Identifying training needs of healthcare providers to implement caries risk assessment

BackgroundEarly childhood caries remains a pressing concern among Indigenous children in Canada, driven by systemic inequities, limited access to care, and fragmented service delivery. Integrating caries risk assessment (CRA) into primary care presents an opportunity to improve early detection and prevention. This study explored the training needs and preferred delivery methods of non-dental primary care providers (NDPCPs) to support CRA implementation in Indigenous pediatric settings.MethodsThis qualitative exploratory study involved 50 NDPCPs serving First Nations and Métis children under six years of age across 10 communities in Manitoba. Data were collected between April 2023 and February 2025 through eight focus groups and 12 key informant interviews, followed by brief individual interviews to assess preferred training modalities. Transcripts were analyzed using thematic analysis to identify key training needs and preferences.ResultsParticipants included physicians, nurse practitioners, public health nurses, physician assistants, dietitians, and child development workers. Four core training areas were identified: dental caries screening, CRA tool usage, fluoride varnish application, and documentation/referral processes. An additional cross-cutting theme emphasized the importance of culturally safe and trauma-informed training. Despite recognizing the CRA tool's value and ease of use, participants reported limited formal training in preventive oral health and stressed the need for hands-on, culturally appropriate instruction. Preferred training modalities varied by geography: urban providers favored blended in-person and online approaches, while rural providers preferred online formats due to travel constraints. Overall, in-person and interactive training was most preferred.ConclusionNDPCPs require structured, context-specific training to effectively integrate CRA into routine care. A hybrid training model combining online modules with locally delivered, hands-on learning may best address geographic and resource-based disparities. Training content should be simple, skill-focused, and culturally responsive to support NDPCPs in delivering equitable oral healthcare to Indigenous children

Site-Directed Mutations and the Polymorphic Variant Ala160Thr in the Human Thromboxane Receptor Uncover a Structural Role for Transmembrane Helix 4

The human thromboxane A2 receptor (TP), belongs to the prostanoid subfamily of Class A GPCRs and mediates vasoconstriction and promotes thrombosis on binding to thromboxane (TXA2). In Class A GPCRs, transmembrane (TM) helix 4 appears to be a hot spot for non-synonymous single nucleotide polymorphic (nsSNP) variants. Interestingly, A160T is a novel nsSNP variant with unknown structure and function. Additionally, within this helix in TP, Ala1604.53 is highly conserved as is Gly1644.57. Here we target Ala1604.53 and Gly1644.57 in the TP for detailed structure-function analysis. Amino acid replacements with smaller residues, A160S and G164A mutants, were tolerated, while bulkier beta-branched replacements, A160T and A160V showed a significant decrease in receptor expression (Bmax). The nsSNP variant A160T displayed significant agonist-independent activity (constitutive activity). Guided by molecular modeling, a series of compensatory mutations were made on TM3, in order to accommodate the bulkier replacements on TM4. The A160V/F115A double mutant showed a moderate increase in expression level compared to either A160V or F115A single mutants. Thermal activity assays showed decrease in receptor stability in the order, wild type>A160S>A160V>A160T>G164A, with G164A being the least stable. Our study reveals that Ala1604.53 and Gly1644.57 in the TP play critical structural roles in packing of TM3 and TM4 helices. Naturally occurring mutations in conjunction with site-directed replacements can serve as powerful tools in assessing the importance of regional helix-helix interactions

Diversity of structures and properties among catalases

More than 300 catalase sequences are now available, divided among monofunctional catalases (> 225), bifunctional catalase-peroxidases (> 50) and manganese-containing catalases (> 25). When combined with the recent appearance of crystal structures from at least two representatives from each of these groups (nine from the monofunctional catalases), valuable insights into the catalatic reaction mechanism in its various forms and into catalase evolution have been gained. The structures have revealed an unusually large number of modifications unique to catalases, a result of interacting with reactive oxygen species. Biochemical and physiological characterization of catalases from many different organisms has revealed a surprisingly wide range of catalatic efficiencies, despite similar sequences. Catalase gene expression in micro-organisms generally is controlled either by sensors of reactive oxygen species or by growth phase regulons, although the detailed mechanisms vary considerably.Preparation of this manuscript was supported by Grant OGP9600 from the Natural Sciences and Engineering Research Council of Canada to P. C. LoewenPeer Reviewe

Advanced Glycation End-Products Can Activate or Block Bitter Taste Receptors

Bitter taste receptors (T2Rs) are expressed in several tissues of the body and are involved in a variety of roles apart from bitter taste perception. Advanced glycation end-products (AGEs) are produced by glycation of amino acids in proteins. There are varying sources of AGEs, including dietary food products, as well as endogenous reactions within our body. Whether these AGEs are T2R ligands remains to be characterized. In this study, we selected two AGEs, namely, glyoxal-derived lysine dimer (GOLD) and carboxymethyllysine (CML), based on their predicted interaction with the well-studied T2R4, and its physiochemical properties. Results showed predicted binding affinities (Kd) for GOLD and CML towards T2R4 in the nM and μM range, respectively. Calcium mobilization assays showed that GOLD inhibited quinine activation of T2R4 with IC50 10.52 ± 4.7 μM, whilst CML was less effective with IC50 32.62 ± 9.5 μM. To characterize whether this antagonism was specific to quinine activated T2R4 or applicable to other T2Rs, we selected T2R14 and T2R20, which are expressed at significant levels in different human tissues. A similar effect of GOLD was observed with T2R14; and in contrast, GOLD and CML activated T2R20 with an EC50 of 79.35 ± 29.16 μM and 65.31 ± 17.79 μM, respectively. In this study, we identified AGEs as novel T2R ligands that caused either activation or inhibition of different T2Rs.</jats:p