bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human milk oligosaccharides protect bladder epithelial cells against uropathogenic E. coli and Streptococcus agalactiae infections (38.5)
Authors: Lin Ann , Autran Chloe , Espanola Sophia , Lewis Amanda , Bode Lars , Nizet Victor 
Published: June 2021

Urinary tract infection (UTI) is primarily caused by uropathogenic E. coli (UPEC) and sometimes Streptococcus agalactiae (GBS). Recurrent infection that can progress to life‐threatening renal failure has remained as a serious global health concern in infants. Human milk oligosaccharides (HMOs) have been detected in urine of breast‐fed, but not formula‐fed neonates. We investigated the antimicrobial properties and mechanisms HMOs deploy to elicit protection in human bladder epithelial cells. We found HMO‐pretreated epithelial cells were significantly more resistant to invasion by UPEC CFT073, a prototypic strain causing urosepsis. However, HMO pre‐treatment had no significant effect in interfering with UPEC adhesion. Conversely, HMO pre‐treated cells suffer significantly less GBS COH‐1 adhesion and invasion. This result was recapitulated in vivo, in which significantly less GBS was recovered from the bladder of mice treated with HMOs. While HMOs do not play a role in maintaining host cell viability during GBS infection, we found HMOs treatment rapidly UPEC‐mediated host cell cytotoxicity. Moreover, the sialic acid‐containing fraction of HMOs reduced UPEC‐mediated MAPK and NF‐κB activation. Collectively, we showed that HMOs protect the urinary tract from microbial infection, and may be a contributing mechanism underlying the epidemiological evidence of reduced UTI incidence in breast‐fed infants.Grant Funding Source: Canadian Institutes of Health Research (CIHR)
The effect of BMI on the immunoglobulin subclass response to influenza vaccination (382.1)
Authors: Neidich Scott , Milner J , Xiao Ping‐jie , Patel Nikita , Mensah‐Biney Kevin , Hudgens Michael , Beck Melinda 
Published: June 2021

Vaccination with influenza vaccine is the best method to prevent or lessen infection with influenza virus. While obesity is an independent risk factor for developing severe influenza infection, the efficacy of influenza vaccine in obese humans is an emerging research area. We have previously demonstrated that serum titers of influenza vaccine specific IgG has a steeper decline one year post vaccination in an obese population compared with healthy weight individuals. To determine if subclasses of immunogloblulin (Ig) IgG or total IgM were also impaired in an obese population post influenza vaccination, we assessed the immunoglobulin response to influenza vaccination in adults. Patients visiting the UNC Family Practice Health Center to receive the 2012‐2013 seasonal trivalent influenza vaccine (TIV) were invited to participate in this study. A blood sample was drawn prior to receiving the vaccine, as well as thirty days post vaccination. Height and weight measurements were used to calculate BMI. Using an ELISA, pre and post vaccination serum samples were analyzed for TIV‐specific IgM, IgG1, IgG2, IgG3, IgG4, as well as total IgG. We report here that obesity was associated with a lower IgG1 response post vaccination in 18‐35 year old participants compared with healthy weight and overweight individuals. Participants above the age of 61 had decreased levels of IgM and IgG3, compared to younger participants, regardless of weight status. These data suggest that immunoglobulin subclasses are independently affected by weight status and age and may play a role in the increased susceptibility to severe influenza infection found in obese individuals.Grant Funding Source: Supported by the National Institutes of Health
n‐3 Polyunsaturated fatty acids reduce Th17 polarization by decreasing responsiveness to interleukin‐6 (382.3)
Authors: Allen M. Jeannie , Fan Yang‐Yi , Monk Jennifer , Hou Tim , Barhoumi Rola , McMurray David , Chapkin Robert 
Published: June 2021

