alberta Cancer Foundation.
Cross‐reactivity of Gut Commensals and Autoantigen in Antiphospholipid Syndrome
Authors: Dehner Carina , Ruff William , Vieira Silvio , Goodman Andrew , Kriegel Martin
Published: June 2021

Antiphospholipid syndrome (APS) is an autoimmune clotting disorder of unknown etiology targeting mainly the autoantigen ß2‐glycoprotein I (β2GPI). Given the vast antigenic potential of the gut microbiota and its general influence on autoimmune disease models, we hypothesized that a homeostatic adaptive immune response to gut commensals can trigger and sustain autoreactive T and B cells via cross‐reactivity with b2GPI. Protein BLAST and Clustal Omega queries identified the common human gut commensal Roseburia intestinalis as containing peptide sequences with high homology to the immunodominant ß2GPI T and B cell epitopes. We present here initial studies examining T and B cell reactivity to gut commensals in human APS patients. Patient PBMCs proliferated significantly more to R. intestinalis protein extracts compared to phylogenetically related Eubacterium rectale, which lacks homologous sequences. We successfully cloned ß2GPI‐specific memory T cells using a T cell library assay to determine next if these clones cross‐react with candidate commensals. Western blot experiments using patient plasma samples showed reactivity with several commensals, notably also with R. intestinalis including one protein at 24 kDa that may be cross‐reactive based on in silico experiments. We next adsorbed plasma from APS and control subjects with recombinant ß2GPI prior to Western blotting observing a decrease in the R. intestinalis 24 kDa band. These data support a working model where lymphocytes specific to commensals cross‐react with human autoantigen and vice versa. This process could sustain APS pathogenesis in vivo.
TNF Modulates The Gut Microbiota And Drives Inflammation
Authors: Kozik Ariangela , Jones‐Hall Yava , Nakatsu Cindy
Published: June 2021

Inflammatory Bowel Disease (IBD) consists of Ulcerative Colitis and Crohn's Disease (CD). The etiology remains unclear; however tumor necrosis factor (TNF) is known to promote the inflammation seen in these diseases. Many patients with IBD have elevated systemic and local levels of TNF and are treated with anti‐TNF drugs with variable success. It is also clear that the gut microbiota play a role in the development and perpetuation of IBD. We hypothesize that TNF modulates the gut microflora and that the severity of colitis correlates with specific microbiota shifts. To address our hypothesis, we examined the gut microbiota in mouse models of acute and chronic Trinitrobenzenesulfonic acid (TNBS) induced colitis in the presence (Wildtype, WT) and absence of TNF (TNF KO). Mice were given 1intra‐rectal (IR) injection (acute) TNBS. Feces were collected for DNA extraction and microbiome analyses. TNBS treated WT mice had more inflammation than TNBS treated TNF KOmice, proving that TNF drives inflammation in the acute model. Analyses of the fecal microbial communities at both days 0 and 10 revealed significant,Tnf‐dependent, differences in alpha and beta diversity, as well as notable differences in many species that were also primarily Tnf‐dependent. The results of the microbial analyses coupled with the results of the pathology support our hypothesis that TNF modulates the gut microbiota, which contributes to the severity of acute colitis. Analyses of the chronic studies are ongoing. We expect to see similar inflammatory results WT and TNF KOmice, with the potential for additional shifts in the microbiota as disease progresses from acute to chronic.
Mutations of Nrf2 are an early and frequent event in the development of rat hepatocellular carcinoma
Authors: Columbano Amedeo , Giordano Silvia , Perra Andrea , Kowalik Marta , Ledda‐Columbano Giovanna , Petrelli Annalisa , Menegon Silvia , Quagliata Luca , Terracciano Luigi , Zavattari Patrizia
Published: June 2021

Hepatocellular carcinoma (HCC) is a multistage process, but the nature of the molecular changes associated to the different steps, particularly the very early ones, is unknown. The Nrf2–Keap1 pathway is now recognized as a major cellular defense mechanism against oxidative and electrophilic stresses; however, its exact role in cancer development is unclear.

