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Abstract Background Burn injuries are a significant public health concern, closely linked to housing conditions and socioeconomic status. Residents in socioeconomically deprived neighbourhoods are at increased risk of exposure to hazards due to older and poorer housing conditions and limited access to fire protection measures. Individual behaviours such as substance use, smoking, and hoarding are often highlighted as primary causes of residential fires, overshadowing the broader socioeconomic and structural factors that also play a significant role in housing safety. This paper explores the correlation between inadequate housing conditions and heightened fire risks leading to burn injuries, focusing on the contextual factors shaping everyday urban fire risks, experiences, and responses of residents living in Single-Room Occupancy (SRO) housing in Vancouver’s Downtown East Side (DTES) and staff working in the fire, health, housing (social and private), and non-profit sectors. Methods As part of an ongoing ethnographic study, we partnered with the Vancouver Fire Rescue Services (VFRS) to conduct participant observations in private, non-profit, and government-owned SROs, modular homes, and a temporary shelter. This paper synthesizes insights from participant observations from the first author’s self-reflexive journals, including informal conversations with approximately fifty-nine individuals such as SRO tenants, SRO managers/caretakers, health workers, burn survivors, municipal staff, not-for-profit staff, and firefighters. Results Urgent housing-related issues contributing to inequitable everyday urban fire risks were identified, such as structural deficiencies in SRO buildings and systems, inadequate waste management and storage, and inequitable approaches to addressing hoarding. Additionally, disparities in access to information and the interaction between interpersonal and structural stigmas were significant factors, underscoring the pressing need for intervention. Conclusion Communities like DTES, facing precarious housing conditions, disadvantaged neighbourhoods, and complex health and social challenges, necessitate a comprehensive and holistic approach to fire prevention and safety. Recognizing the interplay between housing instability, mental and physical health issues, unregulated toxic drug supply, drug criminalization, and structural inequities allows practitioners from various sectors to develop contextually driven fire prevention strategies. This multifaceted approach transcends individual-level behaviour change and is crucial for addressing the complex issues contributing to fire risks in underserved communities.

Background: During the COVID-19 pandemic, it was hypothesized that stay-at-home policies would impact cases of violence, abuse, and neglect among children and youth due to increased familial stressors. Objective: We examined the effect of the implementation of pandemic policies on violence-related emergency department (ED) visits and hospitalizations among youth. Participants: Violence-related ED visits and hospitalizations among children and youth ages 0–19 in Ontario, Canada were obtained from April 2015 until the most recent available date, March 31, 2022. Methods: We used an interrupted time series design to model the change in monthly violence-related ED visits and hospitalizations before and during the pandemic. We used negative binomial models to estimate the immediate effect of the policy and the change in the number of injuries during the pandemic. Results: After adjusting for seasonality and population changes over our study period, we observed a 56% decrease in violence-related ED visits (RR: 0.44, 95%CI: 0.38, 0.50) and a 35% decrease in hospitalizations (RR: 0.65, 95%CI: 0.52, 0.82) immediately after the implementation of the pandemic policy, followed by moderate increasing trends. We observed no difference in the effect of the pandemic policies on the rate of violence-related ED visits and hospitalizations by sex, age or material deprivation; however, males aged 10–19 years and those in higher quintiles of material deprivation had higher average rates of injuries compared to females, those in younger age groups and lower quintiles of deprivation over the study period. Conclusions: We observed an abrupt decrease in the rate of violence-related ED visits and hospitalizations immediately after the onset of pandemic policies in Ontario. Following this, violence-related injuries increased, approaching pre-pandemic levels.

