bluuebunny/crossref_metadata_2025 huggingface dataset:
Low birth weight and its associated biopsychosocial factors over a 19-year period: findings from a national cohort study
Authors: Bizuayehu Habtamu Mellie , Harris Melissa L , Chojenta Catherine , Forder Peta M , Loxton Deborah
Published: March 2021

Background

In Australia, 6.7% of babies (5.2% for singletons) are born low birth weight (LBW), and over the past decade, this figure has increased by 8%. Evidence regarding LBW has largely come from hospital-based cross-sectional studies, which are not representative, lack temporality and do not examine the potential predictors of LBW using a comprehensive theoretical framework. This study, therefore, examined predictors of LBW within a biopsychosocial framework, using a community-based representative prospective cohort with 19 years of data.

Methods

The study included 11 854 singleton babies born to 5622 women from the 1973 to 1978 cohort of the Australian Longitudinal Study on Women’s Health.

Results

Among 5622 first births, 310 (5.5%) were reported as LBW. Maternal risk factors included pre-pregnancy underweight (aOR = 2.27, 95% CI: 1.43–3.62), chronic diabetes (aOR = 2.38, 95% CI: 1.14–4.95), gestational diabetes (aOR = 1.93, 95% CI: 1.27–2.94), chronic hypertension (aOR = 2.23, 95% CI: 1.50–3.33) and gestational hypertension (aOR = 2.44, 95% CI: 1.78–3.36). Among all births (N = 11 854), the overall LBW rate was 3.8% with a recurrence rate of 4.8%. Identified risk factors included menarche before 12 years (aOR = 1.57; 95% CI: 1.17–2.11), pre-pregnancy underweight (aOR = 2.25, 95% CI: 1.46–3.45), gestational diabetes (aOR = 1.74, 95% CI: 1.16–2.59), chronic hypertension (aOR = 2.01, 95% CI: 1.40–2.90) and gestational hypertension (aOR = 2.81, 95% CI: 2.05–3.84). LBW was less likely for second births (aOR = 0.39, 95% CI: 0.31–0.50) and third/above births (aOR = 0.49, 95% CI: 0.35–0.67) compared with the first births.

Conclusion

Increased nutrition counselling/supplementation for underweight women and interventions aimed at chronic disease prevention and management by using a multi-sectoral approach may be the key to the prevention of LBW.
Characterization of the binding motif for the T3SS master regulator LcrF in Yersinia pseudotuberculosis
Authors: Liu Luyi , Huang Shaojia , Fei Keke , Zhou Wei , Chen Shiyun , Hu Yangbo
Published: March 2021

LcrF is the master regulator that positively regulates the Ysc type III secretion system (T3SS) in Yersinia and shares a high similarity with the DNA-binding domain of the T3SS master regulator ExsA in Pseudomonas aeruginosa. Based on these features, bioinformatics analysis has predicted a putative LcrF-binding site in its target promoters. Here, we experimentally characterized its binding motif. An adenine-rich LcrF-binding region in the lcrG promoter sequence, a typical regulatory target of LcrF, was first confirmed. To obtain detailed information, this binding region was cloned into a synthetized promoter and mutations in this region were further constructed. We demonstrated that the 5’-AAAAA-n5-GnCT-3’ sequence is required for LcrF regulation and this motif is strictly located 4-bp upstream of a noncanonical promoter, in which the -35 and -10 elements are separated by a 21-bp spacer. Consistently, the putative binding motif was found in promoters of nine T3SS related operons or genes positively regulated by LcrF. Transcriptome analysis further confirmed that LcrF specifically activates T3SS genes in Yersinia. Collectively, our data suggest that LcrF has evolved to be a specific T3SS activator with a stringent sequence requirement for transcriptional regulation.
The Physiological Conundrum That is the Domestic Dog
Authors: Jimenez Ana Gabriela
Published: March 2021

Synopsis

Across Mammalia, body size and lifespan are positively correlated. However, in domestic dogs, the opposite is true: small dogs have longer lives compared with large dogs. Here, I present literature-based data on life-history traits that may affect dog lifespan, including adaptations at the whole-organism, and organ-level. Then, I compare those same traits to wild canids. Because oxidative stress is a byproduct of aerobic metabolism, I also present data on oxidative stress in dogs that suggests that small breed dogs accumulate significantly more circulating lipid peroxidation damage compared with large breed dogs, in opposition to lifespan predictions. Further, wild canids have increased antioxidant concentrations compared with domestic dogs, which may aid in explaining why wild canids have longer lifespans than similar-sized domestic dogs. At the cellular level, I describe mechanisms that differ across size classes of dogs, including increases in aerobic metabolism with age, and increases in glycolytic metabolic rates in large breed dogs across their lifespan. To address potential interventions to extend lifespan in domestic dogs, I describe experimental alterations to cellular architecture to test the “membrane pacemaker” hypotheses of metabolism and aging. This hypothesis suggests that increased lipid unsaturation and polyunsaturated fatty acids in cell membranes can increase cellular metabolic rates and oxidative damage, leading to potential decreased longevity. I also discuss cellular metabolic changes of primary fibroblast cells isolated from domestic dogs as they are treated with commercially available drugs that are linked to lifespan and health span expansion.
Parental income and mental disorders in children and adolescents: prospective register-based study
Authors: Kinge Jonas Minet , Øverland Simon , Flatø Martin , Dieleman Joseph , Røgeberg Ole , Magnus Maria Christine , Evensen Miriam , Tesli Martin , Skrondal Anders , Stoltenberg Camilla , Vollset Stein Emil , Håberg Siri , Torvik Fartein Ask
Published: March 2021

Background

Children with low-income parents have a higher risk of mental disorders, although it is unclear whether other parental characteristics or genetic confounding explain these associations and whether it is true for all mental disorders.

