bluuebunny/crossref_metadata_2025 huggingface dataset:
“Glorious Mothers” and “Rational Women”: A Comparative Analysis of the Chinese and English Regulatory Models of Abortion
Authors: Cao Weiwei
Published: February 2020

Access to safe abortion is essential to satisfy women’s need for healthcare and control over their life choices. Modern regulation of abortion appears to be female friendly because it abandons the old oppressive appearance and wears a liberal face. By examining the images of “glorious mothers” and “rational women” constructed by the Chinese and English regulatory models of abortion through a feminist lens, this Article aims to offer a more critical response to the two jurisdictions. Furthermore, by comparing the two models of abortion law, the Article provides feminists and reformers with a chance to learn about each other’s experiences and different regulatory strategies. As a result, they will be able to view the merits and shortcomings of their national abortion law from a fresh angle. Finally, this comparative study offers a basis for feasible law reform proposals that would empower women in decision making concerning abortion.
DeepCPP: a deep neural network based on nucleotide bias information and minimum distribution similarity feature selection for RNA coding potential prediction
Authors: Zhang Yu , Jia Cangzhi , Fullwood Melissa Jane , Kwoh Chee Keong
Published: February 2020

The development of deep sequencing technologies has led to the discovery of novel transcripts. Many in silico methods have been developed to assess the coding potential of these transcripts to further investigate their functions. Existing methods perform well on distinguishing majority long noncoding RNAs (lncRNAs) and coding RNAs (mRNAs) but poorly on RNAs with small open reading frames (sORFs). Here, we present DeepCPP (deep neural network for coding potential prediction), a deep learning method for RNA coding potential prediction. Extensive evaluations on four previous datasets and six new datasets constructed in different species show that DeepCPP outperforms other state-of-the-art methods, especially on sORF type data, which overcomes the bottleneck of sORF mRNA identification by improving more than 4.31, 37.24 and 5.89% on its accuracy for newly discovered human, vertebrate and insect data, respectively. Additionally, we also revealed that discontinuous k-mer, and our newly proposed nucleotide bias and minimal distribution similarity feature selection method play crucial roles in this classification problem. Taken together, DeepCPP is an effective method for RNA coding potential prediction.
LYPD4, mouse homolog of a human acrosome protein, is essential for sperm fertilizing ability and male fertility†
Authors: Wang Dan , Cheng Liping , Xia Wenjuan , Liu Xiaofei , Guo Yueshuai , Yang Xiaoyu , Guo Xuejiang , Xu Eugene Yujun
Published: February 2020

Fertilization is one of the fundamental biological processes, but so far, we still do not have a full understanding of the underlying molecular mechanism. We have identified a human acrosome protein, LY6/PLAUR domain containing 4 (LYPD4), expressed specifically in human testes and sperm, and conserved within mammals. Mouse Lypd4, also specific to the testis and sperm, is essential for male fertility. LYPD4 protein first appeared in round spermatids during acrosome biogenesis and became part of acrosomes during spermatogenesis and in mature sperm. Lypd4 knockout mice are infertile with normal sperm number and motility. Mutant sperm, however, failed to reach oviduct during sperm migration inside the female reproductive tract, leading to fertilization failure and infertility. In addition, Lypd4 mutant sperms were unable to fertilize denuded egg via IVF (in vitro fertilization) but could fertilize eggs within intact Cumulus-Oocyte Complex, supporting an additional role in sperm-zona interaction. Out of more than five thousand spermatozoa proteins identified by mass spectrometry analysis, only a small subset of proteins (26 proteins) was changed in the absence of LYPD4, revealing a whole proteome picture of mutant sperm defective in sperm migration and sperm-zona binding. ADAM3, a key component of fertilization complex, as well as other sperm ADAM proteins are significantly reduced. We hence propose that LYPD4 plays an essential role in mammalian fertilization, and further investigation of its function and its interaction with other sperm membrane complexes may yield insights into human fertilization and novel strategy to improve IVF success.
MRS Shows Regionally Increased Glutamate Levels among Patients with Exhaustion Syndrome Due to Occupational Stress
Authors: Savic Ivanka
Published: February 2020

Despite the rapid increase of reports of exhaustion syndrome (ES) due to daily occupational stress, the mechanisms underlying ES are unknown. We used voxel-based 1H-MR spectroscopy to examine the potential role of glutamate in this condition. The levels of glutamate were found to be elevated among ES patients (n = 30, 16 females) compared with controls (n = 31, 15 females). Notably, this increase was detected only in the anterior cingulate and mesial prefrontal cortex (ACC/mPFC), and the glutamate levels were linearly correlated with the degree of perceived stress. Furthermore, there was a sex by group interaction, as the glutamate elevation was present only in female patients. Female but not male ES patients also showed an increase in N-acetyl aspartate (NAA) levels in the amygdala. No group differences were detected in glutamine concentration (also measured). These data show the key role of glutamate in stress-related neuronal signaling and the specific roles of the amygdala and ACC/mPFC. The data extend previous reports about the neurochemical basis of stress and identify a potential neural marker and mediator of ES due to occupational stress. The observation of specific sex differences provides a tentative explanation to the well-known female predominance in stress-related psychopathology.
Sweetness Enhancement by Aromas: Measured by Descriptive Sensory Analysis and Relative to Reference Scaling
Authors: Bertelsen Anne S , Mielby Line A , Alexi Niki , Byrne Derek V , Kidmose Ulla
Published: February 2020

