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Objectives: Medical Assistance in Dying (MAiD) has been legal in Canada since June 2016. A person can receive MAiD if their suffering cannot be relieved under conditions that they consider acceptable. Informed consent requires that the person requesting MAiD has received all the information needed to make their decision; that is, medical diagnosis and prognosis, available treatments including palliative care. The evaluation of unbearable suffering is known to be challenging as suffering is often psychological, existential, and social in nature. While interventions to relieve suffering exist, it is unclear how suffering is assessed and addressed in the literature on MAiD practice. No scoping review exists on the topic in Canada. The aim of this study was to understand how the concept of suffering was approached within the Canadian MAiD grey (GL) and scientific (peer‐reviewed) literature (SL), specifically: 1‐ How suffering is defined and assessed in the context of MAiD in Canada and 2‐ Which interventions in response to suffering are recommended within the process of obtaining informed consent for MAiD and throughout the process of MAiD itself. Methods: A scoping review was conducted based on PRISMA‐SR guidelines. SL articles (N = 1027) were identified from a review of 6 databases and GL documents (N = 537) were obtained from the provinces of Quebec, Ontario and British Columbia. Documents were analyzed using NVivo with coding by two‐raters and continuous team discussions. Results: A multidimensional definition of suffering, akin to the concept of total pain, is used. The assessment of suffering is based upon patients' reports. Tools to aid in the assessment are not comprehensively covered. Specific interventions to address suffering were often focused on active listening and the management of physical symptoms. No specific interventions were mentioned and there was no reference to clinical practice guidelines in the grey literature to address other components of suffering. The use of a multidisciplinary approach is suggested without specifying the nature of involvement. Conclusions: Our review indicates that published guidelines of MAID assessments could include clearer structure around the assessment and management of suffering, with suggestions of tools that may help clarify types of suffering and reference to clinical practice guidelines and interventions to holistically attend to patient suffering with an attention on non‐physical symptoms. Guidelines would benefit from clearer explanations of how members of an interdisciplinary teams could be coherently coordinated. [ABSTRACT FROM AUTHOR]

Since its introduction to North America in the early 1900s, white pine blister rust (WPBR) caused by the fungal pathogen Cronartium ribicola has resulted in substantial economic losses and ecological damage to native North American five-needle pine species. The high susceptibility and mortality of these species, including limber pine (Pinus flexilis), creates an urgent need for the development and deployment of resistant germplasm to support recovery of impacted populations. Extensive screening for genetic resistance to WPBR has been underway for decades in some species but has only started recently in limber pine using seed families collected from wild parental trees in the USA and Canada. This study was conducted to characterize Alberta limber pine seed families for WPBR resistance and to develop reliable molecular tools for marker-assisted selection (MAS). Open-pollinated seed families were evaluated for host reaction following controlled infection using C. ribicola basidiospores. Phenotypic segregation for presence/absence of stem symptoms was observed in four seed families. The segregation ratios of these families were consistent with expression of major gene resistance (MGR) controlled by a dominant R locus. Based on linkage disequilibrium (LD)-based association mapping used to detect single nucleotide polymorphism (SNP) markers associated with MGR against C. ribicola , MGR in these seed families appears to be controlled by Cr4 or other R genes in very close proximity to Cr4. These associated SNPs were located in genes involved in multiple molecular mechanisms potentially underlying limber pine MGR to C. ribicola , including NBS-LRR genes for recognition of C. ribicola effectors, signaling components, and a large set of defense-responsive genes with potential functions in plant effector-triggered immunity (ETI). Interactions of associated loci were identified for MGR selection in trees with complex genetic backgrounds. SNPs with tight Cr4-linkage were further converted to TaqMan assays to confirm their effectiveness as MAS tools. This work demonstrates the successful translation and deployment of molecular genetic knowledge into specific MAS tools that can be easily applied in a selection or breeding program to efficiently screen MGR against WPBR in Alberta limber pine populations. [ABSTRACT FROM AUTHOR]