Methods

In this registry-based study of all children in Norway (n = 1 354 393) aged 5–17 years from 2008 to 2016, we examined whether parental income was associated with childhood diagnoses of mental disorders identified through national registries from primary healthcare, hospitalizations and specialist outpatient services.

Results

There were substantial differences in mental disorders by parental income, except for eating disorders in girls. In the bottom 1% of parental income, 16.9% [95% confidence interval (CI): 15.6, 18.3] of boys had a mental disorder compared with 4.1% (95% CI: 3.3, 4.8) in the top 1%. Among girls, there were 14.2% (95% CI: 12.9, 15.5) in the lowest, compared with 3.2% (95% CI: 2.5, 3.9) in the highest parental-income percentile. Differences were mainly attributable to attention-deficit hyperactivity disorder in boys and anxiety and depression in girls. There were more mental disorders in children whose parents had mental disorders or low education, or lived in separate households. Still, parental income remained associated with children’s mental disorders after accounting for parents’ mental disorders and other factors, and associations were also present among adopted children.

Conclusions

Mental disorders were 3- to 4-fold more prevalent in children with parents in the lowest compared with the highest income percentiles. Parents’ own mental disorders, other socio-demographic factors and genetic confounding did not fully explain these associations.
The Association of Coronavirus Disease 2019 Risk Perception, County Death Rates, and Voluntary Health Behaviors Among United States Adult Population
Authors: Elharake Jad A , Shafiq Mehr , McFadden SarahAnn M , Malik Amyn A , Omer Saad B
Published: March 2021

Background

The coronavirus disease 2019 (COVID-19) pandemic continues to adversely impact the United States socially, culturally, and economically. The purpose of this study was to understand the relationship between COVID-19 county death rates, risk perception, and US adults’ voluntary behaviors—particularly physical distancing.

Methods

Data were collected from CloudResearch/Qualtrics, Johns Hopkins University, the American Community Survey, and SafeGraph.

Results

Our results indicated that higher COVID-19 county death rates were associated with higher risk perceptions, leading to greater time spent at home.

Conclusions

These findings will help public health officials identify strategies that best encourage voluntary health behaviors to help curb the spread of COVID-19.
A1 F4/80+LY6CHI MACROPHAGES ARE KEY TO CANCER INITIATION IN COLITIS
Authors: Shin A E , Good H J , Tesfagiorgis Y , Zhang L , Kerfoot S , Sherman P M , Wang T C , Howlett C J , Asfaha S
Published: March 2021

Background

Colorectal cancer (CRC) is the third leading cause of cancer death, with a major risk factor being chronic inflammation. Thus, patients with inflammatory bowel disease (IBD) are at an increased risk of CRC. Despite the clear association between inflammation and cancer, the mechanism by which colitis leads to CRC is still not well understood.

Aims

In this study, we aim to explore the mechanism by which inflammation contributes to the initiation of colitis-associated cancer (CAC). We hypothesize that dextran sodium sulfate (DSS)-induced colitis leads to the infiltration of a specific immune cell type associated with tumorigenesis.

Methods

Following an injection of azoxymethane (AOM), mice were treated with the colitis-inducing agents DSS, trinitrobenzene sulfonic acid (TNBS), oxazolone (oxa), Citrobacter rodentium, or Doxorubicin (Doxo). The tumor studies were repeated using our published Cre-dependent murine model of CAC. To generate tamoxifen-inducible Cre transgenic mice that allow for Dclk1+ cell lineage tracing and cell-specific knock-out of the tumor suppressor adenomatous polyposis coli (APC), we crossed our Dclk1CreERT2 mice to both ROSA26tdTomato and APCfl/fl mice (Dclk1/APCfl/fl).

Results

Treatment with DSS, TNBS, oxa, C. rodentium, or Doxo induced colonic inflammation as detected by increased myeloperoxidase (MPO) activity and histologic analysis. DSS administration led to colonic tumors, whereas TNBS, oxa, C. rodentium, or Doxo did not lead to tumorigenesis up to 52 weeks following colitis induction. Upon flow cytometric analysis of several types of immune cells in the colonic tissue, we observed no difference in the number of T and B cells between mice treated with various colitis inducing agents. We did, however, detect significantly increased levels of Ly6G+ neutrophils and F4/80+Ly6Chi macrophages in the DSS-treated mice when compared to mice in the other models of colitis. mRNA and protein array analyses of the colonic tissue, as well as analysis of the RNA-seq data from 206 UC patients (GSE109142), revealed upregulated expression of genes associated with macrophages and neutrophils. Addition of macrophage-produced cytokines, such as IL-1β, TNF-α, or IL-6, induced lineage tracing of Dclk1+ tuft cells in intestinal organoids. Clodronate liposome-mediated depletion of F4/80+Ly6Chi macrophages significantly reduced the number of colonic tumors but did not affect tumor size in Dclk1/APCfl/fl mice.

Conclusions

Our data suggest that infiltration of F4/80+Ly6Chi macrophages, unique to DSS-induced colitis, leads to colonic tumor formation. This demonstrates that specific immune cell types, rather than the presence of colonic inflammation, plays an important role in the initiation of CAC.