Sweetness enhancement by aromas has been suggested as a strategy to mitigate sugar reduction in food products, but enhancement is dependent on type of aroma and sugar level. A careful screening of aromas across sugar levels is thus required. Screening results might, however, depend on the method employed. Both descriptive sensory analysis and relative to reference scaling were therefore used to screen 5 aromas across 3 sucrose concentrations for their sweetness-enhancing effects in aqueous solutions. In the descriptive analysis, samples with added vanilla, honey, and banana aroma were rated as significantly sweeter than samples with added elderflower or raspberry aroma at all sucrose concentrations. In relative to reference scaling, honey aroma significantly increased the sweet taste compared with samples with added elderflower or no aroma at low and medium sucrose concentrations. Banana and raspberry aromas also increased the sweet taste significantly compared with the sample with added elderflower aroma at medium sucrose concentration in the relative to reference scaling. This demonstrates that the cross-modal effects observed by the 2 methods were different. In terms of the methods applied, relative to reference scaling was generally found to result in a decrease in the measured sweetness enhancement by aromas. In the descriptive analysis, the cross-modal effect of aromas on sweet taste perception was found to be significantly higher at 2.5% and 5.0% w/w sucrose compared with 7.5% w/w sucrose. These results highlight the importance of considering how references are employed in sensory analysis and how they affect cross-modal interactions.
Zinc can counteract selection for ciprofloxacin resistance
Authors: Vos Michiel , Sibleyras Louise , Lo Lai Ka , Hesse Elze , Gaze William , Klümper Uli
Published: February 2020

Antimicrobial resistance (AMR) has emerged as one of the most pressing threats to public health. AMR evolution occurs in the clinic but also in the environment, where antibiotics and heavy metals can select and co-select for AMR. While the selective potential of both antibiotics and metals is increasingly well-characterized, experimental studies exploring their combined effects on AMR evolution are rare. It has previously been demonstrated that fluoroquinolone antibiotics such as ciprofloxacin can chelate metal ions. To investigate how ciprofloxacin resistance is affected by the presence of metals, we quantified selection dynamics between a ciprofloxacin-susceptible and a ciprofloxacin-resistant Escherichia coli strain across a gradient of ciprofloxacin concentrations in presence and absence of zinc. The presence of zinc reduced growth of both strains, while ciprofloxacin inhibited exclusively the susceptible one. When present in combination zinc retained its inhibitory effect, while ciprofloxacin inhibition of the susceptible strain was reduced. Consequently, the minimal selective concentration for ciprofloxacin resistance increased up to five-fold in the presence of zinc. Environmental pollution usually comprises complex mixtures of antimicrobial agents. In addition to the usual focus on additive or synergistic interactions in complex selective mixtures, our findings highlight the importance of antagonistic selective interactions when considering resistance evolution.
Pentadecanal and pentadecanoic acid coatings reduce biofilm formation of Staphylococcus epidermidis on PDMS
Authors: Ricciardelli Annarita , Casillo Angela , Corsaro Maria Michela , Tutino Maria Luisa , Parrilli Ermenegilda , van der Mei Henny C
Published: February 2020

Staphylococcus epidermidis is well known to be one of the major causes of infections related to medical devices, mostly due to its strong capacity to form device-associated biofilms. Nowadays, these infections represent a severe burden to the public health system and the necessity of novel antibacterial strategies for the treatment of these difficult-to-eradicate infections is urgent. The Antarctic marine bacterium Pseudoalteromonas haloplanktis TAC125 was found to be able to produce an anti-biofilm molecule, the pentadecanal, active against S. epidermidis. In this work, we modified one of the most widely used silicone-based polymers, polydimethylsiloxane (PDMS), by adsorption of pentadecanal and its most promising derivative, pentadecanoic acid, on the PDMS surface. The biofilm formation of S. epidermidis RP62A on both untreated and modified PDMS was performed in a parallel plate flow chamber system, demonstrating the capability of the proposed anti-biofilm coatings to strongly reduce the biofilm formation. Furthermore, drug-release capacity and long-term efficacy (21 days) were also proven for the pentadecanoic acid coating.
Sea surface network optimization for tsunami forecasting in the near field: application to the 2015 Illapel earthquake
Authors: Navarrete P , Cienfuegos R , Satake K , Wang Y , Urrutia A , Benavente R , Catalán P A , Crempien J , Mulia I
Published: February 2020

We propose a method for defining the optimal locations of a network of tsunameters in view of near real-time tsunami forecasting using sea surface data assimilation in the near and middle fields, just outside of the source region. The method requires first the application of the empirical orthogonal function analysis to identify the potential initial locations, followed by an optimization heuristic that minimizes a cost-benefit function to narrow down the number of stations. We apply the method to a synthetic case of the 2015 Mw8.4 Illapel Chile earthquake and show that it is possible to obtain an accurate tsunami forecast for wave heights at near coastal points, not too close to the source, from assimilating data from three tsunameters during 14 min, but with a minimum average time lag of nearly 5 min between simulated and forecasted waveforms. Additional tests show that the time lag is reduced for tsunami sources that are located just outside of the area covered by the tsunameter network. The latter suggests that sea surface data assimilation from a sparse network of stations could be a strong complement for the fastest tsunami early warning systems based on pre-modelled seismic scenarios.
Acute Pancreatitis in a Patient With Ulcerative Colitis on Vedolizumab
Authors: Lin Elissa , Katz Seymour
Published: February 2020

