bluuebunny/crossref_metadata_2025 huggingface dataset:
A26 DECONSTRUCTING DISTRESS: STAKEHOLDER ENGAGEMENT FOR EVIDENCE-BASED, PATIENT-CENTERED INTERVENTIONS FOR THE MANAGEMENT OF IBD-ASSOCIATED PSYCHOLOGICAL DISTRESS
Authors: Heisler C , Rohatinsky N , Stewart M , Vallis M , Shepherd T , Wozney L , Cassidy C , Currie B , Phalen-Kelly K , Robar J , Targownik L E , Huard T , Neil E , Jones J
Published: February 2022

Background

The growing prevalence of Inflammatory Bowel Disease (IBD) along with increasing complexity of providing high-quality, patient-centered care within a resource-constrained healthcare environment presents a major challenge. IBD-related psychological distress (IBD-PD) is the emotional impact of IBD and is associated with mental health disorders, increased disease severity, and premature mortality. With estimates of nearly 90% of IBD patients experiencing PD, the inability to provide high-quality, person-centered care for IBD-PD that is proportionate to clinical need is a significant care gap in the Canadian healthcare system.

Aims

To generate stakeholder-derived data to inform the design and development of stepped-intensity, cognitive behavioral therapy-based interventions for IBD-PD using evidence-based, patient–centered interventions and implementation strategies.

Methods

Virtual semi-structured interviews were conducted from September to October 2021. The interview guide was developed iteratively by researchers, IBD care providers, and patient research partners and guided by the COM-B Model of Behaviour and the Theoretical Domains Framework. Questions assessed perceptions, experiences, barriers, and facilitators to accessing IBD-PD care. Adults diagnosed with IBD were recruited from academic centers across Canada. Interviews were co-facilitated by a researcher and patient research partner, audio recorded, and transcribed. Using thematic analysis, codes were generated to identify themes using an inductive approach.

Results

As of October 2021, six interviews have been completed, with data collection ongoing. The mean participant age was 34.3 years (range 21–55 years) with 100% of respondents being female. The majority of participants worked full time (4/6, 67%) and all had completed at least high school. Diagnoses of Crohn’s Disease (3/6, 50%) and ulcerative colitis (3/6, 50%) were evenly distributed. Thematic analyses identified five major themes: 1) Lack of holistic care and acknowledgement of IBD-PD; 2) System-level and financial barriers to psychological support; 3) Lack of psychological support from providers with an understanding of IBD; 4) Preference for individualized virtual-based support; 5) Heavy reliance on informal support structures (caregivers) due to lack of access to formal psychological support.

Conclusions

As part of human-centered design, stakeholder engagement is key to understanding behavioral, social, attitudinal, and environmental barriers and facilitators for accessing IBD-PD care. Interviews are ongoing and specific intervention functions will be defined and incorporated into patient-centered implementation strategies.

Funding Agencies

None
A35 DNA HYPOMETHYLATION INHIBITS TUFT CELL-DERIVED COLITIS-ASSOCIATED CANCER
Authors: Larsen F , Good H J , Shin A E , Zhang L , Asfaha S
Published: February 2022

Background

Colorectal cancer is the second leading cause of cancer death in Canada. A major risk factor for the development of colorectal cancer is chronic inflammation leading to colitis-associated cancer (CAC). We previously described a CAC mouse mode in which tumors arise from DCLK1+ tuft cells following loss of the tumor suppressor adenomatous polyposis coli (APC) and induction of colitis. Interestingly, both colitis and CAC display epigenetic changes that modulate gene expression. Specifically, DNA methylation is altered in colitis, but its role in colonic tumorigenesis is not known. We hypothesize that inhibition of DNA methylation in DCLK1+ tuft cells reduces colonic tumorigenesis.

Aims

In this study, we aim to investigate the role of DNA methylation in CAC by inhibiting DNA methylation by genetic and pharmacologic means.

Methods

We crossed our Dclk1-CreERT2/Apcf/f mice to DNMT1f/f mice to delete the DNA methyltransferase DNMT1 in DCLK1+ tuft cells. We induced CAC in Dclk1/Apcf/f and Dclk1/Apcf/f/DNMT1f/f mice by administering three doses of tamoxifen followed by 2.5% dextran sodium sulfate (DSS) for five days. Fourteen weeks later we assessed colonic tumor number and size. Lineage tracing of Dclk1+ cells was also examined in colonic tissues from all mice. In a separate cohort of Dclk1/Apcf/f mice, we induced colitis and treated the mice with six doses of the DNA de-methylating drug 5-AZA-2’-deoxycytidine (5-AZA) or vehicle. Ki67 immunostaining was additionally performed to assess cellular proliferation in the colon.

Results

Deletion of DNMT1 in DCLK1+ cells significantly inhibited the number and size of colonic tumors. Treatment of mice with 5-AZA similarly reduced the overall number of mice with tumors, as well as, the number and size of tumors per mouse. Interestingly, 5-AZA treatment was associated with reduced colonic proliferation as assessed by fewer Ki67+ cells, and quiescent DCLK1+ cells that did not lineage trace. Furthermore, deletion of DNMT1 or treatment with 5-AZA reduced the number of lineage tracing events detected upon exposure to low DSS.

Conclusions

Our findings demonstrate that loss of Dnmt1 or 5-AZA treatment reduces CAC formation. Furthermore, 5-AZA appears to exert its anti-tumor effects by reducing proliferation and preventing tuft cell stemness. Our data demonstrates that altering DNA methylation plays an important role in CAC.

