Canadian Celiac Association

Background: Tenecteplase is a genetically-modified variant of the tissue plasminogen activator alteplase, with increased fibrin-specificity, administered as a more convenient intravenous bolus. Recent data, from the AcT trial, have shown tenecteplase to be non-inferior to alteplase in patients with acute ischemic stroke (AIS) treated within 4.5 hours from symptom onset, the direction of effect favoring tenecteplase. As a result, the Heart and Stroke Foundation of Canada has added tenecteplase to the Stroke Best Practice Recommendations. However, its cost-effectiveness in the Canadian setting remains unknown. Methods: An analysis was performed to estimate the cost-effectiveness of tenecteplase compared to alteplase in the AIS population. The model structure combines a decision tree for the first 90 days post index stroke, where the 7 modified Rankin Scale (mRS) states are informed by the AcT trial, and a Markov model for the remainder of the lifetime horizon. Cost and utility values were derived from the literature and public sources. Canadian health care system and hospital perspectives were used. Results: This economic analysis demonstrates that tenecteplase is dominant compared to alteplase, providing more quality-adjusted life years at lower costs. Conclusions: Adding tenecteplase to hospital formularies for AIS would generate savings for the health care system while providing more benefits.

Here, we introduce a new method for efficiently sampling Chlamydomonas reinhardtii and closely related species using a colony PCR-based screen with novel primer sets designed to specifically detect these important model microalgae. To demonstrate the utility of our new method, we collected 130 soil samples from a wide range of habitats in Ontario, Canada and identified 33 candidate algae, which were barcoded by sequencing a region of the rbcL plastid gene. For select isolates, 18S rRNA gene and YPT4 nuclear markers were also sequenced. Based on phylogenetic and haplotype network analyses of these three loci, seven novel isolates were identified as C. reinhardtii, and one additional isolate appeared to be more closely related to C. reinhardtii than any other known species. All seven new C. reinhardtii strains were interfertile with previously collected C. reinhardtii field isolates, validating the effectiveness of our molecular screen.

Background: We reviewed our autoimmune encephalitis neural antibody testing using brain tissue indirect immunofluorescence (TIIF) and cell-based assays (CBAs) after one year. Methods: Samples were tested from March 2019–March 2020 by TIIF and CBA for anti-NMDAR, LGI1, CASPR2, AMPAR, GABA(B)R, DPPX, IgLON5 and GAD65. Weakly positive or positive CBA, with or without corresponding TIIF positivity, was reported positive. Clinical questionnaires were submitted for clinical-serological correlation. Patients with a compatible clinical phenotype and no more likely alternative diagnosis were classified as true-positives, while all others were flagged as possible false-positives. Results: Twenty of 373 patients (5.4%) had a positive neural antibody. All anti-LGI1 (N=4), GAD65 (N=4), and GABA(B)R (N=1) were classified as true-positives. In contrast, only 3/6 anti-CASPR2 and 3/5 anti-NMDAR were classified as true-positives. Among true-positives, 2/4 anti-LGI and 3/3 anti-CASPR2 were positive by CBA only. All possible false-positive results exhibited only weak serum staining by CBA, with negative serum TIIF and negative CSF CBA/TIIF (if available). Conclusions: Clinical sensitivity of CBA seems higher than TIIF for neural antibodies studied herein, but may come at some expense to clinical specificity. Among patients with weak serum staining by CBA, correlation with serum TIIF, CSF CBA/TIIF, and clinical presentation is recommended.

Proximal multi-site phosphorylation is a critical post-translational modification in protein biology. The additive effects of multiple phosphosite clusters in close spatial proximity triggers integrative and cooperative effects on protein conformation and activity. Proximal phosphorylation has been shown to modulate signal transduction pathways and gene expression, and as a result, is implicated in a broad range of disease states through altered protein function and/or localization including enzyme overactivation or protein aggregation. The role of proximal multi-phosphorylation events is becoming increasingly recognized as mechanistically important, although breakthroughs are limited due to a lack of detection technologies. To date, there is a limited selection of facile and robust sensing tools for proximal phosphorylation. Nonetheless, there have been considerable efforts in developing optical chemosensors for the detection of proximal phosphorylation motifs on peptides and proteins in recent years. This review provides a comprehensive overview of optical chemosensors for proximal phosphorylation, with the majority of work being reported in the past two decades. Optical sensors, in the form of fluorescent and luminescent chemosensors, hybrid biosensors, and inorganic nanoparticles, are described. Emphasis is placed on the rationale behind sensor scaffolds, relevant protein motifs, and applications in protein biology.

The Indigenous Action Group (IAG) is an alliance of solidarity between Indigenous and settler faculty at the University of Toronto Mississauga with the Mississaugas of the Credit First Nation (MCFN), whose Treaty lands the campus is located on. This partnership of responsibility supports the MCFN goals of truth (through public knowledge and recognition of their history), and reconciliation (through the support and equitable sustenance of Indigenous pedagogy, knowledge systems, and research methodologies in educational institutions). The IAG has developed a Community-Engaged Learning (CEL) course to bring ontological pluralism to the Academy to legitimize Indigenous knowledges, epistemologies, and involve the placemaking of local Indigenous communities (Tuhiwah Smith, 2012). This second year undergraduate course entitled “Anthropology and Indigenous Peoples of Turtle Island (in Canada)” was developed and implemented by the Indigenous Action Group to prioritize first person voices from the local Indigenous community. We are hoping this diverse educational model will change the discourse in anthropology courses to begin a collective understanding of ongoing power imbalances and oppression in education from colonial mechanisms.

Protein prenylation is a critical mediator in several diseases including cancer and acquired immunodeficiency syndrome (AIDS). Therapeutic intervention has focused primarily on directly targeting the prenyltransferase enzymes, FTase and GGTase I and II. To date, several drugs have advanced to clinical trials and while promising, they have yet to gain approval in a medical setting due to off-target effects and compensatory mechanisms activated by the body which results in drug resistance. While the development of dual inhibitors has mitigated undesirable side effects, potency remains sub-optimal for clinical development. An alternative approach involves antagonizing the upstream mevalonate pathway enzymes, FPPS and GGPPS, which mediate prenylation as well as cholesterol synthesis. The development of these inhibitors presents novel opportunities for dual inhibition of cancer-driven prenylation as well as cholesterol accumulation. Herein, we highlight progress towards the development of inhibitors against the prenylation machinery.