Vedolizumab is a humanized monoclonal antibody that is approved for treatment of patients with moderate to severe ulcerative colitis and is thought to be both safe and effective. We present a case of vedolizumab-associated acute pancreatitis in an ulcerative colitis patient.
Plasticity in dormancy behaviour of Calanoides acutus in Antarctic coastal waters
Authors: Biggs Tristan E G , Brussaard Corina P D , Evans Claire , Venables Hugh J , Pond David W
Published: February 2020

Copepods that enter dormancy, such as Calanoides acutus, are key primary consumers in Southern Ocean food webs where they convert a portion of the seasonal phytoplankton biomass into a longer-term energetic and physiological resource as wax ester (WE) reserves. We studied the seasonal abundance and lipid profiles of pre-adult and adult C. acutus in relation to phytoplankton dynamics on the Western Antarctic Peninsula. Initiation of dormancy occurred when WE unsaturation was relatively high, and chlorophyll a (Chl a) concentrations, predominantly attributable to diatoms, were reducing. Declines in WE unsaturation during the winter may act as a dormancy timing mechanism with increased Chl a concentrations likely to promote sedimentation that results in a teleconnection between the surface and deep water inducing ascent. A late summer diatom bloom was linked to early dormancy termination of females and a second spawning event. The frequency and duration of high biomass phytoplankton blooms may have consequences for the lifespan of the iteroparous C. acutus females (either 1 or 2 years) if limited by a total of two main spawning events. Late summer recruits, generated by a second spawning event, likely benefitted from lower predation and high phytoplankton food availability. The flexibility of copepods to modulate their life-cycle strategy in response to bottom-up and top-down conditions enables individuals to optimize their probability of reproductive success in the very variable environment prevalent in the Southern Ocean.
Resources
Authors: Gregoline Brenda
Published: February 2020

The Resources chapter of the 11th edition of the AMA Manual of Style includes updated information on general dictionaries, medical and scientific dictionaries, general style and usage guides, guides to medical/scientific style and usage, and resources on writing, as well as helpful sources for addressing ethical and legal concerns and questions related to peer review and illustrations/display of data. Also included are useful websites, guidelines developed by professional organizations, and current contact information for professional scientific writing, editing, and communications organizations and groups.
A17 ASSOCIATION BETWEEN HOST INFLAMMATION-RELATED PROTEOMICS AND GUT MICROBIOME IN HEALTHY FIRST-DEGREE RELATIVES OF CROHN’S DISEASE PATIENTS
Authors: Raygoza Garay J , Turpin W , Smith M , Goethel A , Guttman D S , Croitoru K
Published: February 2020

Background

Crohn’s disease (CD) is a chronic inflammatory condition of the gastrointestinal tract. It has been suggested that the cause of CD is due to microbial and environmental factors that induce an imbalance of the immune system in genetically susceptible individuals. The Genetic Environmental Microbial (GEM) Project is a prospective study of asymptomatic first-degree relatives (FDR) of CD patients, recruited to understand the biological and environmental determinants of disease development.

Aims

Here, we aim to define the relationships between the host inflammation-related proteomics and gut microbiome composition in a cohort of 320 healthy CD FDRs at the time of recruitment.

Methods

We measured 92 inflammation-related serum proteins using the Olink® ’Inflammation’ proteomics panel. Stool microbial composition was determined by sequencing the V4 region of the 16S rRNA. To assess the relationship between serum protein levels and the relative abundance of microbial taxa, we used a zero-inflated two-part regression model corrected for multiple-comparisons (significant association at p< 2.75 × 10–4).

Results

We found fifteen serum proteins that were each significantly associated with the relative abundances of one to five genera or families, depending on the analyte. Of particular interest to CD, the relative abundance of both TNF-β and LIGHT (TNFSF14) were negatively associated with the relative abundance of bacteria in the Parabacteroides genus. Both TNF-β and LIGHT are members of the Tumor Necrosis Factor (TNF) family of cytokines with roles in mucosal healing, IgA production, and in control of innate lymphoid cells (ILCs). These processes have been hypothesized to have critical roles in CD pathology. Interestingly, prior work also demonstrates that Parabacteroides distasonis enhanced colitis in a mouse model and was isolated from a gut wall-cavitating microlesion in a patient with severe CD. Other inflammation-related proteins with significant taxa associations include IL-2, IL-33, OSM, 4E_BP1, IL-1α, ARTN, AXIN1, and CDCP1.

Conclusions

This study highlights the associations between inflammation associated proteomics and gut microbial taxa in asymptomatic FDRs of CD patients. The mechanisms explaining this association will require further analysis.

Funding Agencies

CCC The Leona M. and Harry B. Helmsley Charitable Trust
A24 RATE OF GASTROINTESTINAL ENDOSCOPY USE AND CONCOMITTANT ANESHESIOLOGY ASSISTANCE AND PREDICTORS OF ANESTHESIOLOGY ASSISTANCE: A POPULATION-BASED ANALYSIS
Authors: Singh H , Derksen S , Sirski M , McCulloch S , Lix L M
Published: February 2020

Background

There are limited Canadian data on time trends of gastrointestinal endoscopy (GIE) use and concomitant anesthesiology assistance.

Aims

To test the time trends and variations in concomitant anesthesiology assistance during GIE in the central Canadian province of Manitoba.

Methods

Physicians claims reimbursement data from the provincial health ministry were used to ascertain upper & lower GIE procedures and anesthesiology assistance annually from 1984 to 2016. The annual provincial population was determined from health insurance registration files. Generalized linear models with generalized estimating equations were used to test the linear trend over time and differences amongst age groups, health regions and income quintiles. Logistic regression analysis with generalized estimating equations was used to assess predictors of anesthesiology use.