Abstract Background Social determinants of health (SDH), including “the conditions in which individuals are born, grow, work, live and age” affect child health and well-being. Several studies have synthesized evidence about the influence of SDH on childhood injury risks and outcomes. However, there is no systematic evidence about the impact of SDH on accessing care and quality of care once a child has suffered an injury. We aim to evaluate the extent to which access to care and quality of care after injury are affected by children and adolescents’ SDH. Methods Using Cochrane methodology, we will conduct a systematic review including observational and experimental studies evaluating the association between social/material elements contributing to health disparities, using the PROGRESS-Plus framework: place of residence, race/ethnicity/culture/language, occupation, gender/sex, religion, education, socioeconomic status, and social capital and care received by children and adolescents (≤ 19 years of age) after injury. We will consult published literature using PubMed, EMBASE, CINAHL, PsycINFO, Web of Science, and Academic Search Premier and grey literature using Google Scholar from their inception to a maximum of 6 months prior to submission for publication. Two reviewers will independently perform study selection, data extraction, and risk of bias assessment for included studies. The risk of bias will be assessed using the ROBINS-E and ROB-2 tools respectively for observational and experimental study designs. We will analyze data to perform narrative syntheses, and if enough studies are identified, we will conduct a meta-analysis using random effects models. Discussion This systematic review will provide a synthesis of evidence on the association between SDH and pediatric trauma care (access to care and quality of care) that clinicians and policymakers can use to better tailor care systems and promote equitable access and quality of care for all children. We will share our findings through clinical rounds, conferences, and publication in a peer-reviewed journal. Systematic review registration PROSPERO CRD42023408467

BackgroundInjuries are among the leading causes for hospitalizations and emergency department (ED) visits. COVID-19 restrictions ensured safety to Canadians, but also negatively impacted health outcomes, including increasing rates of certain injuries. These differences in trends have been reported internationally however the evidence is scattered and needs to be better understood to identify opportunities for public education and to prepare for future outbreaks.ObjectiveA scoping review was conducted to synthesize evidence regarding the impact of COVID-19 restrictions on unintentional injuries in Canada, compared to other countries.MethodsStudies investigating unintentional injuries among all ages during COVID-19 from any country, published in English between December 2019 and July 2021, were included. Intentional injuries and/or previous pandemics were excluded. Four databases were searched (MEDLINE, Embase, Web of Science, SPORTDiscus), and a gray literature search was also conducted.ResultsThe search yielded 3,041 results, and 189 articles were selected for extraction. A total of 41 reports were included from the gray literature search. Final studies included research from: Europe (n = 85); North America (n = 44); Asia (n = 32); Oceania (n = 12); Africa (n = 8); South America (n = 4); and multi-country (n = 4). Most studies reported higher occurrence of injuries/trauma among males, and the average age across studies was 46 years. The following mechanisms of injury were reported on most frequently: motor vehicle collisions (MVCs; n = 134), falls (n = 104), sports/recreation (n = 65), non-motorized vehicle (n = 31), and occupational (n = 24). Injuries occurring at home (e.g., gardening, home improvement projects) increased, and injuries occurring at schools, workplaces, and public spaces decreased. Overall, decreases were observed in occupational injuries and those resulting from sport/recreation, pedestrian-related, and crush/trap incidents. Decreases were also seen in MVCs and burns, however the severity of injury from these causes increased during the pandemic period. Increases were observed in poisonings, non-motorized vehicle collisions, lacerations, drownings, trampoline injuries; and, foreign body ingestions.ImplicationsFindings from this review can inform interventions and policies to identify gaps in public education, promote safety within the home, and decrease the negative impact of future stay-at-home measures on unintentional injury among Canadians and populations worldwide.

Introduction Improving sustainable transportation options will help cities tackle growing challenges related to population health, congestion, climate change and inequity. Interventions supporting active transportation face many practical and political hurdles. Implementation science aims to understand how interventions or policies arise, how they can be translated to new contexts or scales and who benefits. Sustainable transportation interventions are complex, and existing implementation science frameworks may not be suitable. To apply and adapt implementation science for healthy cities, we have launched our mixed-methods research programme, CapaCITY/É. We aim to understand how, why and for whom sustainable transportation interventions are successful and when they are not.Methods and analysis Across nine Canadian municipalities and the State of Victoria (Australia), our research will focus on two types of sustainable transportation interventions: all ages and abilities bicycle networks and motor vehicle speed management interventions. We will (1) document the implementation process and outcomes of both types of sustainable transportation interventions; (2) examine equity, health and mobility impacts of these interventions; (3) advance implementation science by developing a novel sustainable transportation implementation science framework and (4) develop tools for scaling up and scaling out sustainable transportation interventions. Training activities will develop interdisciplinary scholars and practitioners able to work at the nexus of academia and sustainable cities.Ethics and dissemination This study received approval from the Simon Fraser University Office of Ethics Research (H22-03469). A Knowledge Mobilization Hub will coordinate dissemination of findings via a website; presentations to academic, community organisations and practitioner audiences; and through peer-reviewed articles.