To unveil the role of Nrf2 in HCC, we used the Resistant‐Hepatocyte (R‐H) rat model, which identifies distinct lesions (preneoplastic foci, dysplastic nodules, early and advanced HCCs) at well‐defined timings.

The results showed that mutations of Nrf2 are very frequent in early preneoplastic lesions positive for the putative progenitor cell marker cytokeratin‐19 (KRT‐19), which are considered to be the precursor cell population of HCC in this model. All the mutations were missense, involved the Nrf2‐Keap1‐ binding regions and were associated with a strong increase of expression of the Nrf2‐target genes (Nqo1, Gclc,Gst4), in both pre‐ and neoplastic lesions. KRT‐19 positive HCCs arising 10 and 14 months later also showed a high percentage of Nrf2 mutations (70 and 56%, respectively), suggesting that mutation of this gene is critical for HCC development. Nrf2 silencing inhibited the ability of rat tumorigenic cells to grow in soft agar and to develop HCC when injected into syngeneic rats.

Conclusion

This study demonstrates that Nrf2 mutation is a very early and frequent event, suggesting that dysregulation of the Nrf2‐Keap1 pathway is likely essential for the clonal expansion of KRT‐19+ preneoplastic hepatocytes to HCC.
PPARα: A Novel Target in Pancreatic Cancer
Authors: Hua Alexander , Casper Jessica , Bielenberg Diane , Schmidt Birgitta , Kieran Mark , Panigrahy Dipak , Gus‐Brautbar Yael
Published: June 2021

Background

The tumor stroma is increasingly implicated in pancreatic cancer. Pancreatic cancer is characterized by a highly fibrotic tumor microenvironment resulting in stromal resistance to chemotherapy. Peroxisome proliferator activated receptor alpha (PPARα), a ligand‐activated nuclear receptor/transcription factor, is a key negative regulator of inflammation. In PPARα deficient mice, stromal processes inhibited tumor growth resulting in dormant tumors. We hypothesized that blocking the PPARα pathway with a small molecule PPARα antagonist (NXT00120) may inhibit pancreatic cancer by targeting inflammation and cell signaling pathways that regulate cell cycle progression.

Results

Systemic administration of the PPARα antagonist, NXT00120, inhibited primary human pancreatic cancer cancer (HPAF‐II) and ascites formation in an aggressive orthotopic pancreatic cancer model. Combination of NXT00120 with gemcitabine induced sustained tumor regression in an orthotopic model of pancreatic cancer (PancOH7). NXT00120 reduced levels of phospho‐AKT, AKT, PCNA, Cyclin‐D1, RB protein levels.

Conclusion

We demonstrated NXT00120 induced proliferation arrest by negatively modulating cell cycle regulatory proteins. Targeting pancreatic cancer with a PPARα antagonist is an entirely novel approach to complement chemotherapy to combat pancreatic cancer.

Research Support: ROCA148633
High MUC2 Production in Goblet Cells Induces ER Stress and Exhibit Increase Susceptibility to Apoptosis
Authors: Tawiah Adelaide , Moreau France , Chadee Kris
Published: June 2021

MUC2 is a large glycoprotein produced by goblet cells (GC) that form the protective mucus blanket overlying the intestinal epithelium. During pathological conditions such as IBD or colonic cancers, MUC2 biosynthesis and secretion are accelerated. Little information is known on how MUC2 production is regulated and whether GC undergoes endoplasmic reticulum (ER) stress following high MUC2 biosynthesis. We studied the role of MUC2 in GC stress using a high MUC2 producing GC line, HT29‐H, and a clone of HT29‐H (HT29‐L) in which MUC2 was stably silenced using lentivirus shRNA. Cells were treated with the ER stressor, tunicamycin (TUN) and markers for ER stress (GRP78, ATF4, CHOP, sXBP1) and apoptosis (caspase 3 and PARP cleavage) quantified by western blotting and RT‐qPCR. Compared to HT29‐L, HT29‐H cells showed significant increase in ER stress and apoptosis in response to TUN. Over expressing MUC2 in non‐MUC2‐producing SKCO15 cells also increased ER stress and apoptosis confirming specificity of MUC2. Pre‐treatment of cells with reactive oxygen species (ROS) inhibitor, diphenyleneiodonium, abrogated basal stress levels, TUN‐induced ER stress and apoptosis. HT29‐H constitutively produced significantly more ROS than HT29‐L cells indicating that high MUC2 production specifically increases ROS production that drives ER stress and apoptosis. These findings were corroborated in isolated colonic epithelial cells and colonic tissues from Wt and Muc2‐/‐ mice that showed significant increase in ER stress in Wt as compared to Muc2‐/‐ mice. We conclude that high MUC2 production by GC induces ER stress and apoptosis that could subsequently lead to diminished mucus barrier function in disease pathogenesis.