Funding Agencies

CAG, CIHR
A13 A HIGH SALT DIET SYNERGIZES WITH UC MICROBIOTA TO INDUCE A PROINFLAMMATORY IMMUNE TONE IN IMMUNOCOMPETENT GNOTOBIOTIC MICE
Authors: Santiago Badenas A , Hann A , Galipeau H J , Constante M , Bercik P , Verdu E
Published: March 2021

Background

The exact cause for inflammatory bowel disease (IBD) is unknown, however, there is consensus that a combination of genetic, environmental, and immune factors, participate in its pathogenesis. Recently, high salt diet (HSD) has been shown to increase the severity of experimental colitis through depletion of lactobacilli in specific pathogen-free mice. However, whether HSD-microbiota interaction occurs in mice colonized with microbiota from patients with IBD, is unknown.

Aims

Our aim was to determine whether mice colonized with microbiota from patients with active ulcerative colitis (UC), one of two forms of IBD, develop more severe inflammation when fed a HSD.

Methods

10–15 week-old germ-free C57BL/6 mice were colonized with fecal microbiota from a healthy control (HC, n=13) or from a patient with UC experiencing a flare (UC, n=13). Colonized mice were housed in ISO positive cages (Techniplast) in a gnotobiotic facility during the experiment. For each group, half of the mice were kept on a control diet (7004, Teklad) and the other half were fed a HSD (7004 supplemented with 4% NaCl) plus 1% NaCl in drinking water for 3 weeks. At sacrifice, colon tissue was collected for histological analysis, RNA sequencing, and flow cytometry. Fecal samples were collected for lipocalin-2 determination.

Results

Colonic polymorphonuclear (PMN) cells were higher in UC compared with HC mice, regardless of diet (p<0.01). In mice fed HSD, UC mice also had higher PMN cell counts than HC mice (p<0.001). Administration of HSD to UC, but not to HC mice, also increased the proportion of α4+IFNg-producing T cells in the colonic lamina propria, compared with UC mice fed control diet (p<0.01). This was paralleled by higher fecal lipocalin-2 in UC mice fed HSD compared with control diet (p<0.05). Targeted analysis of RNA sequencing data revealed that 7 genes, mainly related to the JAK/STAT pathway (i.e., Stat2, Tyk2, Tlr7) were differentially expressed (p≤0.05) between HC and UC mice fed the control diet. A different gene expression signature was found in mice fed HSD compared with control diet, with an increase in proinflammatory genes in UC colonized mice compared to HC colonized mice, such as Il12a and Il6 (p<0.05).

Conclusions

Immunocompetent mice colonized with microbiota from a UC patient in flare spontaneously developed a proinflammatory immune tone, which was exacerbated by HSD. The different pattern of gene induction observed in mice colonized with the microbiota from the same UC donor, but fed HSD, suggests independent and synergistic pathways conducive to inflammation. Future studies will explore the preclinical therapeutic effect of novel drug candidates for the inhibition of such pathways.

Funding Agencies

CCC
A22 PREVALENCE OF IRON DEFICIENCY AND SUPPLEMENTATION PRACTICES FOR PATIENTS ON HOME PARENTERAL NUTRITION
Authors: Russell L , Mangat R , Plant J , Hansen S , Armstrong D , Pinto-Sanchez M I
Published: March 2021

Background

Iron deficiency (ID) is common in patients receiving parenteral nutrition (PN), likely due to a lack of iron in the PN formula. There is no clear consensus on how often serum iron should be tested or iron supplementation should be given, at which dose or route, in patients on long-term PN. Within the Hamilton Health Sciences (HHS) home PN (HPN) program, the prevalence of ID or iron deficiency anemia (IDA) is unknown. This knowledge will contribute to better iron prescribing practices with ultimate benefit on patient’s health.

Aims

To assess the prevalence of ID and IDA in patients enrolled in the HHS HPN Program. The secondary aim was to assess supplementation practices for patients enrolled in the HPN program according to gastrointestinal(GI) diagnosis and duration on PN.

Methods

We conducted a retrospective study including consecutive adult patients enrolled in the HHS-HPN program from January 2015 to November 2020. We collected data on demographics (age, sex, and GI diagnosis), iron supplementation (dose, duration, and route), and information related to iron-deficiency (hemoglobin, serum iron, ferritin, TIBC, and folate) at pre-set intervals (enrollment, 3, 6, 12, 18, 24, 30, 36, 48, 60 months) and last measured. ID was defined as ferritin ≤45μg/L or serum iron ≤9μmol/L. IDA was defined as hemoglobin <130g/L in men or <120g/L in women in the context of ID. Data were expressed as median (IQR) for continuous variables and n/N(%) for categorical variables. Chi2 was performed to assess differences between groups and logistic regression to assess predictors of ID and IDA. The analysis was conducted using SPSS software(v26).

Results

The analysis included 125 HPN patients (50 males, median age of 55 (40–65) years). Patients received PN for a median of 195 (83–521) days. The most common diagnoses were malignancy (36.8%) and inflammatory bowel disease (23.2%); the most common indications for HPN was short bowel (29.6%) and bowel obstruction (27.2%). Iron profiles were measured in 77% of patients. At enrollment, 42.2% of patients had ID and 38.9% had IDA. Only 13% of patients with ID and 22.8% with IDA had iron supplementation (Figure 1). A total of 38 patients received iron either oral or IV (oral=44.7% vs IV=55.3%; p=0.66). There was no correlation between low levels of serum iron or ferritin with iron supplementation (p=0.23, 0.45 respectively). Age, sex, diagnosis, or reason for PN did not correlate with ID or IDA at any time point.