Funding Agencies

CIHR
A46 BIOGEOGRAPHIC VARIATION AND FUNCTIONAL PATHWAYS OF THE GUT MICROBIOTA IN CELIAC DISEASE
Authors: Libertucci J , Constante M , Galipeau H J , Szamosi J C , Rueda G H , Pinto-Sanchez M I , Southward C M , Rossi L M , Fontes M E , Chirdo F G , Surette M , Bercik P , CAMINERO FERNANDEZ A , Verdu E
Published: February 2022

Background

Genes and gluten are necessary, but insufficient to cause celiac disease (CeD), as risk alleles (DQ2 or DQ8) are prevalent in ~30–40% of the healthy population consuming gluten. Gut microbiota shifts and infections have been proposed as risk modulators. Biogeographic characterization of the microbiota in CeD patients and its functional significance are limited, particularly at the duodenum, the main site of inflammation.

Aims

We studied microbiota composition and predicted function along the gastrointestinal tract and investigated the impact of host genetics and CeD activity.

Methods

We used 16S rRNA gene sequencing (Illumina) and predicted gene function analysis (PICRUSt2), to study the microbiota in duodenal biopsies (D1, D2 and D3), duodenal aspirates, and fecal samples from patients with active CeD (n= 24) (biopsy and serology confirmed) and controls (non-celiac, n= 41). CeD alleles were determined in consented participants using DQ-CD typing. Small intestinal samples from controls (DQ2-/- = 14; DQ2+/- = 7) and CeD (DQ2+/- = 12) were used for further analysis and to colonize C57BL/6 germ-free mice for gluten metabolism studies.

Results

Microbiota community composition and predicted function was mainly determined by intestinal location (P= 0.001). Within the duodenum, but not in stool, CeD patients had increased abundance of opportunistic pathogens. Escherichia coli was increased in D1, Streptococcus pneumoniae in D2, and Neisseria in D3 versus controls. Predicted bacterial protease and peptidase genes were altered in CeD DQ2+/- patients versus DQ2-/- controls. In DQ2+/- controls, fewer predicted bacterial genes were altered compared to CeD DQ2+/- patients. Impaired capacity to metabolize gluten was confirmed in germ-free mice colonized with microbiota from CeD (DQ2+/-), but not DQ2+/- or DQ2-/- controls.

Conclusions

In the duodenum, CeD is associated with increased opportunistic pathogens and altered bacterial proteolytic profile. These are not determined by genetic predisposition, as CeD and controls with similar genetic background differed in its predicted bacterial proteolytic function, which was confirmed in mice colonized with duodenal microbiota using these cohorts. Our study highlights the need for defining sampling location in studies investigating the role of microbiota in CeD.

Funding Agencies

CAG, CCC, CIHR
A56 TUFT CELL RESPONSES DURING ACUTE- AND LATE-STAGE GIARDIA INFECTION
Authors: Sosnowski O , Allain T , Fekete E , Mckay D M , Buret A
Published: February 2022

Background

Epithelial tuft cells can detect and respond to enteric infections and appear to help clear some intestinal parasites. Through tuft cell luminal surface receptors, tuft cells can sense ligands directly supplied by a parasite, or indirectly via excretory/secretory products. We hypothesize that microbiome alterations may also modulate tuft cell-derived gut responses. Tuft cells release the alarmin cytokine IL-25 which, upon acting on type 2 innate lymphoid cells (ILC2), ultimately lead to tuft and goblet cell hyperplasia. Upon helminth infections, tuft and goblet cell hyperplasia occurred concurrently, and coincided with the peak of infection. The role of tuft cells in infections with the enteric protozoan parasite Giardia sp. is unknown. The aim of our study is to characterize how tuft cells may be implicated in the pathophysiology of giardiasis, in an attempt to uncover novel regulatory pathways of intestinal physiology.

Aims

In this study, we aim to characterise the tuft cell response to Giardia infection during acute and late stages of infection and to assess goblet cell hyperplasia.

Methods

5–7-week-old C57BL/6 mice and tuft cell-deficient mice ( Pou2f3-/-) were orally gavaged with 5x104Giardia muris trophozoites and scarified at days 4, 11 and 21 post-infection. Parasite burden was assessed in the duodenum. Immunofluorescence (IF) staining of doublecortin-like kinase 1 (DCLK1) – a marker of tuft cells – was performed on C57BL/6 mice jejunum tissue sections and the number of tuft cells was quantified. Goblet cells were quantified in PAS/AB-stained jejunum sections. Quantitative PCR (qPCR) was performed on Dclk1, the epithelial secretory cell transcription factor Atoh1, and the mucus gene Muc2.

Results

G. muris infected C57BL/6 mice displayed high parasite load at days 4 ( p<0.05) and 11 ( p<0.05), with no or low parasite burden at day 21 ( p<0.05). Pou2f3-/- mice showed less robust parasite burden at days 4 and 11, and similar low parasite burden at day 21, compared to WT mice. At day 21, tuft cell (DCLK1+) counts ( p<0.05) and Dclk1 mRNA expression levels were increased in Giardia infected mice in the jejunum. Goblet cell number and Atoh1 and Muc2 expression were increased at day 4 post-infection.

Conclusions

The data demonstrate that tuft cells expand late in Giardia infection, suggesting that upon parasite infection, tuft cells may possess roles in tissue repair or clearance of infection. Tuft cell-deficient mice ( Pou2f3-/-) had lower parasite burden early in Giardia infection, counter-intuitively suggesting that tuft cells may facilitate trophozoite colonization, further highlighting the novelty of these findings. The crosstalk between tuft cells, Giardia, and other host responses during acute and late stages of infection remain to be fully characterised.