Results

410, 685 individuals had at least one procedure in the observation period. Approximately half of the procedures were performed outside the recommended CRC screening age group of 50–74 years, with 38% among those less than 50 years. The average annual rate of increase was 4.6% (95% CI 4.4–4.8%). The rate of increase stabilized among the > 75 years group over the last 5 years of the study. There were marked regional variation in GIE procedures, with the smallest increase in Winnipeg region (the largest urban region):2.9% (95%CI: 2.5–3.3) vs. 5.2% (95%CI: 4.8–5.6) in Southern Health; RR: 2.2(figure 1 A). There were no differences in GIE rates by income quintile. Similar patterns were seen in analysis stratified by upper and lower GIE. Concomitant anesthesiology use ranged from 1% in Winnipeg region to 80% in the southern rural region (figure 1B). In the logistic regression analysis, independent predictors of concomitant anesthesiology use in rural regions included younger age, female sex, lower income quintile, and higher comorbidities of patients, GP endoscopist, region of physician practice, and lower volume endoscopy physician.

Conclusions

Marked regional variations in GIE use and concomitant anesthesiology use were observed in a universal health care system. Efforts to standardize care are needed to reduce variations.

Funding Agencies

Manitoba Health
A27 INCREASING INCIDENCE OF COLORECTAL CANCER IN ADULTS UNDER AGE OF 50 IN ALBERTA
Authors: Liu E Y , Wong C
Published: February 2020

Background

Overall colorectal cancer (CRC) incidence has been decreasing in Canada since the early 2000s, most likely due to increased use of colorectal cancer screening for adults over the age of 50. However, the incidence of CRC may be rising in adults younger than age 50 both in Canada and the USA. The American Cancer Society in 2018 issued a qualified recommendation that people with an average risk of CRC should start screening at age 45. The burden of CRC in adults under the age of 50 is not well-characterized in Alberta.

Aims

The aim of this study is to determine the incidence trends in colorectal cancer in adults under the age of 50 compared to those over the age of 50 in Alberta.

Methods

This cohort study determined the incidence of colorectal cancer in patients under the age of 50 compared to those over the age of 50 reported to the Alberta Cancer Registry (ACR) from 2010 to 2017. Annualized percentage changes (APCs) in incidence rate were estimated using the Joinpoint Regression Program 4.7.0.0 (Nation Cancer Institute). APCs in relative risk of CRC in different age groups compared to the 50–74 age group were also estimated in the same methodology.

Results

From 2010 to 2017 there were 17167 incident cases of colorectal cancer. Of these, 92% were in adults over the age of 50 while 8% were in those under the age of 50. For adults under the age of 50, incidence of CRC increased from 6 to 7.2 per 100,000 with a mean annual percentage change of 2.58% between 2010 and 2017. This is in contrast to adults over the age of 50, where the incidence of CRC decreased from 170 to 128 per 100,000 with a mean annual percentage change of -1.64% from 2010 to 2015 and -9.42% from 2015 to 2017. Compared to the 50–74 age group, the average relative risk of CRC in the 46–49 age group is 0.26 with an annual increase of 0.55%; while in the 40–45 age group the average relative risk of CRC is 0.15 with an annual increase of 2.61%.

Conclusions

Similar to national incidence trends, the incidence of CRC in adults under the age of 50 is increasing in Alberta. Although the overall incidence in this population is relatively low, suspicion of CRC in adults under age 50 can help prevent delays in diagnosis.

Incidence of colorectal cancer in Alberta for adults under the age of 50 increased from 6 to 7.2 per 100,000 with a mean annual percentage change of 2.58% between 2010 and 2017.

Funding Agencies

None
A36 THE ROLE OF MICROBIAL INDOLE METABOLITES IN CONTROLLING INFLAMMATORY RESPONSES AND HEALING IN RESPONSE TO DSS-INDUCED COLITIS
Authors: Nieves K , Flannigan K L , Alston L , Thomson C , McCoy K , Mani S , Hirota S A
Published: February 2020

Background

Failure to resolve inflammation is often associate with the complications of Crohn’s Disease (CD). The pregnane X receptor (PXR), a xenobiotic receptor, is recognized for its role in suppressing inflammation and has recently been shown to influence fibrogenesis in the liver. In the intestine, PXR-signaling can be influenced by the microbial tryptophan metabolite indole-3- propionic acid (IPA), which can modulate intestinal inflammation, in turn influencing fibrogenesis, resolution and healing. This suggests that the gut microbiota could modulate mucosal homeostasis and resolution of inflammation via microbial metabolites

Aims

To understand and characterize the interplay between microbial complexity and the regulation of host inflammatory and healing responses, specifically focusing on the PXR and its microbial metabolite ligand IPA.

Methods

Intestinal inflammation was induced using DSS (1%, 1.5%, 2% and 3.5%) for 5 days followed by healing for 25 days in C57Bl/6 stably derived moderately diverse mouse microbiota 2 (sDMDMm2) colonized gnotobiotic and C57Bl/6 specific pathogen free (SPF) mice. Inflammation, architectural changes and fibrosis were assessed using Haemotoxylin and Eosin and Masson-Trichrome histological stains. Weight was recorded daily for the first 10 days and every other day after for 25 days, for a total of 30 days. Fecal lipocalin was quantified in samples collected throughout the study to assess inflammation. Innate immune cell influx was measured by flow cytometry, and the microbiota assessed via 16S rRNA sequencing.