Conclusions

Iron-deficiency and IDA are common in patients enrolled in the HHS HPN program independently of age, sex, diagnosis and reason for PN. Prospective studies are needed to implement the most effective way to ensure proper monitoring and treatment of iron deficiency in this population.

Funding Agencies

None
A37 EXPLORING THE PROTEOMICS DIFFERENCES IN CROHN’S DISEASE PATIENTS
Authors: Nogueira de Almeida L , Mainoli B , Filyk A K , Hirota S A , Lu C , Dufour A
Published: March 2021

Background

Canada has the highest prevalence rate of Crohn’s disease (CD) in North America. In Alberta, the yearly cost of anti-inflammatory drugs can be more than $25,000 per person; however, half of the patients do not respond to medication. CD is characterized by lesions in the small intestine due to inflammation, promoting diarrhea and abdominal pain. Prolonged chronic inflammation results in fibrotic strictures that are resistant to anti-inflammatory therapies and promote narrowing of the luminal space that ultimately require surgery. Currently, there is no biomarker to distinguish between the inflammatory or stricturing phenotype.

Aims

AIM 1: Profile serum samples from CD patients using a label-free shotgun-proteomics.

AIM 2: Identify signatures and biomarkers that distinguish inflammatory and fibrotic strictures using a bioinformatics approach.

Methods

Serum samples from 15 CD patients with strictures and 15 CD patients without strictures (inflammatory phenotype), as diagnosed by ultrasound imaging, were analyzed by a standard shotgun-proteomics approach. Briefly, 200 µg of serum proteins were processed in a label-free protocol in combination with the filter-aided sample preparation (FASP) method. Liquid chromatography-tandem mass spectrometry was performed on an Orbitrap Fusion Lumos. Protein identification was accomplished by MaxQuant at a 1% false-discovery rate. Statistical significance was determined by the MSstats package, in the R software. To identify the biological significance of disturbed pathways, it was characterized by the protein-protein interactions and pathway enrichment analysis using String-DB and Metascape.

Results

It was identified a statistically significant protein panel between the two phenotypes. Proteins identified in the strictured group include JAK1 (Tyrosine-protein kinase), CD5 antigen-like protein (regulates inflammatory gene expression in Th17 cells), and neogenin (cell adhesion). Of the inflammatory patients, there was a significant elevation of PFK/FBPase 2 (synthesis and degradation of fructose 2,6-bisphosphate), vinculin (cell-matrix adhesion) and MMP-16/MT3-MMP (matrix metalloproteinase).

Conclusions

The identification of a distinct signature between both phenotypes provide important biological information about the disease progression and are a good sign that a biomarker discovery platform will be capable to differentiate between inflammatory and fibrostenotic strictures from serum samples of CD patients.

Funding Agencies

CAG, CIHRNSERC
A47 SYNTHETIC HUMAN MILK OLIGOSACCHARIDES PREVENT EXPERIMENTAL NECROTIZING ENTEROCOLITIS VIA DIVERGENT TRANSCRIPTOMIC RESPONSES.
Authors: Wu R Y , Li B , Horne R , Ghamel A , Robinson S , Cadette M , Miyake H , Johnson-Henry K , Pierro A , Sherman P M
Published: March 2021

Background

Breastmilk reduces the risk of necrotizing enterocolitis (NEC) in preterm infants, but the bioactive components mediating this effect are not well understood. Human milk oligosaccharides (HMOs) reduce NEC both in humans and in relevant animal models. However, it is unclear if there are functional differences between individual oligosaccharides.

Aims

The objective of this study was to compare the intestinal transcriptome responses of individual HMOs using complementary in vitro and in vivo models of NEC.

Methods

RNA sequencing was performed on Caco-2Bbe1 gut epithelial cells after exposure to commercially-purified 2’-fucosyllactose (2’FL), 3-fucosyllactose, 6’-siallyllactose, lacto-N-tetraose (LNT) or lacto-N-neotetraose for 24hr at 37°C for 24 h (n=3). Signaling pathways were analyzed in murine- and human-derived NEC enteroids by qPCR. To validate these findings, five-day-old mouse pups were orally gavaged formula with or without individual HMOs, followed by NEC induction with hypoxia (5% O2, 95% N2) and lipopolysaccharide (4 mg/kg/day). Coded ileal sections (n=6–7/group) were analyzed for mucosal injury by histology, immune fluorescence, immunohistochemistry, and gene expression via qPCR.

Results

The HMO transcriptome clustered into divergent functional categories including metabolic process, protein processing and responses to external stimuli. Each synthetic HMO induced a unique transcriptome and exhibited varying effects on the intestinal epithelial functions and biological pathways. This was confirmed in the murine model of NEC, as both LNT and 2FL mitigated NEC injury with comparable recovery of intestinal cell proliferation (Ki67) and expression of stem cells (Lgr5+). Both qPCR and immunofluorescence staining showed differences between 2FL- and LNT-fed pups in host inflammatory and immune responses.

Conclusions

This study demonstrates that synthetic HMOs ameliorate intestinal injury in experimental NEC. However, the mechanisms by which individual oligosaccharides act on the intestine differ, suggesting that single synthetic HMOs may not fully recapitulate the benefits of pooled HMOs. Future studies will further delineate structure-function relationships of synthetic HMOs on host intestinal innate and adaptive immune responses.