Funding Agencies

NSERC
A69 LONG-TERM EFFECTS OF TORKELSON SYNDROME
Authors: Dinn S E , Wrobel I , Bhandal S , Brundler M
Published: February 2022

Background

Torkelson Syndrome is a rare, familial enteropathy with villous edema causing recurrent episodes of life threatening vomiting and secretory diarrhea in childhood, with children being well between episodes. The only description, of a Mennonite family from southern Alberta, suggests normal growth and no long term sequelae. Severe laboratory abnormalities common during bouts of diarrhea (hypoalbuminemia, neutropenia and electrolyte abnormalities) normalize in the asymptomatic phase except for decreased IgG subclasses. Typical findings from the duodenum and jejunum do not vary between acute episodes and when well. The pathophysiology is poorly understood, with acute episodes thought to be triggered by a non-specific infection in the setting of IgG2 deficiency.

Apolipoprotein A-IV (APOA4) mutation has been documented in Torkelson syndrome. APOA4 is exclusively expressed in proximal small intestine villous enterocytes. It is thought to be involved in regulating pathways that control inflammation in enterocytes, resulting in decreased inflammation. It may prevent recruitment of leukocytes to inflamed intestinal enterocytes by suppressing P-selectin in the endothelial cells. Fully functioning APOA4 decreases secretion of IL-4 and TNF-a. In theory, abnormalities in APOA4, could result in a robust, unopposed inflammatory response in the small intestine.

Aims

Report possible long-term sequelae of Torkelson Syndrome.

Methods

Case report.

Results

13 year old male with Torkelson syndrome presents with short stature and iron deficiency anemia responsive to oral iron. His weight is at the 0.1%ile, height at the 0.4%ile and BMI at the 1.6%ile.

Life time hypoalbuminemia (20g/L) indicates chronic protein-losing enteropathy. Vitamin D is chronically low but responds to oral supplementation. IgA and IgM are normal, but IgG and its subclasses are decreased. Liver enzymes and electrolytes, including calcium and phosphate, outside of episodes of diarrhea are normal.

Endoscopy shows prominent, thick villi, with fern-like appearance in the duodenum with normal stomach, esophagus, terminal ileum and colon. Biopsy results are consistent with previously described features of Torkelson syndrome with no additional abnormalities. MRE shows mild dilatation of the jejunum with hypertrophic conniventes with fat content. Abdominal ultrasound shows hepatomegaly with coarse echotexture and normal elastography. He has delayed bone age and low bone density.

Conclusions

Patients with Torkelson syndrome, despite their recurrent episodes of life threatening vomiting and secretory diarrhea in childhood, were thought to have no long term sequelae including normal growth.

Our patient, presents with chronic iron deficiency anemia, short stature, delayed bone age and density, and hepatomegaly of unknown significance. This case may broaden our knowledge of this poorly described condition to inform long term management of these patients.

Funding Agencies

None
A93 USEFULNESS OF A NOVEL SMARTPHONE APP IN GASTROINTESTINAL ENDOSCOPY TO TRACK PROCEDURE NUMBERS AND THERAPEUTIC INTERVENTIONS
Authors: Yang D Y , Krahn T , Wang C , Decanini-Trevino J , Wasilenko S , Kroeker K , Davila-Cervantes A , Baugmart D C , Montano-Loza A J , Halloran B , Zepeda-Gomez S
Published: February 2022

Background

Endoscopy teaching is an integral part of gastroenterology (GI) training. Though the number of completed endoscopic procedures does not equate competency, procedure tracking is useful for monitoring an individual’s learning progress. Currently, procedure tracking is typically done on an informal basis using paper or electronic spreadsheets. These methods are non-standardized and may not be shareable between trainees and their programs.

Endostation is a smartphone app created by the University of Alberta Therapeutic Endoscopy Program to facilitate the tracking of endoscopic procedures. The app allows trainees to record the number of endoscopies and details such as cecal intubation (CI), ERCP cannulation, and therapeutic interventions. Data can be accessed by users via the app and website (www.endostation.ca), allowing for close monitoring of trainees’ learning progress.

Aims

Our primary objective was to evaluate the usefulness of the app for tracking the number of endoscopic procedures and therapeutic interventions. Our secondary objective was to evaluate the acquisition of endoscopy skills based on quality endoscopic parameters such as CI rate and ERCP cannulation rate.

Methods

One therapeutic endoscopy fellow and two GI residents were recruited for the study. Participants were asked to document their procedures over the study period (9-month for therapeutic endoscopy fellow, 12-month for GI residents). Total number of procedures was summed for each trainee. Acquisition of endoscopy skills was tracked by comparing success rates of CI and ERCP cannulation at different points within the study period.

Results

The therapeutic endoscopy fellow recorded 415 cannulation attempts, 209 sphincterotomies, 282 stone extractions, 71 plastic stent placements, and 37 metal stent placements. There was a significant difference in the cannulation success rate when comparing the 1st trimester and the 3rd trimester of the study period (68% vs 85%; p= 0.0012) (Fig 1).

The two GI residents respectively recorded 335 and 170 colonoscopies plus 454 and 305 gastroscopies. Resident 1 recorded 58 polypectomies, 9 esophageal variceal banding, and 16 non-variceal hemostasis. Resident 2 recorded 17 polypectomies, 12 esophageal variceal banding, and 9 non-variceal hemostasis. The CI success rate was significantly higher for both residents when comparing the first 4 months of training vs the last 4 months [24% vs 88% for resident 1 (p=0.00001); 15% vs 42% for resident 2 (p= 0.001)] (Fig 1).

Conclusions

The smartphone app (Endostation) was a useful tool for endoscopic procedure tracking. Data from the app was useful in demonstrating improvement in CI rate and ERCP cannulation rate over the study period.