CD4+ effector T cell subsets (e.g., Th1, Th17) are implicated in autoimmune and inflammatory disorders such as multiple sclerosis, psoriasis and rheumatoid arthritis. We have demonstrated that n‐3 polyunsaturated fatty acids (PUFA), when supplied in the diet or in fat‐1 transgenic mice which generate n‐3 PUFA de novo, suppress CD4+ T cell activation and differentiation into pathogenic Th17 cells. We hypothesized that n‐3 PUFA alter the response of CD4+ T cells to IL‐6 in a lipid raft membrane‐dependent fashion. IL‐6 induces Th17 polarization and signals through the membrane‐bound signal transducer, gp130. Upon activation, naïve splenic CD4+ T cells from fat‐1 mice exhibited significantly lower surface expression of the IL‐6 Receptor (IL‐6R). However, the release of soluble IL‐6R was unaffected by treatment. We observed a significant decrease in the association of gp130 with lipid rafts in activated fat‐1 CD4+ T cells and a 35% reduction in gp130 homodimerization, an obligate requirement for downstream signaling. The phosphorylation of STAT3, a downstream target of IL‐6‐dependent signaling, was also decreased in response to exogenous IL‐6 in fat‐1 CD4+ T cells. Our results suggest that n‐3 PUFA suppress Th17 cell differentiation, in part, by reducing membrane raft‐dependent responsiveness to IL‐6, an essential polarizing cytokine.Grant Funding Source: Supported by the NIH and USDA‐Vegetable Crop Improvement Center
Adipose transcriptomics reveals novel genes and lincRNAs modified by n‐3 PUFA supplementation and human‐evoked endotoxemia (383.1)
Authors: Ferguson Jane , Xue Chenyi , Ballantyne Rachel , Gosai Sager , Li Mingyao , Reilly Muredach 
Published: June 2021

Long‐chain omega‐3 polyunsaturated fatty acids (n‐3 PUFA) may be protective in cardiometabolic disease through modulation of chronic low‐grade systemic and adipose inflammation. However the effect of n‐3 PUFA supplementation on resting biomarkers is subtle; intervention studies often lack power to detect significant effects. The objective of the present study was to use unbiased adipose transcriptomics and evoked endotoxemia in human as a powerful model for genomic discovery in n‐3 PUFA supplementation and inflammation. We collected adipose tissue biopsies from healthy individuals before and after n‐3 PUFA supplementation (3600mg/day EPA/DHA) for 6‐8 weeks compared with placebo (N=8 per group), and following an inflammatory challenge (LPS 0.6 ng/kg).Using unbiased transcriptomics (RNASeq) we profiled adipose tissue gene expression before and after n‐3 PUFA supplementation, and after LPS challenge. We discovered a number of genes and lincRNAs that were significantly regulated by n‐3 PUFA supplementation, including down‐regulation of inflammatory genes (IL1RN, IFI30, PLA2G7), lipid‐related genes (ELOVL6, NCEH1) and novel lincRNA (linc‐ARF6‐1). Further, the transcriptomic response to LPS differed between the n‐3 PUFA and the placebo group. We found increased up‐regulation of S100A8 and S100A9 in n‐3 PUFA compared with placebo; these pro‐inflammatory and inflammasome‐activating genes protect against pathogens through formation of their heterodimer, calprotectin. Thus, a novel mechanism of n‐3 PUFA protective effects in vivo may be through increased expression of S100A8 and S100A9 in response to innate immune activation. Unbiased transcriptomics is a powerful genomic discovery tool in the context of nutritional intervention and evoked inflammatory phenotypes.Grant Funding Source: Supported by NIH R01‐HL‐113147, UL1RR024134, P20‐DK 019525, P50‐HL‐083799
Behavioural measures of nutrition related cognitive development in rural Gambia: studies from birth to 24 months of age (389.1)
Authors: Lloyd‐Fox Sarah , Halliday Drew , Maris Helen , Begus Katarina , Darboe Momodou , Prentice Andrew , Moore Sophie , Elwell Clare 
Published: June 2021

The Mullen Scales of Early Learning is a developmental assessment battery which can be administered from birth to five years of age to separately assess gross motor, fine motor, receptive language, expressive language, and visual receptive abilities. Scores for each subscale as well as an overall composite score are typically computed based on a comparison to Western norms. The aim of this work was to adapt the Mullen Scales for use at a field station in rural Africa as an assessment tool for cognitive function in nutrition based studies. We also examine associations between behavioural performance and anthropometric growth indices in young infants.A committee of native, dual‐language speakers and trained Mullen administrators reviewed and adapted the Mullen assessment for use in The Gambia. Adaptations included the linguistic translation of the item‐by‐item verbal prompts and the substitution of culturally inappropriate stimuli.We studied infants longitudinally at two time points between the age of 9‐17 months, and a separate group of toddlers at 18‐24 months of age. In addition to behavioural assessment, we collected anthropometric measurements and generated z‐scores based on WHO standards. An analysis of the relationship between growth and cognitive development revealed several significant associations over the first two years of life; in particular there were significant correlations with the language subscales. These results suggest that early language development is associated with growth markers in Gambian infants. The trajectories of several growth measures appear to decline steadily across the first 2 years of life, with associations to impaired behavioural performance already apparent from around the first year. These associations are difficult to examine in earlier infancy as the efficacy of behavioural measures at this age is limited. Optical imaging may be a viable solution to this problem, by providing an objective measure of cognitive function from birth.Grant Funding Source: Bill and Melinda Gates Foundation
Multiple micronutrient powders reduce stunting and anemia and improve language development among full‐term low birth weight children in Bangladesh (389.3)
Authors: Shafique Sohana , Singla Daisy , Aboud Frances , Jolly Saira , Zlotkin Stanley 
Published: June 2021