Results

The gnotobiotic sDMDMm2 mice were exquisitely sensitive to DSS-induced colitis, exhibiting significantly increased mortality and morbidity at 2% and 3.5% w/v DSS compared to the SPF group. To elicit the same degree of disease to assess recovery, sDMDMm2 mice were exposed to 1.5% DSS and SPF mice to 3.5% DSS. Following 25 days recovery, sDMDMm2 colonized mice showed increased levels of fecal lipocalin 2, as compared to the SPF mice. DSS-treated sDMDMm2 mice supplemented with IPA during their recovery presented lower levels of fecal lipocalin, similar to colitic SPF mice. IPA supplemented sDMDMm2 mice also exhibited greater overall survival, with no significant differences in neutrophil count compared to mice given H20 during recovery.

Conclusions

A model system with a less complex microbiota (sDMDMm2) has a higher susceptibility to acute inflammation and a diminished capacity to resolve said inflammation. Addition of the microbial metabolite IPA normalized the recovery of the sDMDMm2 colonized mice, to a response indistinguishable from SPF mice, while also increasing survival. These data highlight the importance of microbial complexity in the regulation of intestinal mucosal homeostasis.

Funding Agencies

CAG, CCC, CIHR
A45 INFLAMMATION AND INTESTINAL PERMEABILITY IN PEDIATRIC SHORT BOWEL SYNDROME
Authors: Dowhaniuk J K , Chorlton S , Teskey G , Loukov D , Verschoor C , Owens J , Clause R , Pernica J , Bowdish D , Surette M , Ratcliffe E
Published: February 2020

Background

Both intestinal dysbiosis and central-line associated blood stream infections (CLABSI) have been well documented in children with short bowel syndrome (SBS). Gastrointestinal microbiota prime and regulate mucosal immunity, therefore we hypothesize children with SBS may have longstanding increased intestinal permeability which could lead to mucosal inflammation and predispose to bacteremia.

Aims

We sought to investigate intestinal permeability as well as both intestinal and systemic activation of the inflammatory cascade in children with SBS.

Methods

Two cohorts of children with SBS were consented; with Group 1 including children with SBS requiring central venous catheter (CVC) for parenteral nutrition, and Group 2 including children with SBS without CVC. SBS groups were compared to three control groups including age and sex-matched children with CVC for hematologic disease (Group 3), children without a CVC (Group 4) and healthy adult controls (Group 5). To evaluate intestinal permeability, we quantified circulating bacterial products LPS and MDP through the binding of their respective receptors, TLR4 and NOD2. To determine colonic inflammation, fecal calprotectin was quantified from a single stool sample. Cytokine profiles included IFN-γ, IL-Iβ, IL-8, IL-10, IL-17, TNFα were quantified by Multiplex Immunoassay while gene expression of transcription factors FoxP3+, RORγT, TLR2, and TLR4, were determined by RNA extraction and quantitative PCR.

Results

22 children were recruited in the study (Group 1 n=6, Group 2 n=6, Group 3 n=5, Group 4 n=5) as well as 10 adult control samples (Group 5). The median age of Group 1 was 67 months with a residual small intestine of 26.5cm (IQR 24.7–40) while those in Group 2 were 51 months with a residual small intestine of 55cm (IQR 31.2–89). Circulating bacterial products of LPS and MDP were not different between SBS groups and control children. Serum analysis of cytokine TNFα was significant (p<0.005) however multiple comparator analysis did not identify within group differences. Other cytokines did not differ between groups. Fecal calprotectin levels were not elevated however statistically lower in Group 1 (median 12.8mg/kg; IQR 9.3- 34.9) compared to in Group 2 (median 96mg/kg, IQR 71.6–188.2;) p <0.01. Relative quantification of RNA expression of FoxP3+, RORγT, TLR2, and TLR4 did not differ between groups.

Conclusions

Despite concern of compromised intestinal epithelial barrier function in children with SBS, this study did not detect differences in circulating bacterial products compared to control children as an assessment of intestinal permeability nor increased systemic inflammation. Further research is required to investigate intestinal epithelial barrier function over time and the mechanism of bacteremia in children with SBS.

Funding Agencies

CAGRegional Medical Associates of Hamilton
A47 ENTERIC TUFT CELL HYPERPLASIA FOLLOWING INFECTION WITH THE TAPEWORM HYMENOLEPIS DIMINUTA IS AFFECTED BY NEURONAL BUT NOT BACTERIAL FACTORS
Authors: Rajeev S , Defaye M , Shute A J , Wang A , Wang S J , Altier C , McKay D M
Published: February 2020

Background

Tuft cells are a rare chemosensory population of the intestinal epithelium that detect intestinal parasitic nematodes and release IL-25 to mobilize innate lymphoid type 2 cells (ILC2), which then drive a Th2- dominant nematode expulsion response. Immunocompetent mice develop tuft cell hyperplasia in the small intestine during infection with Hymenolepis diminuta, a non-abrasive lumen dwelling small intestinal cestode parasite. Helminth infections are accompanied by alterations in sensory motor functions of the gut as well as the composition of the microbiota. It is poorly understood if tuft cell hyperplasia is regulated by these immunomodulatory influences.

Aims

To test if mice lacking (1) a functional adaptive immune system, (2) TRPV1+ gut-innervating sensory nerves and (3) a microbiome, display enteric tuft cell hyperplasia following infection with H. diminuta.