Funding Agencies

None
A120 AUTOMATED BOWEL PREPARATION DETECTION WITH DEEP. CONVOLUTIONAL NEURAL NETWORKS
Authors: Low D J , Hong Z , Mukherjee A , Jugnundan S , Grover S
Published: February 2022

Background

Introduction: Bowel preparation inadequacy has been shown to increase post-colonoscopy colorectal cancer. As such, the USMSTF recommends repeating colonoscopy within 1 year if bowel preparation is inadequate. However, bowel preparation documentation is variable in clinical practice, and physician recommendations adherent to USMTF guidelines are inconsistent.

Aims

Aims: We present an automated computer assisted method using deep convolutional neural networks to detect bowel preparation and adequacy of bowel preparation with the Boston Bowel Preparation Scale (BBPS).

Methods

Methods: We extracted 38523 images of colonic lumen between 2015 and 2017 from screening colonoscopies. Bowel preparation scores were assessed with BBPS. Adequate bowel preparation was defined as BBPS ≥2, and inadequate bowel preparation was defined as BBPS <2. The dataset was split into 26966 images for training, 7704 for validation, and 3853 for testing. Training data was sampled with replacement from a multinomial distribution to balance subclass distributions in each batch. We developed 2 convoluted neural networks (CNN) using PyTorch with a Densenet-169 backbone pre-trained on ImageNet and fine-tuned on our data for classifying adequacy of bowel preparation (binary) and for subclassification of BBPS (multi-class). We used Adam optimiser with an initial learning rate of 3x10-4 and a scheduler to decay the learning rate of each parameter group by 0.1 every 7 epochs along with focal loss as our criterion for both classifiers.

Results

Results: The overall accuracy on the test data set for BBPS subclassification was 0.91. The sensitivity for BBPS 0, 1, 2 and 3 were 0.84, 0.91, 0.86, and 0.96, respectively. The specificity for BBPS 0, 1, 2, and 3 were 1.00, 0.98, 0.95, and 0.93, respectively. The overall accuracy of the test data set for adequacy of bowel preparation was 0.97. The sensitivity for adequacy of bowel preparation for BBPS <2 and BBPS ≥2 was 0.92 and 0.99, respectively. The specificity for adequacy of bowel preparation for BBPS <2 and BBPS ≥2 was 0.99 and 0.92, respectively.

Conclusions

Conclusion: We present an automated computer-assisted detection method of bowel preparation with deep convolutional neural networks. The algorithm is capable of accurate classification of adequacy of bowel preparation (97%) and subclassification of bowel preparation (91%) with high sensitivity and specificity. This algorithm can be applied to automate documentation of bowel preparation and adequacy of bowel preparation. Additional studies will need to be conducted to demonstrate its applicability in real-time colonoscopy.

Funding Agencies

None
A206 GALLSTONE IMPACTION IN THE DESCENDING COLON WITH SUCCESSFUL ENDOSCOPIC REMOVAL
Authors: Malik G , Yang D Y , Wong K
Published: February 2022

Background

Gallstone impaction in the colon is a rare complication of cholelithiasis, typically because of gallstones migrating into the colon via a cholecystocolonic fistula. Gastrointestinal obstruction from gallstones only develops in 0.3–0.5% of patients with cholelithiasis and accounts for 0.095% of all mechanical bowel obstruction. Successful treatment has been described with endoscopic and surgical techniques.

Aims

This report aims to present a case of colonic obstruction from gallstone that was successfully treated endoscopically.

Methods

We conducted a retrospective chart review on one patient including assessing the history of presenting illness along with biochemical, radiographic, and endoscopic results. We then conducted a narrative literature review on this subject matter.

Results

An 85-year-old male with known cholelithiasis complicated by prior cholecystitis presented with a 2-day history of generalized abdominal pain. Computed tomography (CT) showed fistulisation between the gallbladder and hepatic flexure. Follow-up CT with rectal contrast showed lack of contrast beyond an impacted gallstone in the descending colon (Figure 1A, 1B). The patient was deemed a poor surgical candidate thus endoscopic gallstone extraction was attempted. With a pediatric colonoscope, the 41mm x 51mm gallstone was visualized 70cm from anal verge (1C). The stone was too large to be extracted en-block with snare or basket. Attempts to cut the stone at its surface with a polypectomy snare and other tools were unsuccessful because of the roundness and smoothness of the stone. Although we could chip away at the surface, we were unable to break the seal of the stone against the colon mucosa. We found the most effective method was tunneling through the stone’s centre using a closed rat-tooth forceps, then angling the tip of the scope and pulling the scope back to break off fragments from within. A polypectomy snare was used to further breakup larger fragments to prevent repeat impaction (1D). There was underlying diverticular disease and mild ischemic changes to the mucosa but no stricture. The patient did well post-procedure and was able to tolerate oral intake, pass flatus, and pass bowel movements. He was discharged 3 days later.

A recent systematic review found a total of 38 cases of gallstone obstruction of the colon. Majority of patients (73.6%) ultimately required surgical intervention. Overall mortality is 13.1%.

Conclusions

Gallstone impaction in the colon is uncommon with successful endoscopic treatment seldomly described. This report describes a rare complication of gallstone disease that was successfully treated with widely available endoscopic tools.