Abstract Background Concerns regarding health equity (HE) and the built environment (BE) are well established in the Canadian urban context. Transport and injury prevention professionals across sectors, such as transportation and public health, are involved in designing and implementing BE interventions that enhance the safety of vulnerable road users (VRUs). Results from a larger study examining barriers and facilitators to BE change are used to illustrate how transport and injury prevention professionals perceive HE concerns in their work in five Canadian municipalities. Broadening our understanding of how HE influences the professional BE change context is crucial when advocating for modifications that enhance the safety of equity-deserving VRUs and groups who experience marginalization. Methods Interview and focus group data were gathered from transport and injury prevention professionals working in policy/decision-making, transport, police services, public health, non-profit organizations, schools/school boards, community associations, and private sectors across five Canadian urban municipalities: Vancouver, Calgary, Peel Region, Toronto, and Montréal. Data were analyzed using thematic analysis (TA) to illustrate how equity considerations were perceived and applied in participants’ BE change work. Results The results of this study illustrate transport and injury prevention professionals’ awareness of the varying needs of VRUs, as well as the inadequacies of current BEs in the Canadian urban context and consultation processes utilized to guide change. Participants emphasized the importance of equitable community consultation strategies, as well as specific BE changes that would support the health and safety of VRUs. Overall, the results highlight how HE concerns inform transport and injury prevention professionals’ BE change work in the Canadian urban context. Conclusion For professionals working in urban Canadian transport and injury prevention sectors HE concerns influenced their perspectives of the BE and BE change. These results illustrate a growing need for HE to guide BE change work and consultation processes. Further, these results contribute to ongoing efforts in the Canadian urban context to ensure that HE is at the forefront of BE policy change and decision-making, while promoting existing strategies to ensure that the BE, and related decision-making processes, are accessible and informed by a HE lens.

Background Post-translational modification of proteins has the potential to alter the ability of T cells to recognize major histocompatibility complex (MHC) class -I and class-II restricted antigens, thereby resulting in altered immune responses. One such modification is carbamylation (homocitrullination) that results in the formation of homocitrulline (Hcit) residues in a non-enzymatic reaction of cyanate with the lysine residues in the polypeptide chain. Homocitrullination occurs in the tumor microenvironment and CD4-mediated immune responses to Hcit epitopes can target stressed tumor cells and provide a potent antitumor response in mouse models.Methods Homocitrullinated peptides were identified and assessed in vitro for HLA-A2 binding and in vivo in human leukocyte antigen (HLA) transgenic mouse models for immunogenicity. CD8 responses were assessed in vitro for cytotoxicity and in vivo tumor therapy. Human tumor samples were analyzed by targeted mass spectrometry for presence of homocitrullinated peptides.Results Homocitrullinated peptides from aldolase and cytokeratin were identified, that stimulated CD8-mediated responses in vivo. Modified peptides showed enhanced binding to HLA-A2 compared with the native sequences and immunization of HLA-A2 transgenic mice generated high avidity modification specific CD8 responses that killed peptide expressing target cells. Importantly, in vivo the homocitrullinated aldolase specific response was associated with efficient CD8 dependent antitumor therapy of the aggressive murine B16 tumor model indicating that this epitope is naturally presented in the tumor. In addition, the homocitrullinated aldolase epitope was also detected in human tumor samples.Conclusion This is the first evidence that homocitrullinated peptides can be processed and presented via MHC-I and targeted for tumor therapy. Thus, Hcit-specific CD8 T-cell responses have potential in the development of future anticancer therapy.