Objective: Explore efficacy of 22‐element micronutrient powders (MNP) plus nutrition, health and hygiene education (NHHE) to reduce stunting and anemia, and improve mental development among low birth weight (LBW) infants. Methods: Prospective community‐based cluster‐randomized trial, conducted among 244 full‐term LBW infants from 6‐12 months (mo) in rural Bangladesh. A total of 24 clusters were randomly assigned to two groups: i) NHHE plus MNP (to be provided with available complementary food); ii) NHHE only. Capillary blood was collected at 6 and 12mo using HemoCue. At ~18mo cognitive and language scores of children were assessed using Bayley Scales of Infant and Toddler Development III (n=186). Results: At 12 mo, compared to ‘NHHE only’, infants in ‘NHHE+MNP’ had significantly lower proportion of stunting (55.9% vs 33.6%, p<0.001) and anemia (23.9% vs 11.7%, p<0.001). Mean Hb concentration in the ‘NHHE+MNP’infants increased from 93.8±10.8 g/L at 6mo to 109.8±12.3 g/L at 12mo (p<0.05), whereas no such difference was found in ‘NHHE only’ group. Expressive language scores were significantly higher among ‘NHHE+MNP’ compared with ‘NHHE only’ (p<0.01; d=0.45). There were no differences between groups on cognitive or receptive language scores. Conclusion: Use of broad range micronutrient powders effectively reduce stunting and anemia and improve expressive language among term LBW children.Grant Funding Source: Bill & Melinda Gates Foundation to FHI 360, through the Alive & Thrive Small Grants Program managed
Lycopene and its metabolite apo‐10’‐lycopenoic acid suppressed high‐fat diet‐induced hepatic steatosis in beta‐carotene‐9’,10’‐oxygenase knockout mice (39.3)
Authors: IP Blanche , Liu Chun , Smith Donald , von Lintig Johannes , Wang Xiang‐Dong 
Published: June 2021

Prevalence of non‐alcoholic fatty liver disease is associated with the current obesity epidemic. Lycopene (LYC), which can generate apo‐10’‐lycopenoic acid (APO10LA) endogenously by beta‐carotene‐9’,10’‐oxygenase (BCO2), has been shown to modulate adipose and hepatic lipid metabolism. We examined whether BCO2 is essential for LYC’s biological effects. 12‐week supplementation of either LYC (100 mg/kg diet) or APO10LA (10 mg/kg diet) inhibited high‐fat diet (HFD)‐induced hepatic steatosis (by 77% vs 63% respectively) in BCO2‐knockout (BCO2‐KO) mice. APO10LA‐mediated steatosis suppression was associated with up‐regulated hepatic sirtuin 1 protein expression, and reduced de novo lipogenic markers (Scd1 gene; AMPK, ACC phosphorylation). These APO10LA‐mediated effects were absent in the LYC group. Intriguingly, LYC induced gene expression involved in fatty acid (FA) uptake (Lpl, Fatp4), FA β‐oxidation (Pparα, Lcad), and mitochondrial uncoupling (Ucp3) in mesenteric adipose tissue (MAT), and these LYC‐mediated effects were not present in APO10LA‐fed mice. Importantly, MAT Lpl and Ucp3 expressions were negatively correlated with hepatic steatosis, suggesting that LYC may reduce FA delivery from MAT to the liver. Taken together, this data provided novel insights that LYC and APO10LA may inhibit HFD‐induced steatosis in BCO2‐KO mice through differential mechanisms.Grant Funding Source: USDA/ARS grant 1950‐51000‐074S
Using verbal protocol to examine the comprehension and use of nutrition facts tables among young Canadians (390.8)
Authors: Shen‐Tu Grace , Hobin Erin , Sheeshka Judy , O'Brien Mary , McVey Gail , Hammond David 
Published: June 2021