Funding Agencies

None
A228 A FERMENTABLE FIBRE FREE DIET ACCELERATES SPONTANEOUS COLITIS DEVELOPMENT AND ALTERS THE GUT MICROBIOME IN MUC2-/- MICE
Authors: Healey G R , Schick A , Jacobson K , Vallance B
Published: February 2022

Background

A key feature of ulcerative colitis (UC) is a defective colonic mucus layer. As Muc2-/- mice lack intestinal mucus, they’re often used to model UC. In these mice, luminal bacteria translocate from the gut lumen, triggering spontaneous colitis by 12–16 weeks of age. Notably, mucus defects are also seen in wildtype mice fed a fermentable fibre free (FF-free) diet. Aside from thinner mucus, FF-free fed mice show increased susceptibility to bacterial infections and a microbiome shift from fibre-utilizing to mucus-degrading bacteria. Indeed, a recent clinical study found that a microbiome shift towards proteolytic bacteria preceded clinical diagnosis of UC

Aims

To determine whether feeding newly weaned Muc2-/- mice a FF-free versus chow or inulin-enriched diet leads to

- more rapid development of spontaneous colitis

- shifts in the gut microbiota towards protein fermentation

Methods

Newly weaned Muc2-/- mice (3–4 weeks old) were fed 1 of 3 diets: 1) usual chow (Chow; 14.7% fibre mix), 2) FF-free (10% cellulose – poorly fermented) and 3) inulin-enriched (IN; same nutritional content as FF-free, with 10% inulin instead of cellulose). Body weight, diet intake and disease activity were monitored daily. By day 10, mice in the FF-free group developed severe colitis requiring euthanization. At this time, cecal contents (short-chain fatty acid [SCFA] analysis) and colonic tissue from all mice were collected for alcian blue/PAS staining and histopathological scoring. Stool was collected for 16S rRNA sequencing

Results

FF-free fed mice consumed fewer calories (p=0.0073), experienced less body weight gain (p=0.002), had colonic shortening (p<0.0001) and higher disease activity scores (p<0.0001) than mice fed the IN diet. Histopathological scores were higher in FF-free versus Chow (p<0.0001) and IN (p<0.0001) fed mice. Goblet cell mucin staining was reduced in FF-free compared to Chow and IN fed mice. Beta-diversity analysis showed clear differences in microbiome composition between groups. Acetate, product of fibre fermentation, was higher in the Chow (p<0.0001) and IN (p=0.0195) groups whereas branched-chain fatty acids (BCFA), product of protein fermentation, was higher in the FF-free group (p<0.0001)

Conclusions

Spontaneous colitis development in FF-free fed Muc2-/- mice was observed within 10 days (5–6 weeks old) of weaning whereas Chow or IN fed mice showed minimal to no signs of colitis, respectively. A diet devoid of fibre also led to less mucin staining and a gut microbiome shift that favoured BCFA over SCFA production, suggesting the microbiota of FF-free fed Muc2-/- mice are targeting mucosal proteins concurrent with disease exacerbation. These findings support future studies examining whether consumption of low fibre diets in UC patients worsen disease outcomes whereas diets rich in fibre and/or inulin prove beneficial

Funding Agencies

CCC, CIHRMSFHR Trainee Award, CH.I.L.D foundation
A232 TUFT CELLS COORDINATE RAPID EXPULSION OF THE TAPEWORM H. DIMINUTA BUT ARE NOT REQUIRED FOR ENHANCED IMMUNITY AGAINST THE NEMATODE, H. POLYGYRUS, IN MICE PREVIOUSLY INFECTED WITH H. DIMINUTA
Authors: Rajeev S , Leon-Coria A , Wang A , Finney C , Mckay D M
Published: February 2022

Background

The tuft cell is an important sentinel that monitors the gut lumen and coordinates immunity against parasitic nematodes. We showed small intestinal tuft cell hyperplasia 11 days post-infection (dpi.) with the tapeworm Hymenolepis diminuta: a time when the parasite is no longer present in murine hosts. This may be a way by which the host protects itself from subsequent helminth-infections, a common phenomenon in parasite-endemic world regions. We test this supposition using Pou2f3-/- mice that lack tuft cells.

Aims

To test the hypothesis that tuft cells are important in the anti-worm response in H. diminuta ( H.d.)-infected mice subsequently infected with the nematode parasite Heligosomoides polygyrus ( H.p.).

Methods

Male C57BL6 and Pou2f3-/- mice (8–12 weeks) were infected with 5 H.d. cysticercoids ± 200 H.p. larvae at 10 dpi with H. diminuta (non H.p. mice - control). Upon necropsy at 24 dpi H. diminuta (i.e. 14 dpi H.p. in co-infected mice), both worms were ennumerated in small intestinal washings, H.p. granulomas examined and fecal egg counts performed. Small intestinal segments were stained for tuft (DCLK1+) and goblet cells (PAS+). As a surrogate of successful infection, IL-4 and IL-10 were measured in supernatants from concanavalin-A treated splenocytes.

Results

Wild-type (WT) mice expel H. diminuta by 11 dpi and this was delayed in Pou2f3-/-mice, with worms readily detectable at 14 dpi and absent by 21 dpi. Despite the delayed expulsion, both WT and Pou2f3-/- mice showed increased splenic production of IL-4 and IL-10; however, unlike WT mice, H. diminuta-infected Pou2f3-/- mice show no increase in jejunal goblet cell numbers. Mice infected with H. diminuta displayed a degree of increased resistance to H.p.-infection defined by reduced worm and egg burdens, and increased granuloma formation in comparison to H.p.-only infected animals. In this sequential co-infection model, there were no significant differences between WT and Pou2f3-/- mice in the response to H.p.

Conclusions

The absence of tuft cells slows expulsion of H. diminuta from its non-permissive mouse host and correlates with diminished goblet cell hyperplasia. Hypothesizing that H. diminuta-evoked tuft cell hyperplasia would enhance the immune response to a subsequent infection with an unrelated nematode parasite proved incorrect. While H. diminuta-infected mice were partially protected from H.p., response was similar in WT and Pou2f3-/- mice. Thus tuft cells are important in worm detection: yet, our co-infection data suggests that other events initiated by the primary worm infection impact the outcome of subsequent infection with a different helminth and tuft cells have a limited, if any, role to play in this helminth-host-helminth interaction.