Video analysis is a useful tool for injury surveillance in rugby union. There are few video analysis studies in the professional female game, with most studies published in the male elite/professional settings. Moreover, there is a sparsity of literature in youth rugby settings. The following narrative review outlines the strengths and limitations of the current video analysis literature for injury surveillance in youth rugby union, highlights the importance of video analysis for youth rugby player safety and welfare, and discusses recommendations for using video analysis to inform player safety in youth rugby.

The rare A673T variant was the first variant found within the amyloid precursor protein (APP) gene conferring protection against Alzheimer's disease (AD). Thereafter, different studies have discovered that the carriers of the APP A673T variant show reduced levels of amyloid beta (Aβ) in the plasma and better cognitive performance at high age. Here, we analyzed cerebrospinal fluid (CSF) and plasma of APP A673T carriers and control individuals using a mass spectrometry-based proteomics approach to identify differentially regulated targets in an unbiased manner. Furthermore, the APP A673T variant was introduced into 2D and 3D neuronal cell culture models together with the pathogenic APP Swedish and London mutations. Consequently, we now report for the first time the protective effects of the APP A673T variant against AD-related alterations in the CSF, plasma, and brain biopsy samples from the frontal cortex. The CSF levels of soluble APPβ (sAPPβ) and Aβ42 were significantly decreased on average 9–26% among three APP A673T carriers as compared to three well-matched controls not carrying the protective variant. Consistent with these CSF findings, immunohistochemical assessment of cortical biopsy samples from the same APP A673T carriers did not reveal Aβ, phospho-tau, or p62 pathologies. We identified differentially regulated targets involved in protein phosphorylation, inflammation, and mitochondrial function in the CSF and plasma samples of APP A673T carriers. Some of the identified targets showed inverse levels in AD brain tissue with respect to increased AD-associated neurofibrillary pathology. In 2D and 3D neuronal cell culture models expressing APP with the Swedish and London mutations, the introduction of the APP A673T variant resulted in lower sAPPβ levels. Concomitantly, the levels of sAPPα were increased, while decreased levels of CTFβ and Aβ42 were detected in some of these models. Our findings emphasize the important role of APP-derived peptides in the pathogenesis of AD and demonstrate the effectiveness of the protective APP A673T variant to shift APP processing towards the non-amyloidogenic pathway in vitro even in the presence of two pathogenic mutations.

ObjectivesThis study explored how demographic characteristics, life experiences, and firefighting exposures have an impact on cancer among female firefighters, and described the types and biologic characteristics of cancers as reported by women in the fire service.MethodsThe online survey was available from June 2019 to July 2020. Questions related to demographic characteristics, lifestyle factors, firefighting exposures, and cancer diagnoses. Descriptive analyses characterized variables by the presence or absence of cancer. Qualitative data provided insight into both firefighting and cancer experiences among women.ResultsThere were 1,344 female firefighter respondents from 12 different countries, 256 of whom provided information on their cancer diagnosis. North American respondents made up 92% of the total. Those with cancer were older, had been in the fire service longer, had more career fires and toxic exposures, and were less likely to still be in active service. They also reported more tobacco use, and more full-term pregnancies. There were no differences in family history of cancer between the two groups. The average age at diagnosis was 39.0 years. The major types of cancer reported included breast (25.4%), cervical (21.1%), melanoma (20.7%), base cell/skin (16.4%), and uterine (14.8%). The cancer was detected when seeking medical attention for symptoms (42.1%), during routine health screening (29.8%), and during specific cancer screening (28.1%). The stage of cancer was reported by 44.5%, and 30.9% included the histopathological grade. Treatments included surgery (72.7%), chemotherapy (14.8%), radiotherapy (13.7%), and observation (13.7%). Challenges associated with cancer included psychosocial (33.2%), financial (18.8%), physical (6.6%), and spiritual (6.3%). Concerns about reporting a cancer experience to their employer included the desire to keep health information private (11.3%), a feeling of vulnerability (7.4%), and being perceived as weak (7.0%). Lack of support from their employer or insurer was also noted.ConclusionFemale firefighters experienced a wide variety of different types of cancers which may come earlier than similar cancers in the public. These findings can help inform resource allocation, the development of new policies, and the need for broader presumptive coverage to support female firefighters diagnosed with cancer.