Funding Agencies

CIHRFerring Canada Medical Student Research grant
A49 BUTYRATE PRESERVES THE EPITHELIAL MITOCHONDRIAL NETWORK DISRUPTED BY THE CROHN’S DISEASE PATHOBIONT ADHERENT-INVASIVE E. COLI
Authors: Hamed S , wang A , Shearer J , Shutt T , Mckay D M
Published: March 2021

Background

Mitochondria exist in a dynamic network that undergoes continuous cycles of fission and fusion that is tightly controlled. Mitochondrial dysfunction is implicated in several autoimmune and inflammatory diseases. Adherent-invasive E. coli (AIEC) is a pathogenic strain of bacteria associated with Crohn’s disease (CD), that can evoke pro-inflammatory responses. Data from our lab showed that AIEC (strain LF82) infection in gut epithelial cells (T84 human cell line) caused dramatic mitochondrial network fragmentation and loss of mitochondrial membrane potential. Short chain fatty acids (SCFA) produced by commensal bacteria in the gut have a wide range of benefits including enhancing mitochondrial biogenesis.

Aims

To determine (1) if sodium butyrate (NaB) treatment can protect against mitochondrial dysfunction induced by AIEC (strain LF82) infection in T84 epithelial cells and then (2) to identify the mechanism by which NaB restores mitochondrial functions.

Methods

We assessed changes in mitochondrial network morphology through confocal microscopy live cell imaging of mitotracker-stained T84 epithelial cells based on unbiased Hoechst-stained nuclei to select the field of view. The effect of NaB on the proliferation of bacteria and their invasion of T84-epithelia was assessed by growth curve analysis and bacterial internalisation assays. Finally, mRNA and protein expression of peroxisome proliferating activator receptor gamma co-activator 1 alpha (PGC1α), a regulator of mitochondrial biogenesis, were assessed by qPCR and Western Blot.

Results

We confirmed that AIEC infection (strain LF82, 108cfu, 4h) induces massive mitochondrial fragmentation in T84 cells (2x105). We also found that cotreatment of T84 cells with NaB (10mM) and LF82 showed increased percentage of fused mitochondrial networks compared to LF82-treated cells. This result was also seen in cells treated with mitochondrial uncoupler dinitrophenol (DNP; 0.1 mM, 2h) and NaB. Moreover, the protective effect of NaB was not related to inhibition of proliferation of the bacteria as we demonstrated that LF82 growth and its invasive phenotype was not compromised by NaB (3-20mM; 0-24hr). In agreement with the effect of LF82 on mitochondrial functions, LF82 significantly reduced PGC1α mRNA expression in T84 cells, that was prevented by co-treatment with NaB.

Conclusions

These data suggest the pathogen disruption of the epithelial mitochondrial network is a component of IBD; thus, identifying mitochondrial fission and fusion pathways as novel therapeutic targets to control enteric inflammation. The data underscore the complex interplay between bacteria and the epithelium, such that commensal organisms may preserve the mitochondrial network in the face of challenge from pathogens that seek to disrupt mitochondrial form and function

Funding Agencies

CIHR
A50 MODULATION OF GOBLET CELL ACTIVITY DURING GIARDIA DUODENALIS INFECTION: A ROLE FOR PAR2
Authors: Fekete E , Amat C B , Allain T , Hollenberg M , Mihara K , Chadee K , Buret A
Published: March 2021

Background

Giardia duodenalis has been shown to alter the structure of the intestinal mucus layers during infection via obscure mechanisms. We hypothesize that goblet cell activity may be disrupted in part due to proteolytic activation of protease-activated receptor 2 (PAR2) by Giardia proteases, resulting in disruption of mucus production and secretion by intestinal goblet cells.

Aims

Characterize alterations in goblet cell activity during Giardia infection, focusing on the roles of Giardia protease activity and PAR2.

Methods

Chinese hamster ovary cells transfected with nano-luciferase tagged PAR2 were incubated with Giardia NF or GSM trophozoites. Cleavage within the activation domain results in release of enzymes into the supernatant. Luminescence in the supernatant was measured as an indication of PAR cleavage by Giardia.

LS174T, a human colonic mucus-producing cell line, was infected with Giardia trophozoites (isolates NF, WB, S2, and GSM). Prior to infection, trophozoites were treated with E64, a broad-spectrum cysteine protease inhibitor, and LS174T were treated with a PAR2 antagonist, a calcium chelator, or an ERK1/2 inhibitor. Quantitative PCR (qPCR) was performed for the MUC2 mucin gene.

Wild-type (WT) and PAR2 knockout (KO) mice were infected with Giardia. Colonic mucus was stained using fluorescein-coupled wheat-germ agglutinin (WGA), and qPCR was performed for Muc2 and Muc5ac.

Results

Giardia trophozoites cleaved PAR2 within the N-terminal activation domain in a cysteine protease-dependent manner. Cleavage was isolate dependent, with isolates that show higher protease activity cleaving at a higher rate.

High protease activity Giardia isolates increased MUC2 gene expression in LS714T. This increase was attenuated by inhibition of Giardia cysteine protease activity, and by antagonism of PAR2, inhibition of calcium release, or inhibition of ERK1/2 activity in LS174T cells.

Both Muc2 and Muc5ac expression were upregulated in the colons of WT mice in response to Giardia infection, while in the jejunum Muc2 expression decreased and Muc5ac expression increased. In KO, no changes in gene expression were seen in the colon in response to Giardia infection, while in the jejunum, Muc2 expression was unchanged and Muc5ac expression decreased. Both WT infected and KO noninfected mice showed thinning of the colonic mucus layer compared to WT controls. There was some recovery in thickness in KO infected mice.