Funding Agencies

CIHRNSERC, Eye’s High International doctoral scholarship
A256 SURVEILLANCE OF SMALL, NON-FUNCTIONING, ASYMPTOMATIC PANCREATIC NEUROENDOCRINE TUMORS: THE BRITISH COLUMBIA EXPERIENCE
Authors: Jiang S X , Towfighi S , Owen D , Tomaszewski M , Harris A , Donnellan F
Published: February 2022

Background

Expert consensus surrounding surveillance for small, non-functioning, asymptomatic pancreatic neuroendocrine tumors (PNETs) remains conflicting. Recent observational studies have shown that surveillance is a safe strategy while large database studies show superior overall survival with surgical resection.

Aims

To describe the growth of small (<2cm), non-functioning, asymptomatic PNETs undergoing surveillance at a tertiary hospital in British Columbia.

Methods

We conducted a retrospective case series of patients with biopsy-proven, non-functioning, asymptomatic PNETs which were <2cm by RECIST criteria at diagnosis, who were followed through active surveillance at Vancouver General Hospital, British Columbia from February 1, 2011-February 1, 2021. Patients were included if serial imaging, whether by endoscopic ultrasound or cross-sectional imaging, was available for a minimum of 24 months.

Results

Of the 57 patients with pathology-proven PNETs that were identified, 14 cases were included after excluding those with resection within 1 year (n=17), lost to follow up (n=13), metastatic disease (n=6), size greater than 2cm at diagnosis (n=4), and with concurrent cancer (n=3). Included patients were predominantly female (n=10, 71%), Caucasian (n=8, 57%), and had a mean Charlson comorbidity index of 3.14. Mean PNET size at diagnosis was 12mm with standard deviation of 4.26mm. Tumors were located in the pancreatic head (n=4, 29%), body (n=6, 42%), and tail (n=4, 29%). Of 8 patients who had Ki67 stains, all were <3%, and of 11 patients with mitotic index, all had <2 mitotic figures. As such, of the 8 patients with available WHO grading, all were grade 1. The average follow-up was 49.6 months with an average tumor growth of 0.82mm per year. When grouping these tumors by growth, 9 (62%) tumors exhibited no growth, 2 tumors grew <1mm per year, 2 tumors grew 1-1.5mm per year, and 1 tumor grew 7.7mm per year. Two cases (14%) of PNETs underwent surgical resection due to size surpassing 2 cm. No patients undergoing surveillance developed metastatic disease.

Conclusions

To our knowledge, we have performed the first Canadian series of small, low-grade PNETS and demonstrated that active surveillance is a safe strategy with most tumors exhibiting no growth of several years. Of the subset of PNETs which demonstrate progression, the preceding surveillance strategy did not disadvantage patients in terms of progression to metastases and allowed for delay of potentially morbid surgery. Further research with prospective studies and larger samples should be conducted.

Funding Agencies

CAG
Ability of Infrascanner 2000 to predict post-traumatic cranial hemorrhage volume in low-resource settings: a protocol for a multi-center prospective, observational study
Authors: Fernandez Laura L , Griswold Dylan P , Aristizabal Sarita , Sanchez Diana M , Rubiano Andres M
Published: February 2022

Low- and middle-income countries experience three times more traumatic brain injury (TBI) cases when compared with their high-income country counterparts. The quality of care patients receive in the prehospital setting and emergency department settings are highly variable and often dependent on computed tomography (CT) availability. The implementation of a handheld device that is able to reliably diagnose intracranial hemorrhage (ICrH) in TBI patients is needed in these settings where CT is unavailable. The Infrascanner has shown promise to detect intracranial bleeds in patients with moderate TBI. We aim to determine the correlation between the coefficient provided by the Infrascanner compared to the post-traumatic supratentorial hemorrhagic collections volume in patients with surgical indication in differente trauma centers. This is a multi-center prospective observational study that will be carried out in three trauma centers in Colombia, Guatemala and Pakistan. We calculated a sample size of eighty-six patients with mild, moderate or severe TBI ≥ 15 years old who have a supratentorial hemorrhage abnormality that requires neurosurgical intervention. The Infrascanner’s ability to detect IChR in patients with surgical indications associated to hemorrhage volume when compared with CT is the primary outcome measure. Secondary outcome measure is the correlation of the mean of the six Infrascanner measurement values compared with volume of ICrH as measured from the six manual head CT segmentation measurements. ICrH volume correlation and agreement will be evaluated by the Pearson coefficient and Bland-Altman analysis, and a linear regression analysis will be performed in order to predict IChR from the Infrascanner measurement.
Electrochemotherapy vs radiotherapy in the treatment of primary cutaneous malignancies or cutaneous metastases from primary solid organ malignancies: a protocol for a systematic review and meta-analysis
Authors: McMillan Angus , McElroy Luke , O’Toole Lorcan , Matteucci Paolo , Totty Joshua P
Published: February 2022