Grant: CIHR
AT101 Down‐regulates CXLC12 mRNA and Secreted Protein in Malignant Peripheral Nerve Sheath Tumor cells
Authors: Graham Christopher , Kaza Niroop , Klocke Barbara , Roth Kevin
Published: June 2021

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive, Schwann cell‐derived neoplasms of the peripheral nervous system. MPNSTs have recently been shown to possess an autocrine CXCL12/CXCR4 signaling loop that promotes tumor cell proliferation and survival. Importantly, the CXCL12/CXCR4 axis is driven by availability of the CXCL12 ligand rather than CXCR4 receptor levels. Accordingly, pharmacological reduction of CXCL12 expression and/or secretion could be a potential chemotherapeutic option for patients with MPNSTs or other malignancies wherein the CXCL12/CXCR4 axis is relevant. AT101 is a polyphenolic cottonseed derivative with well‐established Bcl‐2 homology domain 3 (BH3)‐ mimetic properties. We recently reported that AT101 can also chelate intracellular iron and therefore act as a hypoxia mimetic. Importantly, we have observed that AT101 causes a marked reduction in CXCL12 mRNA and secreted protein levels in cultured MPNST cells. This property of AT101 was recapitulated by other BH3‐mimetics (ABT‐737, obatoclax and subatoclax) but not by desferrioxamine (DFO), an iron chelator and known hypoxia‐mimetic. These data indicate that CXCL12 reduction is likely a function of AT101′s BH3‐mimetic property rather than its iron chelation ability. Ongoing studies are aimed at addressing the mechanism by which AT101 and other BH3‐mimetics reduce CXCL12 mRNA and protein in MPNST cells.
The Effect of Image Quality and Image Presentation on the Recall of Anatomic Knowledge.
Authors: Wainman Bruce , Norman Geoffrey , Fenesi Barbara , Mackinnon Chelsea , Cheng Lucia , Kim Joseph
Published: June 2021

Of the seemingly infinite number of learning objects available for anatomy education, which are the best? This simple question has led to two main research thrusts in our lab. The first question examines the relative efficacy of virtual reality models, static images demonstrating key views, and models in learning anatomy. The second looks at whether image quality matters to anatomy education. We have found that simple anatomic models are better than static images, while both simple models and static images are far better than virtual reality models for recall of anatomic knowledge. Further, we have found that the quality of 2D anatomic illustrations does not alter anatomic recall. This presentation will describe the data and cognitive science supporting our results.
A biomedical synthesis of the zygoma: bone elastic properties, morphology and function, and reconstructive medicine
Authors: Dechow Paul , Wang Qian , Pryor Smith Leslie
Published: June 2021

The zygomas form the prominent anterolateral structure of the midfacial skeleton. Functionally different from most cranial bones, the zygoma is subject to large strains because of the forces of the masseter muscle attached to the zygomatic arch, in addition to the indirect support of molar bite forces due to articulation between the zygomatic body and the maxilla. Clinically, there is a high tendency of the zygoma to fracture during trauma, which affects the integrity of the facial skeleton, demanding careful reconstruction. Thus, bone characters in the zygoma are of special importance in functional analysis and reconstructive medicine. Using ultrasonic techniques, microCT, cone beam radiography, and histological techniques, our laboratory has studied the material properties, and microstructure of the zygoma in a variety of primates including humans. Results have shown that across taxa the arch is the most anisotropic region of the cranial skeleton. Surprisingly, there is much inconsistency in the trabecular structure of the zygoma, with some taxa having little trabeculae and a nearly solid bony structure. This is not the case in humans where the bone is highly trabeculated and thus relatively weaker than in some primate species, suggesting that the human zygoma is more prone to injuries; a multidisciplinary approach considering both external and internal bone structures would promote functional recovery.