IntroductionThis study aimed to quantify the total cost of violent firearm-related offenses in British Columbia in 2016 Canadian dollars over a five-year period, 2012 to 2016. The purposes of this study were to estimate the direct costs to the health care system and indirect costs to society for violent firearm injuries and deaths; and to estimate criminal justice system costs pertaining to firearm incidents.MethodsHuman and economic costs to the health care system and productivity losses were calculated using health administrative datasets such as B.C. Vital Statistics and Discharge Abstract Database. Criminal justice system costs pertaining to firearm incidents were estimated by applying weighted average costs to aggregate expenditures using methodology consistent with that used by Statistics Canada.ResultsThere was a total of 108 deaths and 245 hospitalizations resulting from violent firearm injuries. The total estimated cost of all violent firearm crime averaged $294,378,985 per year; human costs averaged $188,416,841 per year, where health care costs averaged $3,910,317 per year, productivity losses from workforce and household averaged $17,299,054 and $4,559,470 per year, respectively, and loss of life averaged $162,648,000; and $105,021,145 in criminal justice system costs, and $941,000 in programming costs.ConclusionThis study clearly demonstrates the significant cost of violent firearm injury in British Columbia and the impacts on the health care system, criminal justice system, and to society at large, particularly within the criminal justice system where the costs were significantly higher than health care.

Hypoxic-ischaemic encephalopathy (HIE) is an important cause of morbidity and mortality globally. Although mild therapeutic hypothermia (TH) may improve outcomes in selected babies, the mechanism of action is not fully understood. A proteomics discovery study was carried out to analyse proteins in the plasma of newborns with HIE. Proteomic analysis of plasma from 22 newborns with moderate-severe HIE that had initially undergone TH, and relative controls including 10 newborns with mild HIE who did not warrant TH and also cord blood from 10 normal births (non-HIE) were carried out using the isobaric Tandem Mass Tag (TMT®) 10plexTM labelling with tandem mass spectrometry. A total of 7818 unique peptides were identified in all TMT10plexTM samples, translating to 3457 peptides representing 405 proteins, after applying stringent filter criteria. Apart from the unique protein signature from normal cord blood, unsupervised analysis revealed several significantly regulated proteins in the TH-treated moderate-severe HIE group. GO annotation and functional clustering revealed various proteins associated with glucose metabolism: the enzymes fructose-bisphosphate aldolase A, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate mutase 1, phosphoglycerate kinase 1, and pyruvate kinase PKM were upregulated in newborns with favourable (sHIE+) outcomes compared to newborns with unfavourable (sHIE−) outcomes. Those with favourable outcomes had normal MR imaging or mild abnormalities not predictive of adverse outcomes. However, in comparison to mild HIE and the sHIE− groups, the sHIE+ group had the additional glucose metabolism-related enzymes upregulated, including triosephosphate isomerase, α-enolase, 6-phosphogluconate dehydrogenase, transaldolase, and mitochondrial glutathione reductase. In conclusion, our plasma proteomic study demonstrates that TH-treated newborns with favourable outcomes have an upregulation in glucose metabolism. These findings may open new avenues for more effective neuroprotective therapy.