Conclusions

PAR2 plays a significant role in the regulation of mucin gene expression in mice and in a human colonic cell line. Results suggest that Giardia cysteine proteases cleave and activate PAR2, leading to calcium release and activation of the MAPK pathway in goblet cells, ultimately leading to altered mucin gene expression. Findings identify a novel regulatory pathway for mucus production by intestinal goblet cells.

Funding Agencies

CAG, CCC
A57 THE USE AND INTERPRETATION OF HLA-DQ2/DQ8 GENOTYPING BY PEDIATRIC GASTROENTEROLOGISTS
Authors: Moreau B , Robidoux E
Published: March 2021

Background

A recent classification of high and low risk alleles associated with celiac disease (CD) shows that the presence of a single allele (DQA1*05 or DQB1*02; coding together for HLA-DQ2), without a positive genotype (HLA-DQ2 and or HLA-DQ8), represents a risk of developing the disease.

Aims

The aim of this study is to evaluate the use and interpretation of the HLA-DQ2/DQ8 genotyping by pediatric gastroenterologists, as there is no study on the matter and the latest guidelines do not address this risk classification.

Methods

A web-based survey was sent by email to all NASPGHAN (North American society of pediatric gastroenterolgy, hepatology and nutrition) members.

Results

Results 294 pediatric gastroenterologists sent a complete survey. 86,1% use the HLA-DQ2/DQ8 genotyping according mainly to the NASPGHAN and ESPGHAN guidelines. The main indications considered were to exclude CD in a patient on a gluten-free diet with a resolution of his symptoms and in a seronegative patient with equivocal biopsies. A minority would consider the genotyping for screening high risk groups or for making a diagnosis in children with high specific CD antibodies and strong clinical suspicion without performing biopsies, as suggested by the ESPGHAN guidelines. The alleles associated with CD are not well known, but 76,7% the participants are aware of the risk classification. While only 62,8% have access to the complete genotype, 47,8% consider it useful. Nevertheless, 82,6% would still want to know the presence of a low risk allele.

Conclusions

The risk classification of alleles related to CD warrants a modification of the genotyping result with access to the alleles and an adaptation of the guidelines.

Funding Agencies

None
A60 SIGNIFICANCE OF IBD DIAGNOSIS IN THE BC COLON SCREENING PROGRAM
Authors: Bedi H K , Telford J J , Schaeffer D , Penner R M , Atkinson K , Fu Y , Wiesinger H , Rioux K P , Salh B
Published: March 2021

Background

There has been evidence of incidental inflammatory bowel disease (IBD) diagnosis in otherwise asymptomatic patients during colonoscopy to follow-up a positive fecal immunochemical test (FIT). Little is known about the significance of subclinical disease and its progression in this population.

Aims

To determine the incidence and outcome of subclinical IBD in a colon screening program. We hypothesize that the proportion of patients receiving biologic or surgical intervention would be low.

Methods

IBD cases were identified using the BC Colon Screening Program (BCCSP) database; pilot program at 3 sites from 01/2009–11/2013, and province-wide from 11/2013- 12/2017. Inclusion criteria: diagnosis of IBD at BCCSP colonoscopy performed for positive FIT. Exclusion criteria: prior IBD diagnosis, microscopic colitis. Data obtained through chart review included: demographics, endoscopy and histology reports, and medical/surgical treatment.

Results

Of 93,994 colonoscopies, 608 were diagnosed with IBD (0.65%) (Figure 1). Chart review of 245 cases at 10 institutions was performed. 65 patients were excluded. Of the 180 cases included, the average age at diagnosis was 59.6 years and 58.9% were male. 70.6% of patients were Caucasian, 12.2% were East Asian, and 7.8% South-east Asian. 49.4% were diagnosed with Crohn’s disease (CD), 33.9% with Ulcerative Colitis (UC), and 16.7% with indeterminate colitis, with a median follow-up of 25.5 months (0–85.9 months). 62.8% of patients received treatment, with 17.8% requiring biologic therapy, and 1.7% requiring surgical intervention.

Conclusions

This is the largest study assessing subclinical IBD in a colon screening program, with IBD incidence comparable to other publications in this population. However, the high proportion of patients diagnosed with CD is a novel finding. Also, subclinical IBD is not as benign as previously reported as nearly 20% of patients required biologics and/or surgical intervention.

Funding Agencies

None
A76 CLINICAL OUTCOMES, HEALTHCARE UTILIZATION AND COSTS AVOIDED WHEN ROUTINE GASTROENTEROLOGY REFERRALS ARE MANAGED IN PRIMARY CARE SUPPORTED BY CO-DEVELOPED CLINICAL CARE PATHWAYS
Authors: Qureshi A A , Belletrutti P J , Mazurek M S , Jelinski S , Maracle B , Heather G , Kaplan G G , Veldhuyzen Van Zanten S , Swain M , Novak K L
Published: March 2021

Background

The demand for gastroenterology (GI) care in Canada outstrips the supply. In the Calgary Zone, a Central Access and Triage (CAT) model is used as a single point of entry for most GI referrals. In collaboration with primary care, clinical care pathways (CCP) were co-developed and implemented in CAT to support care for common GI referrals in the Primary Care Medical Home (PCMH), avoiding specialty consultation/endoscopy.

Aims

To evaluate the re-referral rate, health outcomes, health system utilization (emergency department (ED) visits and hospitalizations) and costs avoided for referrals managed in the PCMH.