Supported by the NSF Physical Anthropology HOMINID program NSF BCS 0725141.
Biomechanical studies of the zygoma: A review of in vivo (italic) and FEM studies of the lateral orbital wall and zygomatic arch
Authors: Ross Callum , Strait David , Ledogar Justin , Smith Amanda , Villmoare Brian , Benazzi Stefano , Weber Gerhard , Spencer Mark , Dechow Paul , Grosse Ian , Richmond Brian , Wright Barth , Wang Qian , Byron Craig , Slice Dennis , Carlson Kristian , de Ruiter Darryl , Berger Lee , Tamvada Kelly , Pryor Smith Leslie , Gundel Annemarie
Published: June 2021

The zygomatic region and lateral orbital wall are important structural components of the primate craniofacial skeleton, providing attachment for muscles, housing and protecting the eye, and resisting and transmitting forces incurred during feeding and fighting. The design of this region must therefore meet the needs of a number of different functional systems. The relative importance of these different systems in driving zygomatic morphology across different primate lineages remains to be elucidated. The role of this region in resisting, transmitting and dissipating feeding forces is amenable to study using in vivo bone strain and finite element modeling techniques. Based on these techniques Ross et al. (2011) suggested that there is a common pattern of deformation of the catarrhine facial skeleton, namely bending in frontal/coronal planes. Following Endo (1966) and Rak (1983), this bending was hypothesized to be due to inferiorly directed muscle forces acting on the zygomatic arches, producing torsion and sagittal bending of the arches. The highest strains and stresses associated with this deformation regime are experienced by the anterior root of the zygoma. The bone in this area is hypothesized to experience high shear stresses resulting from inferiorly directed muscle forces laterally and superiorly directed bite forces medially. This model was based on in vivo bone strain data from Macaca, Papio, and Chlorocebus, frame‐modeling of Gorilla and Homo, and finite element modeling (FEM) data from Macaca. Review of the available bone strain and/or FEM data for Cebus,Pan, and several fossil hominins reveals common patterns of strain across taxa with a range of morphologies and diets. Bone strain magnitudes in the arch and anterior root are high relative to strain magnitudes elsewhere in the cranium, suggesting an important role for structural strength in the design of this region. The notion of a fundamental framework of the catarrhine face receives some support from these data.
Regulation of the Blood‐Brain Barrier in Health and Disease
Authors: Daneman Richard
Published: June 2021

Vascular endothelial cells in the central nervous system (CNS) form a barrier that restricts the movement of molecules and ions between the blood and the brain. This blood‐brain barrier (BBB) is crucial to ensure proper neuronal function and protect the CNS from injury and disease. Although the properties of the BBB are manifested in the endothelial cells, transplantation studies have demonstrated that the BBB is not intrinsic to the endothelial cells, but is induced by interactions with the neural cells. Here we use a genomic, genetic and molecular approach to elucidate the cellular and molecular mechanisms that regulate the formation of the BBB. We have identified a critical role for pericytes in regulating the permeability of CNS vessels by inhibiting the properties that make endothelial cells leaky. In particular pericytes limit the rate of transcytosis through endothelial cells as well as the expression of leukocyte adhesion molecules in CNS endothelial cells, which limits CNS immune infiltration. Furthermore, we have developed methods to highly purify and gene profile endothelial cells from different tissues, and by comparing the transcriptional profile of brain endothelial cells with those purified from the liver and lung, we have generated a comprehensive resource of transcripts that are specific to the BBB forming endothelial cells of the brain. We have further examined the profile of CNS endothelial cells following injury and disease and have identified molecular mechanisms by which pericytes control BBB formation, which are then disrupted during neurological disease leading to BBB dysfunction.
Quantifying the Connectivity of the Language‐Specific Cerebrocebellar Network (LSCN)
Authors: George Ian , Beversdorf David , Aldridge Kristina
Published: June 2021