IntroductionCanada’s opioid crisis has taken thousands of lives, increasing awareness of poisoning-related injuries as an important public health issue. However, in British Columbia (BC), where overdose mortality rates are the highest in Canada, studies have not yet identified which demographic populations most often visit emergency departments (ED) due to all poisonings, nor which substances are most commonly involved. The aim of this study was to explore these gaps, after developing a methodology for calculating ED visit rates in BC. MethodsPoisoning-related ED visit rates during fiscal years 2012/13 to 2016/17, inclusive, were calculated by sex, age group, poisoning substance and socioeconomic status, using a novel methodology developed in this study. ED data were sourced from the National Ambulatory Care Reporting System and population data from Statistics Canada’s 2016 (or 2011) census profiles. ResultsDuring the study period, there were an estimated 81 463 poisoning-related ED visits (351.2 per 100 000 population). Infants, toddlers, youth and those aged 20–64 years had elevated risks of poisoning-related ED visits. Rates were highest among those in neighbourhoods with the greatest material (607.8 per 100 000 population) or social (484.2 per 100 000 population) deprivation. Over time, narcotics and psychodysleptics became increasingly common poisoning agents, while alcohol remained problematic. ConclusionA methodology for estimating ED visit rates in BC was developed and applied to determine poisoning-related ED visit rates among various demographic groups within BC. British Columbians most vulnerable to poisoning have been identified, emphasizing the need for efforts to limit drug overdoses and excessive alcohol intoxication to reduce rates of these preventable injuries.

IntroductionLa crise des opioïdes au Canada a coûté la vie à des milliers de personnes, mettant davantage en lumière que les blessures liées aux intoxications constituent un problème de santé publique important. Cependant, en Colombie-Britannique, où le taux de mortalité par surdose est le plus élevé au Canada, les études n’ont pas encore permis de déterminer quelles populations visitent le plus souvent les urgences pour une intoxication ni quelles substances sont le plus souvent en cause. L’objectif de cette étude était d’explorer ces lacunes après avoir élaboré une méthodologie pour calculer les taux de visite aux urgences en Colombie Britannique. MéthodologieGrâce à une nouvelle méthodologie élaborée dans cette étude, nous avons calculé les taux de visite aux urgences liée à une intoxication sur la période 2012-2013 à 2016-2017 par sexe, groupe d’âge, substance ayant mené à l’intoxication et statut socioéconomique. Les données relatives aux urgences proviennent du Système national d’information sur les soins ambulatoires et les données de population proviennent des profils de recensements de 2016 (ou 2011) de Statistique Canada. RésultatsAu cours de la période étudiée, on estime qu’il y a eu 81 463 visites aux urgences en raison d’une intoxication (351,2 pour 100 000 habitants). Les nourrissons, les tout-petits, les jeunes et les personnes de 20 à 64 ans présentaient un risque élevé de visites aux urgences en raison d’une intoxication. Les taux les plus élevés touchaient les personnes vivant dans les quartiers les plus défavorisés sur le plan matériel (607,8 pour 100 000 habitants) ou social (484,2 pour 100 000 habitants). Au fil du temps, les intoxications causées par les narcotiques et les psychodysleptiques sont devenues de plus en plus fréquentes, l’alcool demeurant toujours un problème. ConclusionNous avons élaboré et appliqué une méthodologie d’estimation des taux de visite aux urgences en Colombie-Britannique pour déterminer ceux liés à une intoxication au sein de divers groupes de population de la province. Maintenant que nous savons quelles populations sont les plus vulnérables aux intoxications en Colombie-Britannique, il faut déployer des efforts pour limiter les surdoses de drogues et les intoxications liées à une consommation excessive d’alcool afin de réduire les taux de ces blessures évitables.

ObjectivesThis study explored how demographic characteristics, life experiences, and firefighting experiences have an impact on work-related injuries among female firefighters, and described events surrounding such work-related injuries.MethodsThis online survey was available from June 2019 to July 2020. Questions related to demographic characteristics, life experiences, firefighting experiences, and work-related injuries. Descriptive analyses characterized variables by the presence or absence of work-related injury, injury severity, job assignment, and country of residence.ResultsThere were 1,160 active female firefighter survey respondents from the US and Canada, 64% of whom reported having at least one work-related injury. US respondents made up 67% of the total but 75% of the injured sample. Injured respondents were older, had been in the fire service longer, and had a greater number of fires and toxic exposures than non-injured respondents. Heavier weight, tobacco use, and alcohol consumption were more common among injured respondents. The two most common contributing factors to work-related injuries were human error and firefighter fatigue. Among respondents who reported an injury-related time loss claim, 69% were wearing protective equipment when injured, and 9% of the injuries directly resulted in new policy implementation.ConclusionsThese findings can help inform resource allocation, and development of new policies and safety protocols, to reduce the number of work-related injuries among female firefighters.