Methods

A prospective observational cohort study of patient referrals declined (closed) by CAT for one of seven indications supported with CCPs: chronic abdominal pain, chronic constipation, chronic diarrhea, dyspepsia, reflux disease, Helicobacter pylori, and irritable bowel syndrome (IBS). Patient clinical records were linked to healthcare administrative databases to extract data: CAT, electronic medical records, discharge databases, and physician billing claims. The Pampalon Deprivation Index evaluated socioeconomic status and education level. Costs according to Canadian Institute for Health Information were estimated for healthcare utilization, consultation and endoscopy.

Results

A total of 3435 referrals were closed for 3274 patients during the study period (July 1, 2018 to May 31, 2020) with dyspepsia being the most common indication (34%). The median age was 45 years, 66% were women and 43% of higher socioeconomic status. Re-referral to GI occurred in 12% leading to 414 endoscopies performed in 348 patients, the majority were normal (93.6%). Two diagnoses of colorectal adenocarcinoma were identified: 1 originally referred for dyspepsia with subsequent colonoscopy for FIT positivity and 1 initially referred for chronic diarrhea but later presented with hematochezia. Over one year, 11% of patients visited an ED yet less than half for the same indication (42.7%, 263/616 visits) with abdominal pain, dyspepsia, and IBS as most common reasons. There were 52 patients with 68 hospitalizations, but only 24% related to GI referral (constipation and abdominal pain). Estimated total costs avoided was $(CA)2,275,344; and with estimated healthcare utilization of $1,440,281, the net costs avoided was $1,477,237.

Conclusions

Innovative, collaborative strategies aimed to better match supple-demand disparity and improve appropriateness of specialty GI referrals are critical to improving timely patient care. Use of CCPs to support care in the PCMH is safe and reduces costs. Continued development of such supports is important to reduce avoidable healthcare utilization.

Funding Agencies

Health Innovation Implementation and Spread (HIIS) Fund
A80 IMPACT OF THE COVID-19 PANDEMIC IN IBD PATIENT CARE
Authors: Dahiya M , Olayinka L , Kaplan G G , Reeb L , Ma C , Panaccione R , Kroeker K
Published: March 2021

Background

The COVID-19 pandemic is affecting patients and healthcare providers worldwide. During the first wave of the pandemic, healthcare delivery shifted from in-person to virtual clinics. Non-urgent and some emergent procedures, including endoscopies, surgeries, and imaging, were delayed to limit the spread and divert resources to COVID-19.

Aims

To assess the impact of the COVID-19 pandemic in care to IBD patients

Methods

A survey study was conducted to assess the impact of the COVID-19 pandemic on IBD care. All patients had a virtual clinic appointment between March to July 2020 at either: University of Alberta Hospital or the University of Calgary Clinic. A section of the survey assessed patient experience of virtual clinics and delays in access to IBD care during the COVID-19 pandemic.

Results

A total of 1581 patients were contacted to complete the survey. 628 patients agreed to participate in the survey, however not all patients completed each component. The mean age of patients who participated in the survey was 48 years (SD = 15.19). 408 patients responded to satisfaction/future use questions: 84.3% (344) patients agree/strongly agree they were comfortable communicating to the physician using the remote system, 77.5% (316) of patients agree/strongly agree that virtual clinic is an acceptable way to receive healthcare services, 84.8% (346) of patients agree/strongly agree they would use virtual care services again, and 82.6% (337) agree/strongly agree they were satisfied with the telehealth system.

Additional challenges were reported by 228 patients. Fear and stress (infection risk/mental health concerns/unemployment) was reported by 57.4% (131) patients. Access to healthcare services, PPE, and community resources was a challenge experienced by 26.3% (60) patients. Additionally, 16.2% (37) patients experienced uncertainty around IBD-specific care, including procedures, treatments, labs, and medications.

Overall, 17.3% of patients reported some type of delay in care by July 2020. Table 1 shows the proportion of patients with a delay by type of care and the median delay: 5.7% of patients with IBD had surgery delayed by a median of 10 weeks (8–16 weeks).

Conclusions

While some delays in healthcare delivery occurred during the first wave of the pandemic, overall 82.7% of patients with IBD maintained their care without disruption. Sustaining healthcare delivery to the IBD community required adaptation to virtual care; however, patient satisfaction was overwhelming positive among patients with IBD.

Funding Agencies

None
A84 THE IMPACT OF GASTROINTESTINAL FOLLOW UP CARE ON HEALTHCARE UTILIZATION IN PATIENTS WITH EOSINOPHILIC ESOPHAGITIS (EOE).
Authors: Alazemi K , Alkhattabi M , Gregor J C
Published: March 2021

Background

EoE is an increasingly recognized gastrointestinal condition that causes significant morbidity ranging from dietary limitations to food impactions requiring emergency room visits. There are a variety of dietary, pharmacologic and endoscopic treatments available but most are more practically guided by a subspecialist familiar and experienced with the condition. There is a perception among some physicians that follow up is sporadic and may be related at least in part to patient compliance

Aims

To assess patients with EoE utilization of health care in LHSC

Methods

We used a retrospective cohort of patients diagnosed with EoE between July 2011 and June 2014 who met the traditional diagnostic criteria. As part of a quality improvement initiative, local follow up over the ensuing 5–7 years was tracked. The impact of follow up on subsequent healthcare utilization was analyzed.

Results

123 patients with biopsy confirmed EoE were analyzed. Follow up appointments were made for 114/123 (92%) patients. 55/123 (45%) had repeat elective endoscopy booked. Only 10/114 (8.7%) of initial appointments went unattended but 15/55 (27.2%) of the patients offered ongoing follow up failed to attend. There were no complications (ie. perforation or bleeding) attributable to any of the procedures. 5/123 (4%) patients required repeat emergency room endoscopy for food impaction. Two patients required this on multiple occasions. 4/5 patients requiring repeat emergency room endoscopy for food impaction had received some sort of follow up, although 4/5 of these had at least one missed appointment. 2/5 patients having emergency room endoscopy required overnight admission. There were no perforations in the cohort.