Language was arguably a key influence in the evolution of the human brain and the evolution of this behavior in humans was likely associated with gross morphological changes and novel neural networks. Our previous research examined one such network and verified anatomical connectivity between regions of the cerebellum, thalamus, and frontal lobe active during language using a combination of magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). The results of the DTI analysis and fiber tracking support the hypothesis that there is discrete anatomical connectivity in a language‐specific network.

Our current study is designed to characterize and quantify this anatomical connectivity in the language‐specific functional network between the cerebrum and cerebellum. We analyzed the language‐specific cerebrocerebellar network (LSCN) in 30 right‐handed neurotypical males through DTI images. Our results show the white matter tracts in the LSCN have greater connectivity than that of the white matter in the whole brain, indicating that there is a discrete network between the cerebrum and cerebellum exclusively for language. Information about the anatomical connectivity in this neural network can now be used in conjunction with behavioral measures to shed light on the evolution of the human brain, evolution of language, and pathologies that affect language production.

This research was funded by the Wenner‐Gren Foundation, the MU Life Sciences Fellowship, Pearson, and the MU Brain Imaging Center.
Understanding the Mechanisms Driving Ectopic Bone Formation in a Zebrafish FOP Model
Authors: LaBonty Melissa , Yelick Pamela
Published: June 2021

Introduction: The zebrafish Type I TGFβ family member receptor, Alk8, modulates BMP/TGFβ signaling to promote cartilage and bone formation. Activating mutations in the human ortholog of Alk8, ACVR1 (ALK‐2), are associated with the disease Fibrodysplasia Ossificans Progressiva (FOP), characterized by the gradual ossification of fibrous tissues. The objective of this study is to develop a zebrafish model to identify and characterize molecular mechanisms underlying FOP.

Methods: Gateway cloning, transgenesis, Alcian blue stain, Alizarin Red Stain, μCT, IHC

Results: Gateway cloning was used to generate Tol2 vectors containing a heat shock promoter driving the expression of mCherry tagged wild type (WT), dominant negative (DN), or constitutively active (CA) Alk8. The Tol2 vectors were co‐injected with Tol2 transposase mRNA into single cell staged BMP response element reporter (BRE:GFP) zebrafish to produce transgenic animals. Transgenic lines were subjected to short term (1‐3 weeks) or long term (1‐3 months) daily heat shock intervals to induce variant Alk8 expression. μCT, Alcian blue, and Alizarin red staining were used to characterize changes in mineralization patterns. CA‐Alk8‐expressing zebrafish exhibited enhanced mineralization and ectopic bone formation as compared to WT and non‐heat shock controls. In contrast, DN‐Alk8‐expressing animals exhibited reduced mineralization. IHC analyses of phosphorylated SMADs and other BMP and TGFβ downstream targets are being used to identify the molecular and cellular mechanisms driving aberrant mineralization.

Conclusions

Heat shock inducible Alk8 variants in Zebrafish provide informative models for ectopic bone formation in human FOP.

Support: NSF GRFP NS9344 (ML), NIH/NIDCR R01 DE016962 (PCY), R01 DE018043 (PCY), and R21 HD085013 (PCY).
TRPV Channel Structures in Health and Disease
Authors: Gaudet Rachelle
Published: June 2021