Strawberry mild yellow edge virus (SMYEV) is a member of the genus Potexvirus, family Alphaflexiviridae. It is one of the most common pathogenic viruses infecting cultivated strawberries worldwide. In this study, we investigated the genetic diversity of SMYEV in strawberry fields that were severely affected by strawberry decline disease in the eastern Canadian provinces of New Brunswick, Nova Scotia, Prince Edward Island and Quebec. A total of 134 SMYEV coat protein (CP) gene sequences, representing 85 nucleic acid haplotypes, were identified in 56 field samples. A highly divergent SMYEV population was found in all four provinces, but there was little genetic differentiation among the populations, and moreover, the Canadian SMYEV isolates formed a unique dissimilar, genetically divergent population group when compared to those reported in other countries. Phylogenetic analysis revealed three new SMYEV subclades that consisted mainly of Canadian variants and were composed of 76 sequence haplotypes (76/85, 88%). Mixed infections by different SMYEV variants were observed in 38 samples (38/56, 68%). Evolutionary analysis suggested that the SMYEV strains in eastern Canada possibly originated outside of Canada but adapted to conditions in the region through genetic mutations. [ABSTRACT FROM AUTHOR]

• North American five needle white pines are very susceptible to white pine blister rust (WPBR). • Seedlots with genetic resistance to WPBR are needed for restoration. • The level and type of genetic resistance to WPBR varies greatly by species. • Restoration efforts for some species has begun. • Genomic resources offer promise to develop resistant populations in the future. All nine five-needle white pine species (genus Pinus , subgenus Strobus , subsections Strobus and Balfourianae) native to the U.S. and Canada are highly susceptible to white pine blister rust (WPBR), caused by the non-native fungal pathogen Cronartium ribicola. WPBR is present within the geographic range of eight of the nine species in the U.S. including the four species also present in Canada, but has not yet been documented in Mexico. Genetic resistance to WPBR has been documented in eight of the white pine species present in the U.S., with extensive work on foxtail pine (Pinus balfouriana) just recently started. The development of populations of trees with durable genetic resistance, while also retaining genetic diversity and adaptability, is seen as a fundamental step in restoring white pine species. Major gene resistance (MGR) has been documented in four species, and quantitative resistance (QR) is likely present in all species, but at levels ranging from very low to moderately high. Restoration using seed from WPBR resistant parent trees has been underway for several decades for western white pine (P. monticola), sugar pine (P. lambertiana) , and eastern white pine (P. strobus), and has begun more recently for whitebark pine (P. albicaulis) and limber pine (P. flexilis). For many of these white pine species, locating additional resistant parents and acquiring more seed will be needed over the ensuing decades. The previous efforts in developing populations of trees with genetic resistance to WPBR has used conventional tree improvement techniques of tree selection and seedling inoculation trials. However, in the future with the continued development of omics resources and tools in white pines, biotechnology has the potential to aid resistance programs. Candidate genes have been identified for host MGR, QR, and disease susceptibility (S) to WPBR, as well as for C. ribicola effectors. Marker-assisted selection (MAS) tools developed from MGR-linked genes would be useful to combine MGR and QR, which should improve the potential durability of resistance. Integration of breeding programs with omics information and tools can help pave a road towards improvement of WPBR resistance through biotechnological approaches such as MAS, and genomic selection (GS), or potentially helping to incorporate unique resistance not currently found in North American five-needle white pines. In the near future, these tools could potentially aid in the initial search for candidate trees which would increase the efficiency of developing WPBR resistant populations, as well as defining the extent and distribution of adaptive genetic variation in the species, which will aid in planning restoration efforts. [ABSTRACT FROM AUTHOR]

Safe and effective vaccines are needed to end the COVID-19 pandemic. Here, we report the preclinical development of a lipid nanoparticle–formulated SARS-CoV-2 mRNA vaccine, PTX-COVID19-B. PTX-COVID19-B was chosen among three candidates after the initial mouse vaccination results showed that it elicited the strongest neutralizing antibody response against SARS-CoV-2. Further tests in mice and hamsters indicated that PTX-COVID19-B induced robust humoral and cellular immune responses and completely protected the vaccinated animals from SARS-CoV-2 infection in the lung. Studies in hamsters also showed that PTX-COVID19-B protected the upper respiratory tract from SARS-CoV-2 infection. Mouse immune sera elicited by PTX-COVID19-B vaccination were able to neutralize SARS-CoV-2 variants of concern, including the Alpha, Beta, Gamma, and Delta lineages. No adverse effects were induced by PTX-COVID19-B in either mice or hamsters. Based on these results, PTX-COVID19-B was authorized by Health Canada to enter clinical trials in December 2020 with a phase 2 clinical trial ongoing.