OBJECTIVES: To explore how young Canadians engage with, understand, and use serving size and %DV information on current and modified Nutrition Facts Tables (NFts).METHODS: 26 participants aged 16‐24 years were recruited. Participants were randomly assigned to two NFts, one with high (蠅15%DV) and one with low (≤5%DV) sodium amount, altered to one of the 6 conditions: 1) Current NFts; 2) Standardized serving sizes (SSS); 3) High/Low (H/L) descriptors beside % Daily Value (%DV) for negative nutrients; 4) SSS + H/L descriptors; 5) H/L and color beside %DV; and 6) SSS + H/L and color. Participants completed a skill‐based questionnaire using the “think aloud” technique. Content analysis was used to examine how participants interpret, define, compare, and manipulate information in NFts.RESULTS: Exploration of participants’ thought processes identified barriers to understanding and using the current NFt. The barriers include failure to understand %DV, difficulty in manipulating %DV to compare nutrients across various serving sizes, and confusion about how to use NFt to choose foods. Analysis also revealed that the barriers mentioned above can be addressed by standardizing serving sizes on NFts and adding simple descriptors and/or colors to %DV information.CONCLUSIONS: SSS and H/L descriptors or color coded %DV information assists young people in understanding and using NFts when comparing and choosing foods.
Children’s intake of candy while in the absence of hunger exceeds USDA SoFAS limits (47.4)
Authors: Rollins Brandi , Savage Jennifer , Birch Leann 
Published: June 2021

Children’s intake of candy has increased over the past three decades, and is a source of added sugars and empty calories in middle childhood. However, little is known about the factors that influence children’s intake of candy. We examined children’s (ages 5‐8) intake of candy while in the absence of hunger in a laboratory setting, and evaluated individual differences in children’s candy intake. Children (n=66) were provided with a standard lunch consisting of a sandwich, milk, and apple slices; following lunch, each child self‐reported on their hunger level, and if not hungry, they were provided with free access to11 types of candy (e.g. solid chocolate bars, lollipops). Children’s height/weight were measured. On average, children consumed 198 kcals (SD = 118.8; range 0 to 464) of candy following a standard lunch, amounting to ~15.2% of the USDA estimated calorie needs for the average sedentary 4‐8 year old. Children’s energy intake from chocolate candies (M=102.3, SD=101.1; range 0 to 385) and non‐chocolate candies (M=96.7, SD=72.9; range 0 to 332) did not differ. In addition, no differences were observed by child gender, age, or BMI. Overall, our results indicate that children’s intake of candy in a free access condition and while in the absence of hunger exceeds the maximum limit (8‐9%) suggested by the USDA for calories from solid fats and added sugars (SoFAS).Grant Funding Source: Supported by the National Confectioners' Association
Targeting of Lewis‐X‐containing glycans blocks PMN transepithelial migration and increases phagocytosis and degranulation (488.3)
Authors: Brazil Jennifer , Sumagin Ronen , Lee Goo , Forrest Osric , Cummings Richard , Parkos Charles , Louis Nancy , Louis Nancy 
Published: June 2021

The transepithelial migration (TEM) of neutrophils (PMN) is a histopathological hallmark of inflammatory bowel disease (IBD), yet the mechanisms controlling PMN TEM remain poorly defined. The fucosylated, terminal glycan determinant Lewis X (Lex), expressed on the glycans of PMN surface glycoproteins (including MAC‐1 and LFA‐1), has previously been implicated in adhesive interactions between PMN and endothelium. However, little is known about the role of Lex in PMN function following extravasation. Flow cytometry analyses revealed increased surface expression of Lex on human PMN following TEM, while immunohistochemistry demonstrated robust expression of PMN‐associated Lex within crypt abscesses in the colonic epithelium of individuals with IBD. Furthermore, engagement of Lex increased PMN adhesive interactions, both with other PMNs and with intestinal epithelial cells, blocking PMN chemotaxis and TEM. In addition to blocking PMN trafficking, targeting of Lex also altered post‐migratory PMN functions, increasing both PMN phagocytosis of Salmonella enterica and release of primary granules. Therefore, glycans expressing the Lex determinant represent a novel target for regulating both the trafficking of PMN into the intestinal lumen and PMN function. Further, given its robust expression in migrating PMN and during inflammation, Lex may be a rational target for modulating inflammation in IBD.Grant Funding Source: Supported by Crohn's & Colitis Foundation of America and National Institutes of Health
Enteric commensal bacteria activate formyl peptide receptor 1 to regulate intestinal epithelial homeostasis and wound repair (488.7)
Authors: Alam Ashfaqul , Leoni Giovanna , Jones Rheinallt , Nusrat Asma , Neish Andrew 
Published: June 2021

