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Sonia Grzelak,1,2 Mélanie Bérubé,1,2 Marc-Aurèle Gagnon,1 Caroline Côté,1,2 Valérie Turcotte,3 Stéphane Pelet,4 Étienne Belzile4 1Population Health and Optimal Practices Research Unit (Trauma - Emergency - Critical Care Medicine), Laval University Research Center (Hôpital de l’Enfant-Jésus), Quebec City, QC, Canada; 2Faculty of Nursing, Laval University, Quebec City, QC, Canada; 3Nursing Department, CIUSSS du Nord-de-l’Île-de-Montréal, Hôpital du Sacré-Coeur de Montréal, Montréal, QC, Canada; 4Department of Orthopedic Surgery, CHU de Québec-Université Laval (Hôpital de l’Enfant-Jésus), Quebec City, QC, CanadaCorrespondence: Sonia GrzelakPopulation Health and Optimal Practices Research Unit, Laval University Research Center (Hôpital de l’Enfant-Jésus), 1401, 18 e rue, Quebec City, QC, G1V 1Z4, Canada, Tel +1 418 649-0252, ext 66600, Fax +1 418-649-5733, Email sonia.grzelak.1@ulaval.caPurpose: To examine 1) pain management strategies within the care trajectory of orthopaedic trauma patients and patients’ perception of their effectiveness, 2) adverse effects (AEs) associated with pharmacological treatments, particularly opioids and cannabis, and 3) patients’ perceptions of strategies that should be applied after an orthopaedic trauma and support that they should obtain from health professionals for their use.Patients and Methods: This study was conducted with orthopaedic trauma patients in a level 1 trauma center. A convergent mixed-methods design was used. Data on pain experience, pain management strategies used and AEs were collected with self-administered questionnaires at hospital discharge (T1) and at 3 months after injury (T2). Patients’ preferences about the pain management strategies used, the required support and AEs were further examined through semi-structured individual interviews at the same time measures. Descriptive statistics and thematic analyses were performed.Results: Seventy-one patients were recruited and 30 individual interviews were undertaken. Pharmacological pain management strategies used at T1 and T2 were mainly opioids (95.8%; 20.8%) and acetaminophen (91.5%; 37.5%). The most frequently applied non-pharmacological strategies were sleep (95.6%) and physical positioning (89.7%) at T1 and massage (46.3%) and relaxation (32.5%) at T2. Findings from quantitative and qualitative analyses highlighted that non-pharmacological strategies, such as comfort, massage, distraction, and physical therapy, were perceived as the most effective by participants. Most common AEs related to opioids were dry mouth (78.8%) and fatigue (66.1%) at T1 and insomnia (30.0%) and fatigue (20.0%) at T2. Dry mouth (28.6%) and drowsiness (14.3%) were the most reported AEs by patients using recreational cannabis. An important need for information at hospital discharge and for a personalized follow-up was identified by participants during interviews.Conclusion: Despite its AEs, we found that opioids are still the leading pain management strategy after an orthopaedic trauma and that more efforts are needed to implement non-pharmacological strategies. Cannabis was taken for recreational purposes but patients also used it for pain relief. Support from health professionals is needed to promote the adequate use of these strategies.Keywords: orthopaedic trauma, pain, pharmacological strategies, non-pharmacological strategies, opioids, cannabis

Abstract Background Telomeres, the protective cap of chromosomes, have emerged as powerful markers of biological age and life history in model and non-model species. The qPCR method for telomere length estimation is one of the most common methods for telomere length estimation, but has received recent critique for being too error-prone and yielding unreliable results. This critique coincides with an increasing awareness of the potentials and limitations of the qPCR technique in general and the proposal of a general set of guidelines (MIQE) for standardization of experimental, analytical, and reporting steps of qPCR. In order to evaluate the utility of the qPCR method for telomere length estimation in non-model species, we carried out four different qPCR assays directed at humpback whale telomeres, and subsequently performed a rigorous quality control to evaluate the performance of each assay. Results Performance differed substantially among assays and only one assay was found useful for telomere length estimation in humpback whales. The most notable factors causing these inter-assay differences were primer design and choice of using singleplex or multiplex assays. Inferred amplification efficiencies differed by up to 40% depending on assay and quantification method, however this variation only affected telomere length estimates in the worst performing assays. Conclusion Our results suggest that seemingly well performing qPCR assays may contain biases that will only be detected by extensive quality control. Moreover, we show that the qPCR method for telomere length estimation can be highly precise and accurate, and thus suitable for telomere measurement in non-model species, if effort is devoted to optimization at all experimental and analytical steps. We conclude by highlighting a set of quality controls which may serve for further standardization of the qPCR method for telomere length estimation, and discuss some of the factors that may cause variation in qPCR experiments.