My lab is broadly interested in the mechanisms of signaling and transport across cellular membranes. Much of our research centers on TRP channels and their role in sensory perception. We focus on temperature‐sensitive ion channels, particularly TRPV1, TRPV4 and TRPA1. TRP channels are challenging structural biology targets because they are large multidomain eukaryotic membrane proteins and are not naturally abundant. We take complementary approaches to obtain structural and functional information on TRP channels, including crystallography, biochemistry and cell‐based functional assays. The combined results advance our understanding of TRP channel function. TRPV channels play key roles in pain, thermo‐ and mechanosensation, and calcium homeostasis, and mutations in the TRPV4 channel have been implicated in both neuronal degeneration diseases and skeletal dysplasias. The N‐terminus of TRPV channels contains six ankyrin repeats, short sequence motifs often involved in protein‐ligand interactions. The isolated ARDs do not oligomerize, suggesting that they interact with regulatory factors instead. Our accumulated data provide information about how regulatory ligands interact with the ARD and other N‐ and C‐terminal intracellular regions and alter the sensitivity of these TRPV channels.
The Holistic Review Approach to Admissions
Authors: de la Rosa Jose
Published: June 2021

This presentation will review the reasons medical schools have begun to change their admissions processes in order to develop compliance with their admissions policies. It is recognized that schools of medicine wished for methodologies to access non‐cognitive abilities desired in future physicians. The process of “holistic review” provides a methodology to review applicants.

Beginning with the decision to invite an applicant for interview, an assessment must be made of both cognitive and non‐cognitive abilities of the candidate. Traditionally the interview has been the non‐cognitive instrument for assessment of non‐cognitive abilities. This presentation will review the development of rubrics and other techniques to assess other non‐cognitive abilities, including the new medical college admissions test, the M.M.I. and secondary applications. A question and answer period will be entertained to assist in the understanding of the objectives.
Ultra‐processed and Ready‐to‐eat Food and Beverage Purchases Differ by Race, Education, and Income in a Longitudinal US Study
Authors: Poti Jennifer , Mendez Michelle , Ng Shu Wen , Popkin Barry
Published: June 2021

It is not clear whether processed foods contribute to sociodemographic disparities in the diets of Americans. Our objective was to determine whether race/ethnicity, education, and income were associated with ultra‐processed or ready‐to‐eat food and beverage purchases among US households. We analyzed data from the 2000‐2012 Homescan panel (n=157,142). We classified 1.2 million barcoded products by level of food processing and convenience. Longitudinal random effects linear and multinomial logistic regression models were used to examine time‐varying associations.

The calorie contribution of ultra‐processed products to food purchases was 蠅58% for all subpopulations. Inverse associations of ultra‐processed food purchases with education and income emerged across time as households of higher, but not lower, socioeconomic status (SES) shifted away from these foods. Compared to white households, black households had higher ultra‐processed beverage purchases yet lower ultra‐processed food purchases. Blacks were more likely than whites to be in the highest quartile for purchases of moderately processed foods (predicted probability: 45.8% vs 21.0%) and foods requiring cooking (41.3% vs 21.7%) and purchased more cooking oils and table sugar. Black race and lower education were associated with lower ready‐to‐eat convenience food purchases. Findings suggest that ultra‐processed foods among low SES households and ultra‐processed beverages among blacks may contribute to US diet disparities. Sociodemographic differences in patterns reflective of greater home‐cooking warrant further study.

Funding source: Robert Wood Johnson Foundation (67506, 68793, 70017, 71837), NIH (R01DK098072), CPC 5 R24 HD050924
Country and Region of Origin Predict Risk of Food Insecurity among Hispanic‐born in US
Authors: McClain Amanda , Dickin Katherine , Dollahite Jamie , Gurak Douglas
Published: June 2021

Reports on food insecurity often lump Hispanics together, ignoring potential geographical and cultural differences that may be important for identifying and targeting at‐risk populations. The objective of this analysis was to determine the influence of Hispanic country and region of origin on US household and child food security status.

We analyzed data from the December 2013 supplement of the Current Population Survey. We tested logistic regression models of household and child food insecurity among persons born in a Hispanic country versus the US, the reference group. Models controlled for significant predictors of food insecurity: income, number of children < 18y, education, marital status, and Hispanic ethnicity. We adjusted estimates with survey weights for persons.