Methods

RAG-1-/- (male and female) and germ-free mice (n=3–6) were infected with 5 cysticercoids of H. diminuta and age matched non-infected mice served as control groups. Male C57BL/6j mice were treated with resiniferatoxin (RTX) to ablate TRPV1 +sensory neurons before infection. Mid-jejunum cryostat or paraffin embedded sections immunostained against doublecortin-like kinase -1 (DCLK-1) were blindly scored for tuft cell enumeration at 5–14 days post-infection.

Results

Tuft cell hyperplasia (~10-15-fold increase) was observed in the jejunum of wild-type mice at 11 days post infection with H. diminuta, by which time worms are expelled. Infected RAG-1-/- mice develop tuft cell hyperplasia of lesser magnitude than wild-type mice. Germ-free mice displayed tuft cell hyperplasia and kinetics of worm expulsion that were not different from wild-type mice. RTX-treated mice with confirmed loss of TRPV1+ nerve fibers in the gut and their cell soma in the dorsal root and nodose ganglia, had a greater increase (~2-fold) in tuft cell numbers compared to H. diminuta-only mice at 11 days post-infection.

Conclusions

Knowledge of how the host senses helminths in the gut lumen is central to the host-parasite interaction. Using the H. diminuta-mouse model system we find that tuft cell hyperplasia is largely, but not entirely dependent on adaptive immunity, occurs independent of the gut microbiota, and, intriguingly, TRPV1+ sensory nerves appear to act as a brake on the system, limiting the magnitude of the hyperplasia.

Funding Agencies

CIHRNSERC, Henry Koopman’s Memorial scholarship
A49 CO-INFECTION WITH PARASITIC WORMS ENHANCES THE ABILITY OF SALMONELLA TO COLONIZE THE GUT LUMEN AND DEWORMING RESTORES COLONIZATION RESISTANCE TO SALMONELLA
Authors: Brosschot T P , Lawrence K M , Kennedy M H , FitzPatrick R D , Moeller B E , Han J , Borchers C , Reynolds L A
Published: February 2020

Background

Chronic infections with intestinal helminths occur primarily in world regions where infections with bacterial pathogens are also common. Research so far has shown that helminths can promote bacterial infection, however, the precise mechanisms of this are unknown. Current helminth control strategies involve mass deworming programs, and it is as yet unclear how deworming impacts susceptibility to bacterial infections in helminth-affected areas.

Aims

Our aims were to decipher the mechanistic details by which helminths can promote intestinal bacterial infection, and to determine how deworming affects susceptibility to intestinal colonization by bacterial pathogens.

Methods

Using a mouse model of enteric helminth-bacterial coinfection, we examined how the small intestinal helminth Heligmosomoides polygyrus promotes intestinal colonization by Salmonella enterica serovar Typhimurim. To study the effect of deworming of concurrent Salmonella infection, we treated our helminth-infected mice with the anthelmintic drug Strongid P both before and after Salmonella (co-) infection. To examine whether heightened Salmonella colonization during helminth infection depended on the ability of Salmonella to invade host tissue, we compared the ability of wild-type Salmonella or an invasion-deficient mutant (ΔinvA) to colonize during helminth co-infection.

Results

An ongoing helminth infection resulted in high levels of Salmonella in the small intestine after co-infection, however, when mice were dewormed prior to Salmonella co-infection, they were no longer susceptible to high small intestinal Salmonella burdens. In contrast, when helminth-infected mice are dewormed after Salmonella has already co-colonized, high Salmonella burdens persisted in the small intestine. Further, we found that during helminth co-infection, Salmonella primarily expands in the gut lumen rather than in the small intestinal tissue, and in line with this, a Salmonella invasion mutant was able to colonize the intestine to a similar extent to wild-type Salmonella during helminth infection.

Conclusions

Deworming experiments have revealed that the effects of H. polygyrus on promoting Salmonella colonization in the small intestines depend on the ongoing presence of the helminth. Deworming did not revert bacterial burdens once Salmonella had colonized, suggesting that an ongoing helminth infection reduces colonization resistance to Salmonella infection but was not required for Salmonella to persist after initial colonization by Salmonella. Further, we discovered that Salmonella expansion during helminth infection is independent of bacterial invasion of host tissue.

Funding Agencies

CIHR
A56 THE USE OF HIGH VOLUME PLASMAPHARESIS IN ACUTE LIVER FAILURE
Authors: Tam L , Sy E , Karvellas C J
Published: February 2020

Background

Acute liver failure (ALF) can result in irreversible shock, cerebral herniation or development of multiple organ failure (MOF). One randomized study and a separate case series have demonstrated the safety and potential improvement in transplant-free survival with the use of high volume plasmapheresis (HVP). HVP is defined as an exchange of 8-12L or 15% of ideal body weight with fresh frozen plasma. In ALF, cytokines are responsible for the progression of MOF and HVP removes these cytokines from the systemic circulation. We report a case of implementing HVP in an adult with ALF in the intensive care unit (ICU) at a tertiary care center.

Aims

This case and the associated literature review highlight the value of HVP in ALF.

Methods

Case report and literature review.