Mucosal homeostasis and wound repair require epithelial proliferation and migration. Gut commensal microbiota are essential for normal intestinal development, renewal and repair. N‐formyl peptide receptors (FPRs) are G protein coupled receptors that function as pattern recognition receptors. FPR ligands include an array of peptides, lipids and small molecules derived from bacteria and the host. Intestinal epithelial cells (IECs) express functional FPRs in the cell surface plasma membrane. Recently we demonstrated that Annexin A1 and specific gut microbiota stimulate epithelial FPRs to generate reactive oxygen species which modulate cell signaling pathways critical for IEC proliferation and migration. However, it is incompletely understood how FPR1 maintains homeostasis of the gut symbionts important for mucosal wound healing. Here, we studied composition of murine mucosa‐associated microbiota in intact epithelia and endoscopic wound beds by pyrosequencing. We identified that specific species of essential gut bacteria is associated with mucosal wound bed. We also observed that FPR1 maintains homeostasis of mucosa‐associated microbiota characterized by their enrichment, composition, and spatial localization with respect to IECs. These changes are also associated with alterations in the colonic firm mucin layer, increased epithelial permeability and defective mucosal wound healing in FPR1‐/‐ mice during chronic DSS‐induced colitis. In conclusion, our study highlights a role of FPR1 in mediating important host‐microbiota interactions controlling gut mucosal homeostasis and wound repair.Grant Funding Source: CCFA and NIH
Objective structured skill examination in physiology education (531.6)
Authors: Matsuo Osamu , Kawao Naoyuki , Tamura Yukinori , Okada Kiyotaka , Nagai Nobuo , Ueshima Shigeru 
Published: June 2021

We tested the efficacy of objective structured skill examination (OSSE) as a new and useful examination. The second grade students at Kinki University Faculty of Medicine were prospectively eligible. Students took problem‐based learning (PBL) tutorials in addition to classroom lectures and laboratory practice in each session. The sessions were on: cardiac, circulation, hematological, and renal systems. After all sessions, OSSE was performed to evaluate the students’ performance. The technical skills evaluated in OSSE were as follows: electrocardiogram recording, blood pressure measuring, use of centrifuge, pipette technique, hematocrit measurement, urinary specific gravity determination, and measurement of urine volume. One order sheet and the experimental apparatus for OSSE were positioned at each station and students terminate the maneuver in 2 min. The score from OSSE was compared to that from the conventional evaluation. Significant positive correlation was not observed. More than half of the students considered OSSE to be meaningful. In conclusion, we developed a new structured examination to objectively assess the students' technical skills in laboratory practice.Grant Funding Source: None
Transitions in teaching: he experiences of basic scientists changing to an integrated anatomy curriculum (532.5)
Authors: Hopkins Robin 
Published: June 2021

Objective: The purpose of this study was to understand what the experience of transitioning to an integrated curriculum is like for anatomy educators with a basic science background, and to interpret what it means for their teaching.Methods: Lillian Douglas School of Medicine (pseudonym) was used as a case study of an anatomy program that has successfully transitioned to teaching anatomy in a clinically relevant way. A phenomenological approach was used to explore what it was like for basic scientists to change to teaching in an integrated curriculum. The primary investigator spent one month with the program during which she interviewed participants and observed lectures and labs. Data was analyzed using the reiterative cycle of hermeneutics.Findings: Using Daniel Pratt’s General Model of Teaching as a conceptual framework, transitioning to an integrated curriculum entailed a shift in the elements of teaching from emphasis on the teacher and content to students and the context of clinical practice. The foregrounding of students and context included both a change in content in terms of clinical cases, and a change in teaching towards a more student centered “Socratic” approach. These changes involved collaborating with physicians and pedagogical experts respectively, as well as ceding control in terms of deciding what to include in the course and how they would go about teaching it.Grant Funding Source: Supported by the Social Sciences and Humanities Research Council of Canada