Abstract Background The creation of successful health policy and location of resources increasingly relies on evidence-based decision-making. The development of intuitive, accessible tools to analyse, display and disseminate spatial data potentially provides the basis for sound policy and resource allocation decisions. As health services are rationalized, the development of tools such graphical user interfaces (GUIs) is especially valuable at they assist decision makers in allocating resources such that the maximum number of people are served. GIS can used to develop GUIs that enable spatial decision making. Results We have created a Web-based GUI (wGUI) to assist health policy makers and administrators in the Canadian province of British Columbia make well-informed decisions about the location and allocation of time-sensitive service capacities in rural regions of the province. This tool integrates datasets for existing hospitals and services, regional populations and road networks to allow users to ascertain the percentage of population in any given service catchment who are served by a specific health service, or baskets of linked services. The wGUI allows policy makers to map trauma and obstetric services against rural populations within pre-specified travel distances, illustrating service capacity by region. Conclusion The wGUI can be used by health policy makers and administrators with little or no formal GIS training to visualize multiple health resource allocation scenarios. The GUI is poised to become a critical decision-making tool especially as evidence is increasingly required for distribution of health services.

Background: Norovirus (NoV) is the most common cause of diarrheal episodes globally. Issues with in vitro cultivation systems, genetic variation, and animal models have hindered vaccine development. Plant-derived virus-like particles (VLPs) may address some of these concerns because they are highly immunogenic, can be administered by different routes, and can be rapidly produced to accommodate emerging viral strains., Methods: NoV VLPs (NoVLP) composed of the surface viral protein (VP) 1 of the GI and GII genogroups were produced in Nicotiana benthamiana using an Agrobacterium tumefaciens-based recombinant transient expression system. Leaves from infiltrated plants were harvested and NoVLPs were extracted and purified. The safety and immunogenicity of the GII.4 NoVLP, the genotype currently causing most human disease, were subsequently examined in rabbits and mice., Results: Fifteen GI and GII NoVLPs were successfully expressed in N. benthamiana and were structurally similar to NoV virions, as determined by cryogenic transmission electron microscopy. The NoVLP was well-tolerated, with no local or systemic signs of toxicity in rabbits. Three intramuscular doses of the GII.4 NoVLP adjuvanted with aluminum hydroxide induced robust IgG titers, IgG-secreting cells, histo-blood group antigen blocking titers, and IFNγ-secreting T cells in mice. In addition to circulating antibodies, oral administration of the NoVLP in mice induced significant IgA levels in feces, indicative of a mucosal response., Conclusions: The plant-made NoVLP vaccine was safe and immunogenic in mice and rabbits. Multi-modal vaccination, combining oral and intramuscular administration could be considered for future clinical development to maximize systemic and mucosal immune responses., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: GA, DB, MAD, BJW, MMC, MD, POL, SP, and ST are employees of Medicago Inc. JS is employee of the Center for Vaccine Preventable Diseases, Dalla Lana School of Public Health, University of Toronto, ON, Canada, where she is supported by a postdoctoral fellowship from the Canadian Immunization Research Network. HH is employee of Research Institute of the McGill University Health Centre (under MITACS Elevate post-doctorate fellowship), Montreal, QC, Canada. MB and CD are employees of Providence Therapeutics. NL is employee of PharmaJet, CO, USA., (Copyright © 2023. Published by Elsevier Ltd.)