Results

We report a case of a 34-year-old male who presented in ALF secondary to unknown ingestion. He was admitted to the ICU for worsening transaminitis, coagulopathy, hepatic encephalopathy, renal failure and hemodynamic instability which required vasopressor and ventilatory support. A discussion was made with hepatologists at a regional transplant center for potential consideration of either transplant or Molecular Adsorbent Recirculating System (MARS) therapy. However, the patient was too hemodynamically unstable for transport and also began to develop signs of cerebral edema. As a result, they recommended a trial of high volume plasmapheresis. Shortly after initiation, the patient’s hemodynamic, respiratory, and biochemical parameters began to improve, resulting in less vasopressor and ventilator support (Table 1). Despite improvements in these parameters, the patient’s cerebral edema continued to worsen and an electroencephalogram showed signs of a very low likelihood of functional neurological recovery. Given the overall picture, the patient’s spouse decided to withdraw care.

Conclusions

Presently, liver transplantation remains the only definitive management strategy for ALF patients, but many do not survive to liver transplant or are not candidates for medical or psychosocial reasons such as with this case. As a result, this case demonstrates the potential benefits of conducting HVP in centers without access to MARS or transplantation. However, although HVP did improve certain parameters for this patient, it did not improve overall prognosis. This suggests that prognosis may not improve once a certain threshold of MOF develops. Therefore, in this case and the associated literature review the optimal timing of initiating HVP remains unclear.

Funding Agencies

None
A69 MULTIPLE FUNCTIONAL GASTROINTESTINAL DISORDERS IN JORDANIAN CHILDREN, NATIONWIDE STUDY
Authors: Altamimi E
Published: February 2020

Background

Functional gastrointestinal disorders (FGIDs) are common in children worldwide. Multiple FGIDs might share some etiopathogenesis, which makes finding multiple disorders in a child a possibility.

Aims

Estimate the prevalence of FGIDs in Jordanian children prospectively, whether as a single or combined disorders.

Methods

A prospective, cross-sectional study was conducted in 6 cities in Jordan. Children between the ages of 4–18 were recruited. A validated Arabic language questionnaires based on Rome III criteria were filled by the participants if older than 10 years and by the parents if younger than 10 years.

Results

A total of 1587(79.35%) participants filled the questionnaires. 814 (51.29%) were younger than 10 years. FGIDs was diagnosed in 204 (25.03%) of younger children. In children between (11 and 18), 310 (40%) were diagnosed with FGIDs.

In children (4–10 yrs.) who were diagnosed with FGIDs, 15.5 % had two disorders, while 3% had three or more disorders. The most common combination was aerophobia and functional constipation, comprising 22.58% of combined disorders. In children (11–18 yrs.) with FGIDs, 22.27% had two disorders and 7% had three or more disorders. Interestingly, the most common combination was aerophagia and functional constipation also, representing 34% of the combined cases.

Conclusions

Functional gastrointestinal disorders are common in Jordanian children. Multiple Functional gastrointestinal disorders may coexist. Diagnosis of one disorder should not prevent us from investigating other disorders.

Funding Agencies

None
A72 VARICEAL BLEED & PORTAL HYPERTENSIVE GASTROPATHY IN A NON-CIRRHOTIC PATIENT WITH ISOLATED SPLENOMEGALY
Authors: Hasan S , Dmitriew M , Leonard J
Published: February 2020

Background

Portal hypertension caused by cirrhosis is the most common etiology of esophageal varices. However, abnormalities of the spleno-portal axis in the absence of liver disease may also cause portal hypertension resulting in varices. We report a rare case of esophageal variceal bleed in a non-cirrhotic patient with isolated splenomegaly secondary to chronic G-CSF therapy.

Aims

This report outlines the case of a patient with Cohen Syndrome (CS) who presented with an upper gastrointestinal (GI) bleed in the setting of previously documented splenomegaly and portal hypertension. We expand on the clinical investigations, diagnosis, treatment plan and hospital course of this patient.

Methods

Case report, review of literature.

Results

A 26-year old male with previously diagnosed CS presented with large volume hematemesis and pancytopenia. CS is a rare autosomal recessive disorder. In our patient this manifested with congenital neutropenia, microcephaly, retinal dystrophy and global developmental delay. He required long term G-CSF therapy to manage chronic neutropenia and subsequently developed splenomegaly, a known side effect. The most recent MRI identified stable splenomegaly with a craniocaudal length of 23 cm, normal liver size and no radiographic evidence of cirrhosis. The imaging was also significant for gastroesophageal and splenorenal varices but no ascites or recanalization of the umbilical vein. A recent liver biopsy had shown mild pericellular fibrosis with no active liver disease or cirrhosis. In the past, the patient had declined EGD, therapeutic splenectomy or assessment of hepatic venous pressure gradient through invasive venography. His liver enzymes, bilirubin and albumin had always been within normal limits. The patient had no history of GI bleeding. Previous investigations for hematologic malignancies or myelodysplastic syndrome had been negative. Upon admission, an urgent EGD revealed active variceal bleeding in the esophagus and portal gastropathy. Given the extent of his congenital orofacial abnormalities a variceal band ligator could not be passed for appropriate intervention. The patient was transferred to the Intensive Care Unit and managed with intravenous proton pump inhibitor, octreotide, as well as transfusions of packed red blood cells, platelets and fresh frozen plasma. Within the next 48 hours, the patient underwent successful transjugular intrahepatic portosystemic shunt and CT-guided coil placements for the bleeding varices.

Conclusions

This is a rare case of variceal bleed in a non-cirrhotic patient with portal hypertension from iatrogenic splenomegaly. While there are previous reports of spontaneous splenic rupture secondary to G-CSF therapy we are the first to report variceal bleed as a complication. This is a life-threatening consequence that requires urgent intervention and intensive care.