Several prior investigations demonstrate an improvement in bone mineral density associated with use of tumor necrosis factor inhibitors (TNFi). We compared the risk of osteoporotic fractures among patients with rheumatoid arthritis (RA) initiating a disease-modifying antirheumatic drug (DMARD). A population-based cohort study was conducted using health care utilization data (1996-2008) from a Canadian province and a U.S. commercial insurance plan. Patients with at least two RA diagnoses were identified, and follow-up began with the first prescription for a DMARD. Drug regimens were categorized into three mutually exclusive hierarchical groups: (1) TNFi with or without nonbiologic DMARDs (nbDMARD), (2) methotrexate (MTX) without a TNFi, or (3) other nbDMARD without a TNFi or MTX. Main outcomes were hospitalizations for fractures of the hip, wrist, humerus, or pelvis based on diagnoses and procedure codes. The study cohort consisted of 16,412 RA patients with 25,988 new treatment episodes: 5856 TNFi, 12,554 MTX, and 7578 other nbDMARD. The incidence rate per 1000 person-years for osteoporotic fracture were 5.11 [95% confidence interval (CI) 3.50-7.45] for TNFi, 5.35 (95% CI 4.08-7.02) for MTX, and 6.38 (95% CI 3.78-10.77) for other nbDMARD. After multivariable adjustment for osteoporosis and fracture-related risk factors, the risk of nonvertebral osteoporotic fracture was not different in either TNFi [hazard ratio (HR) 1.07, 95% CI 0.57-1.98] or MTX (HR 1.18, 95% CI 0.60-2.34) compared with nbDMARD. Among subjects diagnosed with RA, the adjusted risk of nonvertebral fracture was similar across persons starting a TNFi, MTX, or other nbDMARD., (Copyright © 2012 American Society for Bone and Mineral Research.)

Context: Rheumatoid arthritis (RA) and psoriasis have been linked with insulin resistance and diabetes mellitus (DM). Prior investigations suggest that systemic immunosuppressive drugs may improve insulin resistance and reduce the risk of DM., Objective: To compare the risk of newly recorded DM among participants diagnosed with RA or psoriasis based on use of a variety of disease-modifying antirheumatic drugs (DMARDs)., Design, Setting, and Participants: A retrospective cohort study among 121,280 patients with a diagnosis of either RA or psoriasis on at least 2 visits. The analyses were conducted in the context of 2 large health insurance programs, 1 in Canada and 1 in the United States, using administrative data. The mean follow-up was 5.8 months and began with the first prescription for a DMARD after study eligibility was met. Drug regimens were categorized into 4 mutually exclusive groups: (1) tumor necrosis factor (TNF) inhibitors with or without other DMARDs; (2) methotrexate without TNF inhibitors or hydroxychloroquine; (3) hydroxychloroquine without TNF inhibitors or methotrexate; or (4) other nonbiologic DMARDs without TNF inhibitors, methotrexate, or hydroxychloroquine (reference exposure)., Main Outcome Measure: Newly recorded DM as evidenced by a new diagnosis of DM with use of a DM-specific medication., Results: The study cohort consisted of 13,905 participants with 22,493 treatment episodes starting 1 of the categories of DMARD regimens between January 1996 and June 2008. New diabetes cases and respective incidence rates per 1000 person-years were: other nonbiologic DMARDs (55 cases among 3993 treatment episodes; rate, 50.2; 95% confidence interval [CI], 47.3-53.2); TNF inhibitors (80 cases among 4623 treatment episodes; rate, 19.7; 95% CI, 19.1-20.3); methotrexate (82 cases among 8195 treatment episodes; rate, 23.8; 95% CI, 23.0-24.6); and hydroxychloroquine (50 cases among 5682 treatment episodes; rate, 22.2; 95% CI, 21.3-23.1). The multivariate adjusted hazard ratios for DM were 0.62 (95% CI, 0.42-0.91) for TNF inhibitors, 0.77 (95% CI, 0.53-1.13) for methotrexate, and 0.54 (95% CI, 0.36-0.80) for hydroxychloroquine compared with other nonbiologic DMARDS., Conclusion: Among patients with RA or psoriasis, the adjusted risk of DM was lower for individuals starting a TNF inhibitor or hydroxychloroquine compared with initiation of other nonbiologic DMARDs.