The 2023 Impact of Inflammatory Bowel Disease in Canada: Cancer and IBD.

Cancer is a major cause of morbidity and mortality among people with inflammatory bowel disease (IBD). Intestinal cancers may arise as a complication of IBD itself, while extra-intestinal cancers may arise due to some of the immunosuppressive therapies used to treat IBD. Colorectal cancer (CRC) and small bowel cancer risks remain elevated among persons with IBD as compared to age-and sex-matched members of the general population, and the lifetime risk of these cancers is strongly correlated to cumulative intestinal inflammatory burden. However, the cumulative risk of cancer, even among those with IBD is still low. Some studies suggest that IBD-CRC incidence has declined over the years, possibly owing to improved treatment standards and improved detection and management of early neoplastic lesions. Across studies of extra-intestinal cancers, there are generally higher incidences of melanoma, hepatobiliary cancer, and lung cancer and no higher incidences of breast cancer or prostate cancer, with equivocal risk of cervical cancer, among persons with IBD. While the relative risks of some extra-intestinal cancers are increased with treatment, the absolute risks of these cancers remain low and the decision to forego treatment in light of these risks should be carefully weighed against the increased risks of intestinal cancers and other disease-related complications with undertreated inflammatory disease. Quality improvement efforts should focus on optimized surveillance of cancers for which surveillance strategies exist (colorectal cancer, hepatobiliary cancer, cervical cancers, and skin cancers) and the development of cost-effective surveillance strategies for less common cancers associated with IBD.

The 2023 Impact of Inflammatory Bowel Disease in Canada: Treatment Landscape.

The therapeutic landscape for inflammatory bowel disease (IBD) has changed considerably over the past two decades, owing to the development and widespread penetration of targeted therapies, including biologics and small molecules. While some conventional treatments continue to have an important role in the management of IBD, treatment of IBD is increasingly moving towards targeted therapies given their greater efficacy and safety in comparison to conventional agents. Early introduction of these therapies-particularly in persons with Crohn's disease-combining targeted therapies with traditional anti-metabolite immunomodulators and targeting objective markers of disease activity (in addition to symptoms), have been shown to improve health outcomes and will be increasingly adopted over time. The substantially increased costs associated with targeted therapies has led to a ballooning of healthcare expenditure to treat IBD over the past 15 years. The introduction of less expensive biosimilar anti-tumour necrosis factor therapies may bend this cost curve downwards, potentially allowing for more widespread access to these medications. Newer therapies targeting different inflammatory pathways and complementary and alternative therapies (including novel diets) will continue to shape the IBD treatment landscape. More precise use of a growing number of targeted therapies in the right individuals at the right time will help minimize the development of expensive and disabling complications, which has the potential to further reduce costs and improve outcomes.

Measurement of Disease Activity of Pouchitis.

BACKGROUND: Pouchitis is the most common inflammatory complication in ulcerative colitis patients undergoing postoperative construction of an IPAA. Pouchitis refers to a spectrum of diseases, and as such, it lacks a universally accepted definition as well as validated instruments to measure disease activity and treatment response. Assessing pouchitis activity is challenging, and methods for diagnosis and classification of severity of pouchitis are not universally agreed upon. CLINICAL FEATURES: Pouchitis is characterized by a constellation of clinical symptoms, including increased stool frequency, urgency, incontinence, bleeding, and rarely constitutional symptoms such as malaise and low-grade fever. However, these symptoms are subjective, and similar symptoms can be caused by noninflammatory conditions including anal sphincter dysfunction, anastomotic strictures, occult leaks, pouch inlet obstruction, and cuffitis. Objective scores that include endoscopic and histologic criteria have been developed for subjects with an IPAA. However, these instruments are not validated for measuring pouchitis disease activity and are associated with a number of challenges. In addition, the clinical components of the scores correlate poorly with endoscopic and histologic findings. CONCLUSION AND FUTURE DIRECTIONS: There is a need for prospective studies to facilitate the development and validation of novel instruments that are valid, reliable, and responsive to change that would facilitate the development of therapeutic agents for the treatment of pouchitis.

A Radial Basis Function Neural Network Approach to Predict Preschool Teachers' Technology Acceptance Behavior.