Funding Agencies

None
A77 FURTHER CARACTERIZATION OF THE 67 KDA LAMININ RECEPTOR (67LR) IN COLORECTAL CANCER CELLS
Authors: Cloutier G , Khalfaoui T , Beaulieu J
Published: February 2020

Background

The 67 kDa laminin receptor (67LR) was the first non-integrin cell surface receptor for laminin isolated on laminin affinity columns from cancer cells in the 1980’s. Initially, 67LR is found as a cytoplasmic precursor of a 37 kDa protein, named 37LR, associated with the small ribosomal subunit. In human cells, 37LR allows the formation of the polyribosome complex and plays a key role in the initiation of translation. The mechanism by which the ribosomal protein becomes the 67LR membrane receptor is still unclear. It is presumed that the process involves post-translational modifications combined with homo or hetero-dimerization with non-associated ribosomal proteins. It has been shown that 37/67LR regulates adhesion and proliferation of normal human intestinal epithelial cells. Interestingly, overexpression of 37/67LR is correlated with aggressiveness and a poor prognosis in a wide variety of cancers.

Aims

The aim of this study was to confirm the overexpression of 37/67LR at the membrane of colorectal cancer cells and to identify its homo or heterodimerization partners.

Methods

To detect the expression of 37/67LR in colorectal cancer we performed an indirect immunofluorescence on tissues from normal and diseased colons. To confirm the presence of 67LR at the membrane of Caco-2 cells we used a cellular fractionation extraction protocol combined with ultracentrifugation and detergent treatment to separate ribosome-containing fractions from the membranes and isolate the membrane associated 67LR. Mass spectrometry analysis to study the molecular identity of 67LR was performed on immunoreactive bands corresponding to 37LR and 67LR.

Results

Immunolocalization of 37/67LR revealed an overexpression in colorectal cancer tissues. Following analysis by western blotting, immunoreactive 67LR protein was found in the soluble fraction after ultracentrifugation at 210,000 x g while 37LR was detected in the insoluble counterpart which was solubilized after treatment with detergent, suggesting that 37LR is associated with the membrane. Mass spectrometry analysis of these fractions indicated that 37LR was not identified in the immunoreactive bands of 67LR in the soluble fraction but identified the 67 kDa elastin binding protein, another 67 kDa cell surface laminin receptor.

Conclusions

These results indicate that 37LR is overexpressed in colorectal adenocarcinoma cells. Further characterization of the receptor by cell fractionation and mass spectrometry indicated that the 67 kDa immunoreactive form is not related to 37LR. Supported by CIHR.

Funding Agencies

CIHR
A101 USTEKINUMAB LEVELS MEASURED DURING INDUCTION ARE ASSOCIATED WITH CLINICAL AND BIOCHEMICAL OUTCOMES AT WEEK 12 OF TREATMENT IN CROHN’S DISEASE
Authors: Walshe M , Borowski K , Boland K , Rho S , Stempak J , Silverberg M
Published: February 2020

Background

Therapeutic drug monitoring (TDM) helps guide use of anti-TNF drugs in IBD patients. In addition, higher anti-TNF levels during induction therapy have been shown to be associated with better clinical and endoscopic outcomes. The role of TDM for more novel biologics such as ustekinumab (an anti- IL-12/23 antibody used to treat Crohn’s disease) remains to be elucidated.

Aims

We set out to investigate correlations between ustekinumab drug levels measured during induction with clinical and biochemical outcomes in patients with Crohn’s disease.

Methods

Patients with Crohn’s disease commencing treatment with ustekinumab were recruited from a single tertiary referral centre. Standard weight-based induction dosing was used. TDM was performed at week 2 and week 6 following IV induction dose. A drug-tolerant assay (Prometheus) was used. Kruskal-Wallis test was used to examine association between induction dose and ustekinumab levels. CDAI, CRP, and faecal calprotectin (FCP) were measured at week 12. Pearson correlation co-efficient was used to assess the relationship between ustekinumab levels and i)CDAI ii)CRP and iii)FCP at week 12.

Results

A total of 38 ustekinumab levels in 21 patients were measured. Week 2 ustekinumab levels were available for 17 patients, 16 (94.1%) of whom had levels of greater or equal to 25μg/mL. (1 patient had a level of 19.5μg/mL.) Week 6 ustekinumab levels were available for 21 patients; median 15μg/mL (IQR 9.9–21.3). No patients had detectable antibodies to ustekinumab. There was no significant association between absolute induction dose and week 6 ustekinumab levels; p=0.46.

Of the 21 patients with week 6 levels, CDAI, CRP and FCP were available for 18, 18 and 16 patients respectively; Median CDAI 103(IQR 42–249), median CRP 2.3mg/L(IQR 1.0–11.3), median FCP 269μg/g(IQR109-932).

There was a significant negative correlation between week 6 ustekinumab levels and CDAI; r=-.609, p=0.007. A negative correlation between week 6 ustekinumab levels and FCP was also significant; r=-.526, p=0.037. There was no significant correlation between week 6 ustekinumab levels and CRP; r=-.259, p=0.298.

Conclusions

We have demonstrated inter-patient variation in drug pharmacokinetics at week 6 following induction dose of ustekinumab in patients with Crohn’s disease. Drug levels at week 6 are significantly associated with clinical and biochemical markers of disease activity (CDAI, faecal calprotectin) at week 12. Measurement of week 6 ustekinumab levels may aid early identification of patients at risk of primary non-response to ustekinumab.

Funding Agencies

Testing provided by Prometheus