Introduction Evidence suggests the presence of deficiencies in the quality of care provided to up to half of all paediatric trauma patients in Canada, the USA and Australia. Lack of adherence to evidence-based recommendations may be driven by lack of knowledge of clinical practice guidelines (CPGs), heterogeneity in recommendations or concerns about their quality. We aim to systematically review CPG recommendations for paediatric injury care and appraise their quality.Methods and analysis We will identify CPG recommendations through a comprehensive search strategy including Medical Literature Analysis and Retrieval System Online, Excerpta Medica dataBASE, Cochrane library, Web of Science, ClinicalTrials and websites of organisations publishing recommendations on paediatric injury care. We will consider CPGs including at least one recommendation targeting paediatric injury populations on any diagnostic or therapeutic intervention from the acute phase of care with any comparator developed in high-income countries in the last 15 years (January 2007 to a maximum of 6 months prior to submission). Pairs of reviewers will independently screen titles, abstracts and full text of eligible articles, extract data and evaluate the quality of CPGs and their recommendations using Appraisal of Guidelines Research and Evaluation (AGREE) II and AGREE Recommendations Excellence instruments, respectively. We will synthesise evidence on recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence-to-Decision framework and present results within a recommendations matrix.Ethics and dissemination Ethics approval is not a requirement as this study is based on available published data. The results of this systematic review will be published in a peer-reviewed journal, presented at international scientific meetings and distributed to healthcare providers.PROSPERO registration number International Prospective Register of Systematic Reviews (CRD42021226934).

Alzheimer's disease (AD) is the most common form of dementia, which is neuropathologically characterized by extracellular senile plaques containing amyloid-β and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein. Previous studies have suggested a role for septin (SEPTIN) protein family members in AD-associated cellular processes. Here, we elucidated the potential role of presynaptic SEPTIN5 protein and its post-translational modifications in the molecular pathogenesis of AD. RNA and protein levels of SEPTIN5 showed a significant decrease in human temporal cortex in relation to the increasing degree of AD-related neurofibrillary pathology. Conversely, an increase in the phosphorylation of the functionally relevant SEPTIN5 phosphorylation site S327 was observed already in the early phases of AD-related neurofibrillary pathology, but not in the cerebrospinal fluid of individuals fulfilling the criteria for mild cognitive impairment due to AD. According to the mechanistic assessments, a link between SEPTIN5 S327 phosphorylation status and the effects of SEPTIN5 on amyloid precursor protein processing and markers of autophagy was discovered in mouse primary cortical neurons transduced with lentiviral constructs encoding wild type SEPTIN5 or SEPTIN5 phosphomutants (S327A and S327D). C57BL/6 J mice intrahippocampally injected with lentiviral wild type SEPTIN5 or phosphomutant constructs did not show changes in cognitive performance after five to six weeks from the start of injections. However, SEPTIN5 S327 phosphorylation status was linked to changes in short-term synaptic plasticity ex vivo at the CA3-CA1 synapse. Collectively, these data suggest that SEPTIN5 and its S327 phosphorylation status play a pivotal role in several cellular processes relevant for AD.