With the continual development of artificial intelligence and smart computing in recent years, quantitative approaches have become increasingly popular as an efficient modeling tool as they do not necessitate complicated mathematical models. Many nations have taken steps, such as transitioning to online schooling, to decrease the harm caused by coronaviruses. Inspired by the demand for technology in early education, the present research uses a radial basis function (RBF) neural network (NN) modeling technique to predict preschool instructors' technology usage in classes based on recognized determinant characteristics of technology acceptance. In this regard, this study utilized the RBFNN approach to predict preschool teachers' technology acceptance behavior, based on the theory of planned behavior, which states that behavioral achievement, in our case the actual technology use in class, depends on motivation, intention and ability, and behavioral control. Thus, this research design is based on an adapted version of the technology acceptance model (TAM) with eight dimensions: D1. Perceived usefulness, D2. Perceived ease of use, D3. Perceived enjoyment, D4. Intention to use, D5. Actual use, D6. Compatibility, D7. Attitude, and D8. Self-efficacy. According to the TAM, actual usage is significantly predicted by the other seven dimensions used in this research. Instead of using the classical multiple linear regression statistical processing of data, we opted for a NN based on the RBF approach to predict the actual usage behavior. This study included 182 preschool teachers who were randomly chosen from a project-based national preschool teacher training program and who responded to our online questionnaire. After designing the RBF function with the actual usage as an output variable and the other seven dimensions as input variables, in the model summary, we obtained in the training sample a sum of squares error of 37.5 and a percent of incorrect predictions of 43.3%. In the testing sample, we obtained a sum of squares error of 14.88 and a percent of incorrect predictions of 37%. Thus, we can conclude that 63% of the classified data are correctly assigned to the models' dependent variable, i.e., actual technology use, which is a significant rate of correct predictions in the testing sample. This high significant percentage of correct classification represents an important result, mainly because this is the first study to apply RBFNN's prediction on psychological data, opening up a new interdisciplinary field of research.

Taking the Next Steps in Endoscopic Visual Assessment of Barrett's Esophagus: A Pilot Study.

PURPOSE: Patients with Barrett's esophagus (BE) undergo surveillance endoscopies to assess for pre-cancerous changes. We developed a simple endoscopic classification method for predicting non-dysplastic BE (NDBE), low-grade dysplasia (LGD)/indefinite for dysplasia (ID) and high-grade dysplasia (HGD)/early esophageal adenocarcinoma (EAC). PATIENTS AND METHODS: Twenty-two patients with BE underwent endoscopy using the PENTAX Medical MagniView gastroscope and OPTIVISTA processor. Sixty-six video-still images were analyzed to characterize the microsurface, microvasculature and the presence of a demarcation line. Class A was characterized by regular microvascular and microsurface patterns and absence of a demarcation line, class B by changes in the microvascular and/or microsurface patterns compared to the background mucosa with presence of a demarcation line, and class C by irregular microvascular and/or irregular microsurface patterns with presence of a demarcation line. RESULTS: Of the class A images, 97.9% were NDBE. For class B, 69.2% were LGD/ID and 30.8% NDBE. One hundred percent of the class C samples were HGD/EAC. The sensitivity of our classification system was 93.8%, specificity 92%, positive predictive value 78.9%, negative predictive value 97.9% and an accuracy 92.4%. CONCLUSION: In this study, we developed a simple classification system for the prediction of NDBE, LGD/ID and HGD/EAC. Its real-time clinical applicability will be validated prospectively.

In search of stool donors: a multicenter study of prior knowledge, perceptions, motivators, and deterrents among potential donors for fecal microbiota transplantation.

Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection. Stool donors are essential, but difficult to recruit and retain. We aimed to identify factors influencing willingness to donate stool. This multi-center study with a 32-item questionnaire targeted young adults and health care workers via social media and university email lists in Edmonton and Kingston, Canada; London and Nottingham, England; and Indianapolis and Boston, USA. Items included baseline demographics and FMT knowledge and perception. Investigated motivators and deterrents included economic compensation, screening process, time commitment, and stool donation logistics. Logistic regression and linear regression models estimated associations of study variables with self-assessed willingness to donate stool. 802 respondents completed our questionnaire: 387 (48.3%) age 21-30 years, 573 (71.4%) female, 323 (40%) health care workers. Country of residence, age and occupation were not associated with willingness to donate stool. Factors increasing willingness to donate were: already a blood donor (OR 1.64), male, altruism, economic benefit, knowledge of how FMT can help patients (OR 1.32), and positive attitudes towards FMT (OR 1.39). Factors decreasing willingness to donate were: stool collection unpleasant (OR 0.92), screening process invasive (OR 0.92), higher stool donation frequency, negative social perception of stool, and logistics of collection/transporting feces. We conclude that 1) blood donors and males are more willing to consider stool donation; 2) altruism, economic compensation, and positive feedback are motivators; and 3) screening process, high donation frequency, logistics of collection/transporting feces, lack of public awareness, and negative social perception are deterrents. Considering these variables could maximize donor recruitment and retention.

Calnexin silencing in mouse neonatal cardiomyocytes induces Ca2+ cycling defects, ER stress, and apoptosis.

Calnexin (CNX) is an endoplasmic reticulum (ER) quality control chaperone that has been implicated in ER stress. ER stress is a prominent pathological feature of various pathologic conditions, including cardiovascular diseases. However, the role of CNX and ER stress has not been studied in the heart. In the present study, we aimed to characterize the role of CNX in cardiomyocyte physiology with respect to ER stress, apoptosis, and cardiomyocyte Ca(2+) cycling. We demonstrated significantly decreased CNX mRNA and protein levels by LentiVector mediated transduction of targeting shRNAs. CNX silenced cardiomyocytes exhibited ER stress as evidenced by increased GRP78 and ATF6 protein levels, increased levels of spliced XBP1 mRNA, ASK-1, ERO1a, and CHOP mRNA levels. CNX silencing also led to significant activation of caspases-3 and -9. This activation of caspases was associated with hallmark morphological features of apoptosis including loss of sarcomeric organization and nuclear integrity. Ca(2+) imaging in live cells showed that CNX silencing resulted in Ca(2+) transients with significantly larger amplitudes but decreased frequency and Ca(2+) uptake rates in the basal state. Interestingly, 5 mM caffeine stimulated Ca(2+) transients were similar between control and CNX silenced cardiomyocytes. Finally, we demonstrated that CNX silencing induced the expression of the L-type voltage dependent calcium channel (CAV1.2) but reduced the expression of the sarcoplasmic reticulum ATPase (SERCA2a). In conclusion, this is the first study to demonstrate CNX has a specific role in cardiomyocyte viability and Ca(2+) cycling through its effects on ER stress, apoptosis and Ca(2+) channel expression.

α-Crystallin B prevents apoptosis after H2O2 exposure in mouse neonatal cardiomyocytes.

α-Crystallin B (cryAB) is the most abundant small heat shock protein in cardiomyocytes (CMs) and has been shown to have potent antiapoptotic properties. Because the mechanism by which cryAB prevents apoptosis has not been fully characterized, we examined its protective effects at the cellular level by silencing cryAB in mouse neonatal CMs using lentivector-mediated transduction of short hairpin RNAs. Subcellular fractionation of whole hearts showed that cryAB is cytosolic under control conditions, and after H(2)O(2) exposure, it translocates to the mitochondria. Phosphorylated cryAB (PcryAB) is mainly associated with the mitochondria, and any residual cytosolic PcryAB translocates to the mitochondria after H(2)O(2) exposure. H(2)O(2) exposure caused increases in cryAB and PcryAB levels, and cryAB silencing resulted in increased levels of apoptosis after exposure to H(2)O(2). Coimmunoprecipitation assays revealed an apparent interaction of both cryAB and PcryAB with mitochondrial voltage-dependent anion channels (VDAC), translocase of outer mitochondrial membranes 20 kDa (TOM 20), caspase 3, and caspase 12 in mouse cardiac tissue. Our results are consistent with the conclusion that the cardioprotective effects of cryAB are mediated by its translocation from the cytosol to the mitochondria under conditions of oxidative stress and that cryAB interactions with VDAC, TOM 20, caspase 3, and caspase 12 may be part of its protective mechanism.