Electrochemotherapy has emerged as a valuable tool in the treatment of cutaneous malignancies that are unamenable to surgical resection. Despite growing recognition and recommendation in national guidelines, to date, no Level 1 evidence exists comparing its use to radiotherapy in the management of cutaneous malignancies. A systematic review and meta-analysis will be undertaken in line with the Cochrane Handbook and Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and checklist. A comprehensive search strategy will be applied to MEDLINE, Embase, CINAHL, CENTRAL and ClinicalTrials.gov from the time period from inception to December 2021. Supplementary searches of the grey literature will also be undertaken. Studies in humans which compare treatment with electrochemotherapy to radiotherapy and report tumour response with at least a 4-week follow-up will be eligible. Studies will be included regardless of publication language or country of origin. Screening of studies and data extraction will be undertaken independently by two authors. Our primary outcome will be tumour volume response according to Response Evaluation Criteria in Solid Tumors. We will also extract any secondary outcomes reported, such as patient-reported outcome measures, pain, toxicity/adverse events and progression-free survival. Included studies will be assessed for risk of bias using recognized tools. Evidence quality will be appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. If studies are of acceptable clinical homogeneity and suitable data is extracted, a meta-analysis will be performed. If adequate data are present, various subgroup analyses will be performed. Publication bias will be assessed using a funnel plot and Egger’s test.

PROSPERO CRD42021285415
The Cataphoric Pronoun in Biblical Hebrew
Authors: Garr W Randall
Published: February 2022

The cataphoric pronominal construction has long been recognized in Biblical Hebrew. It is formally redundant, consisting usually of a bound third-person object pronoun and subsequent, coreferential noun or noun phrase. A standard, familiar example is ‘she saw him, the child’ in Exod. 2:6. The following article attempts a comprehensive account of this grammatical construction, including its semantic value, its discourse role, and especially its pragmatic functions in a number of contexts. This article also compares its appearance in the Septuagint, the Samaritan Pentateuch, the Dead Sea scrolls and the Masoretic text. It concludes that, while the cataphoric pronominal construction was a genuine (i.e. non-borrowed) feature of Biblical Hebrew, it was most favoured by the Masoretic tradition in the later Biblical books even though the construction was never grammaticalized.
Long-term effectiveness of a primary care practice facilitation program for chronic kidney disease management: an extended follow-up of a cluster-randomized FROM-J study
Authors: Imasawa Toshiyuki , Saito Chie , Kai Hirayasu , Iseki Kunitoshi , Kazama Junichiro James , Shibagaki Yugo , Sugiyama Hitoshi , Nagata Daisuke , Narita Ichiei , Nishino Tomoya , Hasegawa Hajime , Honda Hirokazu , Maruyama Shoichi , Miyazaki Mariko , Mukoyama Masashi , Yasuda Hideo , Wada Takashi , Ishikawa Yuichi , Tsunoda Ryoya , Nagai Kei , Okubo Reiko , Kondo Masahide , Hoshino Junichi , Yamagata Kunihiro
Published: February 2022

Background

Practice facilitation program by multidisciplinary care for primary care physicians (PCPs) is expected to improve chronic kidney disease (CKD) outcomes, but there is no clear evidence of its long-term effectiveness. We have previously performed a cluster-randomized controlled trial for 3.5 years (the Frontier of Renal Outcome Modifications in Japan (FROM-J) study) with two arms—group A without the program and group B with the program. We aimed to assess the long-term effectiveness of the practice facilitation program on CKD outcomes via an extended 10-year follow-up of the FROM-J study.

Methods

We enrolled patients who were in the FROM-J study. The primary composite endpoint comprised cardiovascular disease (CVD), renal replacement therapy initiation and a 50% decrease in the estimated glomerular filtration rate (eGFR). The secondary endpoints were survival rate, eGFR decline rate and collaboration rate between PCPs and nephrologists.

Results

The occurrence of the primary composite endpoint tended to be lower in group B (group A: 27.1% versus group B: 22.1%, P = 0.051). Furthermore, CVD incidence was remarkably lower in group B (group A: 10.5% versus group B: 6.4%, P = 0.001). Although both mortality and the rate of eGFR decline were identical between both groups, the eGFR decline rate was significantly better in group B than in group A only in patients with stage G3a at enrollment (group A: 2.35 ± 3.87 mL/min/1.73 m2/year versus group B: 1.68 ± 2.98 mL/min/1.73 m2/year, P = 0.02). The collaboration rate was higher in group B.

Conclusions

The CKD practice facilitation program for PCPs reliably decreases CVD events and may reduce the progression of cases to end-stage kidney disease.
The complexity of police decisions: A collaborative study on police decision-making in Belgium
Authors: Feys Yinthe , Van Thienen Bart , Van den Bulck Stijn , Van Poucke Koen , Torreele Rienert , Van Damme Anjuli , De Sterck Maria , Michiels Sylvie , Muyshondt Peter , Verhage Antoinette
Published: February 2022

Street-level police officers are regularly confronted with complex situations and often have to make split-second decisions. Despite the importance of these decisions for procedural justice and police legitimacy, we know little about the factors that impact Belgian police officers’ decision-making. This article explores this topic by means of semi-structured interviews (n = 46) in the Belgian local police. We conclude that there is a variety of factors that play a role. These factors can be divided into four groups: characteristics of the police officer, characteristics of the civilian, organizational characteristics, and situational characteristics. The most influential factors are police officers’ professional experience, laws and regulations, police officers’ personality, one’s colleagues and supervisors, and whether or not the civilian is aggressive and known by the police.
The Use of Force in Higher Education Policing: Implications for Policy and Practice
Authors: Hipple Natalie Kroovand , Hunter Benjamin D
Published: February 2022