Persons originating from Mexico (p=0.00; OR=1.22) and Puerto Rico (p=0.02; OR=1.39) were at significantly higher risk of household food insecurity than US‐born. Mexico‐born persons (p=0.00; OR=1.28) were at significantly higher risk of child food insecurity than US‐born. Central American, South American, and Dominican‐born persons did not differ from US‐born. SNAP and WIC participation were associated with increased risk and attenuated differences between US‐born and Mexican‐born, and US‐born and Puerto Rican‐born persons.

Findings suggest that country and region of origin for Hispanics, particularly Mexican‐born, may influence food insecurity risk and be an important factor for targeting interventions to reduce food insecurity among Hispanics. Promoting WIC and SNAP participation may be one effective approach.

[Funding: Research Innovation and Development Grants in Economics (RIDGE) Doctoral Dissertation Research Grant]
Effects of an Eicosapentaenoic Acid and Antioxidant‐Containing Medical Food in Hypertriglyceridemia Management
Authors: Maki Kevin , Geohas Jeffrey , Dicklin Mary , Huebner Marjorie , Udani Jay
Published: June 2021

This randomized, double‐blind, placebo‐controlled multi‐center trial investigated the lipid‐altering effects of a medical food (PDL‐0101) providing 1.8 g/d eicosapentaenoic acid; 12 mg/d astaxanthin, a marine algae‐derived carotenoid; and 100 mg/d gamma/delta tocotrienol enriched with geranylgeraniol, extracted from annatto, on triglycerides (TG), other lipoprotein lipids, and oxidized low‐density lipoprotein (LDL) in subjects with hypertriglyceridemia. Participants included 102 predominantly Caucasian (72%) men (57%) and women with mean age 51.8 y, mean body mass index 31.2 kg/m2, TG 150‐499 mg/dL and LDL cholesterol (LDL‐C) 蠅70 mg/dL. Compared to placebo, after 8 wks of treatment, PDL‐0101 significantly lowered median TG (‐9.5% vs. 10.6% for PDL‐0101 and placebo, respectively, p < 0.001), while not significantly altering mean LDL‐C (‐3.0% vs. ‐8.0% PDL‐0101 and placebo, respectively, p = 0.071), mean high‐density lipoprotein cholesterol (HDL‐C; ~3% decrease in both, p = 0.732), or median oxidized LDL (5% vs. ‐5% PDL‐0101 and placebo, respectively, p = 0.112). PDL‐0101 was also more effective for lowering TG in the subset with TG 蠅200 mg/dL (‐12.7% vs. 9.8% PDL‐0101 and placebo, respectively, p < 0.001). There were no significant differences in responses to treatment in total‐C, non‐HDL‐C, or apolipoprotein B. These results demonstrate that PDL‐0101 is a well‐tolerated and effective medical food for managing elevated TG. Funded by Primus Pharmaceuticals, Inc. (Scottsdale, AZ) and Designs for Health, Inc. (Suffield, CT).
Effect of iron supplementation with or without vitamin E (VE) on gut microbiome (MB) in iron deficient (ID) infants and toddlers
Authors: Tang Minghua , Frank Daniel , Ir Diana , Krebs Nancy
Published: June 2021

Objective

To assess the impact of VE on the efficacy of therapeutic iron and on gut MB in infants and toddlers with ID.

Design

This is a randomized, double blind efficacy trial of 8 weeks of iron therapy (6 mg/kg/d) alone or with VE, in 9‐24 mo old infants and toddlers with ID. Profiles of fecal gut MB were measured by 16S sequencing before and after treatment.

Results

32 infants (14 ± 4 mo) completed the study with pre‐ and post‐trial stool samples collected (IG: Iron Group n=18; IVEG: iron +VE Group n=14). Over time, allparticipants improved iron status. Compared with IG without group difference. Compared with IG, the IVEG had increase in serum vitamin E concentration (Δ1.3 ± 6.1 mcg/ml, P < 0.05). Microbial diversity increased overtime (P < 0.01) among all participants. Firmicutes increased (P < 0.05) and Bacteroidetes decreased (P < 0.05) in relative abundance (RA) in the IVEG, compared with IG. A group‐by‐time interaction was observed in which Bacteroidaceae (P = 0.07) and Bacteroides (P = 0.07) decreased, while the potential butyrate producers Lachnospiraceae (P = 0.01 and Roseburia (P = 0.04) increased in RA in the IVEG. Among all participants, correction of ID was associated with decreased Escherichia from 1.4% to 0.4% (P =0.01). Age and breastfeeding exposure had no impact on the results.