Conclusions

Patients with a confirmed diagnosis of EoE do have a risk of requiring subsequent emergency endoscopy for food impaction although it is not clear that scheduled follow up significantly reduces that risk. Contrary to the perception of some physicians, patients with EoE are very likely to attend their first follow up visit although the attrition rate for subsequent scheduled visits is not insignificant.

Funding Agencies

None
A87 HEALTHCARE PROVIDER SATISFACTION WITH VIRTUAL CARE DELIVERY IN ALBERTA DURING THE COVID-19 PANDEMIC.
Authors: Olayinka L , Kaplan G G , Reeb L , Panaccione R , Kroeker K
Published: March 2021

Background

In light of the COVID-19 pandemic, gastroenterologists in Alberta moved to virtual care for many clinic visits. As the public health situation evolves, it is important to evaluate provider satisfaction with virtual care during these unprecedented times.

Aims

To assess healthcare provider (HCP) satisfaction with virtual care during the COVID-19 pandemic.

Methods

We administered a 20-item satisfaction survey that assessed the usefulness, ease of use, interface qualities, reliability, and overall satisfaction with virtual care tools for the delivery of care to patients with gastrointestinal diseases. One hundred and twenty-five gastroenterologists in Alberta were invited to participate via email. We used a modified Telehealth Usability Questionnaire (TUQ) which was open for response from June 19-August 30, 2020.

Results

The overall response rate was 19% (24/125) with 46% female respondents. Most respondents worked in an academic facility (63%) and had been in practice for a mean duration of 12.3 years. Respondents were from seven facilities within the South, Calgary, Central and Edmonton health zones. Virtual care reported was a hybrid model consisting of telephone and in-person (54%) or telephone and video consults (42%). Although 90% indicated that virtual care tools improved access to healthcare, provided location flexibility and were appropriate to meet healthcare needs, only 42% agreed that it saved time. Inconclusive virtual consultations due to the absence of physical examination and missing lab values was reported by 75% and 33% of HCPs, respectively. Ninety-five percent of HCPs who used video conferencing found it simple, easy to learn and were able to become productive quickly with it. Over 60% of HCPs reported that virtual care (irrespective of the platform used) was not the same as in-person visits. The mean overall satisfaction for HCPs who rarely or never had virtual care prior to the pandemic, was 0.57 points higher than those who often provided virtual care (4.36 vs 3.79; 95% CI: 0.26–0.88, p=0.001). Overall, 88% of providers were satisfied with virtual care and all respondents were willing to use it again (Figure 1). Identified areas of concern included patient safety, patient education on best practices, adequate remuneration, additional administrative duties, and challenges with providing care for new patients on virtual platforms.

Conclusions

This survey of GI providers in Alberta showed high satisfaction and acceptance with virtual care. However, the majority reported it to be less reliable than in-person visits. Access to Alberta Netcare to view investigations was deemed valuable. Areas of concern that needs to be addressed include patient education on virtual care best practices and provider resources to assist with new consultations on virtual platforms.

Funding Agencies

None
A90 A PROPENSITY SCORE-MATCHED, STATE-LEVEL COMPARISON OF INPATIENT CIRRHOSIS OUTCOMES IN ENGLISH VS NON-ENGLISH SPEAKING PATIENTS
Authors: Sedarous M , Alayo Q , Subramanian K , Nwaiwu O , Okafor P N
Published: March 2021

Background

United States (US) citizens speaking a foreign language at home has increased by 192% from 1980 to 2018.

Aims

With the increase in multiculturalism and ongoing concerns for health disparities in the US, we sought to compare inpatient outcomes between non-English speaking and English-speaking patients with cirrhosis.

Methods

The 2013–14 Maryland State inpatient databases were used to compare inpatient outcomes in adult patients with cirrhosis. The analysis cohort was identified using a validated algorithm of ICD-9 codes. Cirrhosis patients were stratified based on primary language into non-English-speaking patients [NESP] vs English-speaking patients [ESP]. A 1:3 propensity score matching analysis based on possible confounders was used to finalize the analysis cohort. The primary outcome (all-cause in-hospital mortality) and secondary outcomes including 30-day all-cause readmission rates, length of stay, total hospitalization charges were then compared between groups.

Results

In the study period, 3,035 NESP vs 21,212 ESP discharges were identified. We matched 1,659 NESP with 4,928 ESP using a 1:3 algorithm. Table 1 highlights demographic data. In the unmatched analysis, all-cause mortality was higher in the ESP cohort compared to NESP (6.71% vs 5.73%, p=0.046). However, after propensity-matching, inpatient mortality rate became comparable between both groups (6.45% vs 6.51%, p=0.9). Thirty day all-cause readmission rates were also similar between ESP vs NESP (4.87% vs 4.28%, p=0.18). Median length of stay in the ESP group was 4 days (IQR 3–8) vs 5 days (IQR 3–7) in the NESP group, while median total charges in ESP were $55,984 (IQR $33,897-$98,679) compared to $61,262 (IQR $36,228-$$108,369) in NESP.

Conclusions

While significant differences in socioeconomic status and payer type exist between non-English and English speaking cirrhosis patients, these do not appear to negatively impact inpatient outcomes including all-cause inpatient mortality, 30-day readmission rates, length of stay, total hospital charges.

Funding Agencies

None