The public call for transparency around police use-of-force incidents and incident data must be answered. Campus police departments are no exception. Yet while the fundamentals of policing are universal, campus policing poses unique challenges for officers, and there is little empirical research informing campus policing policy and practice. In this article, we analyse use-of-force incident records and police officer focus group data involving the Indiana University Police Department over a 3-year period. The data reveal that use-of-force incidents most commonly occurred off-campus; most subjects were males not affiliated with the university; and alcohol was usually a factor. Subject resistance actions and officer use of force are discussed. The article concludes with examples of real-world policy applications, presenting an opportunity for urban police departments to look to campus policing as a model of transparency around use-of-force incidents.
A Theory of Participation in OTC and Centralized Markets
Authors: Dugast Jérôme , Üslü Semih , Weill Pierre-Olivier
Published: February 2022

Should regulators encourage the migration of trade from over-the-counter (OTC) to centralized markets? To address this question, we study a model in which banks make costly decisions to participate in an OTC market, a centralized market, or both markets at the same time. Banks differ in their ability to take large positions, what we call their trading capacity. In equilibrium, intermediate-capacity banks find it optimal to participate in the centralized market. In contrast, low- and high-capacity banks find it optimal to participate in the OTC market, due to an endogenous complementarity. Namely, low-capacity banks receive worse terms of trade than in the centralized market but better risk sharing, thanks to the intermediation services offered by high-capacity banks. High-capacity banks receive worse risk sharing than in the centralized market, but profit from the provision of intermediation services to low-capacity banks. While the social optimum has qualitatively similar participation patterns, it prescribes that more customers migrate to the centralized market, and that more dealers enter the OTC market.
Psychosis and the Risk of Stranger Homicides
Authors: Ojansuu Ilkka , Lähteenvuo Markku , Tiihonen Jari , Lehti Martti , Putkonen Hanna
Published: February 2022

Introduction

Psychosis increases the risk of committing homicide, but it remains unclear whether it also affects victim selection. Individual cases of stranger homicide elicit a lot of public attention and outrage, even though evidence of their incidence is scarce.

Methods

Forensic psychiatric reports of 389 patients who had committed homicide in Finland during 1980–2014 were examined to determine the relationship between the offender and the victim. The stranger homicide incidence derived from perpetrators with psychosis was compared to a comparative incidence derived from a group of perpetrators without psychosis (other mental disorders were not excluded) over the time frame 2003–2014. Stranger homicide incidence rates were calculated using Finnish population averages of the study years, assuming a Poisson distribution and reported as per 100 000 person-years among potential victims in the Finnish general population.

Results

Three hundred and eighty nine patients with psychosis had committed 414 homicides, with 40 complete stranger victims and 15 victims known for less than 24 h. Complete stranger homicide incidence committed by individuals with psychosis was 0.022 per 100 000 person-years and 0.13 for individuals without psychosis. When also including victims known for < 24 h, the incidence was 0.031 for individuals with psychosis and 0.28 for individuals without psychosis per 100 000 person-years.

Discussion

Nine out of ten stranger homicides are committed by individuals without psychosis. However, on the basis of a 3.1% prevalence of psychotic disorders in Finland, individuals with psychosis have about a 3- to 5-fold risk of committing stranger homicides as compared to individuals without psychosis.
The “Dream Changer”: a randomized controlled trial evaluating the efficacy of a parent-based intervention for childhood nightmares
Authors: Bourboulis Stephanie , Gradisar Michael , Kahn Michal
Published: February 2022

Study Objectives

Recurrent nightmares in childhood may have a range of detrimental effects for both the child and parents. This randomized controlled trial evaluated the efficacy of a novel parent-based intervention for childhood nightmares, using a new device called the “Dream Changer.”

Methods

A total of 56 children aged 3–10 years (M = 7.1 ± 2.1 years; 51.8% boys), and one of their parents were randomized to either the intervention or waitlist control group. The intervention group received a “Dream Changer”—a light-emitting remote-control-like device that the child was encouraged to take to bed and use upon experiencing a nightmare. Parents completed online surveys at baseline, 1-week, and 2-weeks following the intervention. Parents in the intervention group additionally completed a 3-month follow-up survey. Outcome variables included children’s nightmare frequency, sleep-wake patterns, and sleep anxiety, as well as parents’ daytime sleepiness.

Results

Significant group-by-time interaction effects were found for nightmare frequency (p = 0.001) and sleep anxiety (p = 0.006). Parents of children who received the “Dream Changer” reported fewer nightmares (Mdifference = 1.7, p < 0.001, d = 1.06) and decreased anxiety (Mdifference = 0.9, p = 0.001, d =0.41) at post-intervention, whereas such benefits were not found in the waitlist control group. Three-month follow-up assessments demonstrated that gains were maintained over-time. Interaction effects were not significant for children’s sleep metrics or for parents’ daytime sleepiness.

Conclusions

The present study provides preliminary evidence for the efficacy of a brief, highly accessible intervention for reducing children’s nightmares and nighttime anxiety. Future research may wish to test these effects using larger samples and longer follow-up assessments.

Clinical Trial Registration

The trial has been registered at the Australian New Zealand Clinical Trials Registry (https://www.anzctr.org.au/; Identifier:ACTRN12620000633987).
Modern Family: trusts in a time of rapid social change
Authors: Atkinson Simon , Steadman Joseph
Published: February 2022

This article considers some of the issues arising from the evolution of social and legal understandings of what constitutes “family” in the modern era and the impact of that evolution on older settlements. The article considers the common law’s default conception of familial relationships—who was a settlor’s spouse or child for example—and how that default conception could have been displaced by a settlor or testator. The article then considers some of the legislative interventions of the 20th and 21st centuries and the impact of human rights legislation which have altered the common law’s traditional understanding of family relationship. The article reviews several important cases, including the recent decision of Goodrich v AB [2022] EWHC 81 (Ch), which have considered the impact of these interventions on older settlements. Finally, the article considers some practical tips for settlors, trustees and beneficiaries.