Conclusion

Improving iron status in U.S. infants and toddlers with ID reduced the abundance of putative pathogens. Adding VE to iron supplement beneficially affected the gut microbiome.

Sponsored by: The Gerber foundation, NIH/NIDDK (K24 DK083772), Colorado CTSI, UCD Microbiome Research Consortium
Interactive Effects of Protein Deficiency and Intestinal Nematode Infection During Pregnancy on Expression of Growth Genes in Placenta of Mice
Authors: Starr Lisa , Scott Marilyn , Koski Kristine
Published: June 2021

Background

Protein deficiency (PD) and intestinal nematode infection during pregnancy impair distinct aspects of fetal growth. We used microarrays to test the hypotheses that maternal PD and nematode infection have interactive effects on placental functions related to growth and that this would be evident in altered placental gene expression

Methods

Placentae were obtained on day 18 of pregnancy from CD‐1 mice fed protein sufficient (24% protein) or protein deficient (6% protein) isoenergetic diets and either uninfected or infected every 5 days with Heligmosomoides bakeri beginning on day 5 of pregnancy. Pathway analysis was performed on differentially expressed genes identified by Affymetrix GeneChip 2.0 ST mouse arrays.

Results

In response to H. bakeri, 323 transcripts were differentially expressed, including oxidative phosphorylation, ATP binding and hemopoiesis genes. In response to PD, 272 transcripts were differentially expressed, including endopeptidase activity and hemopoiesis genes. A significant interaction was observed for 248 transcripts, including several genes with functions in fetal growth. Notably, infection prevented PD‐induced down‐regulation of IGF‐1 receptor, insulin receptor substrate and prolactin.

Conclusion

In addition to their independent effects, the interaction of maternal PD and intestinal nematode infection had antagonistic effects on placental genes involved in fetal growth. These results highlight the complexity of fetal growth regulation during combined malnutrition and infection.

Funding Natural Science and Engineering Council of Canada
Dietary Protein Quantity and Source Impact Weight and Body Composition of Older Adults: Analysis of NHANES 2001‐2006 Data
Authors: Campbell Wayne , Kim Jung Eun , Chen Ningning , Fulgoni Victor
Published: June 2021

We assessed the effect of dietary protein on weight and body composition (BC) of older adults using dietary (food records) and BC (DXA) data from NHANES 2001‐2006. Data from 5,102 men and women, aged 50+ y, were analyzed using multiple linear regressions with age, sex, ethnicity, BMI, and carbohydrate and fat intakes as co‐variables and protein intake as a categorical variable separated into quartiles. Among all subjects, the 5th, 25th, 50th, 75th, and 95th percentiles of total protein intake (TPro, g•kg‐1•d‐1, mean±SE) were 0.51±0.01, 0.73±0.01, 0.92±0.01, 1.14±0.01, and 1.51±0.03, respectively. Higher TPro predicted lower weight, fat mass (FM, kg), FM%, FM index (kg/m2) and non‐bone lean mass (LM, kg), and higher LM% and LM index (kg/m2) for all subjects (all P‐values <0.007). Total bone mineral content (BMC, kg) and bone mineral density (BMD, g/cm2) were not influenced, and BMC index (kg/m2) was higher with higher TPro. Relationships between sources of protein (dairy, non‐dairy animal, and plant) and these BC parameters were varied. In general, the protein intake‐related patterns for weight and the indices of soft tissue BC related to TPro also were shown for non‐dairy animal and plant protein, but not dairy protein. For bone, higher intakes of dairy, non‐dairy animal, and plant protein intakes were not associated with BMC or BMD, while higher dairy protein intake predicted higher BMC index. These epidemiological results underscore the importance of dietary protein for weight control and improved adiposity and bone among older adults in the United States.

Support: Dairy Res. Inst.