Background Supracondylar humerus fractures (SCHF) are the most common fractures sustained following a fall onto an outstretched hand among healthy children, and one of the leading causes of hospital admission and surgical intervention. The aim of this study was to examine SCHF occurring at public play spaces—particularly to determine whether or not the playground equipment implicated in injurious falls aligned with Canadian playground safety standards.Methods Cases of children who attended the provincial paediatric orthopaedic clinic following SCHF at a public playground between April 2017 and October 2019 were included in the study. A research assistant visited each playground to measure the play structure type and dimensions, height of the equipment at the point from which the child fell and the type and depth of the surface material, and compare measurements to the 2016 safety standards. Child demographics and injury classification were also noted. Descriptive statistics were calculated and a scatterplot of fall height and surface depth was generated.Results Forty-three sites, representing 47 SCHF cases (18 female, 29 male), were included in the final analysis. Fourteen children sustained type 1 fracture, 23 had type 2 fracture and the remaining 10 had type 3 fracture. Five children with type 2 fracture and all 10 children with type 3 fracture required surgery. The majority of sites had engineered wood fibre surfacing, with surfacing at 35 sites being less than 300 mm deep. Twenty-six play structures were upper body equipment (ie, monkey bars or similar), seven were track rides, five were rotating structures and the rest comprised a variety of classified and unclassified structures. Twenty-seven children fell from a height exceeding 2 m.Conclusions The majority of SCHF cases occurred at playgrounds with insufficient surface depth and/or non-compliant equipment. Upper body equipment, track rides and rotating play structures were of particular concern, as the children fell from heights exceeding the recommended standard, likely reflecting the degradation and compaction of the surfacing material over time.

Abstract Background This study examines social disparities across neighbourhood levels of income, education and employment in relation to overall injury hospital separations in the province of British Columbia, Canada. Further, the study examines the relationships of social disparities to a set of three injury prevention priorities in British Columbia, namely, transport (motor vehicle occupant, pedestrian and cyclist), falls among older adults, and youth self-harm. The goal being to better understand area-based injury incidence with a view to precision prevention initiatives, particularly for more vulnerable populations. Methods Acute hospital separations from the Discharge Abstract Database were identified for all causes of injury and the three BC injury prevention priorities for the period April 1, 2009 to March 31, 2014, inclusive. An ecological approach was applied where each hospital separation case was attributed with the income, education and employment level according to the injured individual’s area of residence, derived from the 2011 CensusPlus data. Results Injury hospital separation data were available for 191 Forward Sortation Areas in BC. Between April 1, 2009 and March 31, 2014, there was a total of 177,861 injury-related hospital separations, averaging 35,572 hospital separations per year and an annual rate of 779 injury hospital separations per 100,000 population. Injury hospital separation rates varied with the measured neighbourhood area socioeconomic status variables. Injury hospital separation rates demonstrated an inverse relationship with neighbourhood levels of income and education. Neighbourhood area socioeconomic status differences were also associated with the injury hospital separation rates for falls among older adults, motor vehicle crashes involving motor vehicle occupants, pedestrians, cyclists and young drivers, and youth self-harm. Conclusions The study results show that neighbourhood levels of income, education and employment are associated with the risk of injury hospital separation. In particular, low education levels in FSAs was associated with increased risk of injury hospital separation, mainly for motor vehicle occupants, pedestrians, young drivers, and youth self-harm. The results of this study provide useful information for implementing injury prevention initiatives and interventions in BC to align with the provincial public health system and road safety strategy goals, particularly for identified priorities.

Abstract Background Active transportation, such as walking and biking, is a healthy way for children to explore their environment and develop independence. However, children can be injured while walking and biking. Many cities make changes to the built environment (e.g., traffic calming features, separated bike lanes) to keep people safe. There is some research on how effective these changes are in preventing adult pedestrians and bicyclists from getting hurt, but very little research has been done to show how safe various environments are for children and youth. Our research program will study how features of the built environment affect whether children travel (e.g., to school) using active modes, and whether certain features increase or decrease their likelihood of injury. Methods First, we will use a cross-sectional study design to estimate associations between objectively measured built environment and objectively measured active transportation to school among child elementary students. We will examine the associations between objectively measured built environment and child and youth pedestrian-motor vehicle collisions (MVCs) and bicyclist-MVCs. We will also use these data to determine the space-time distribution of pedestrian-MVCs and bicyclist-MVCs. Second, we will use a case-crossover design to compare the built environment characteristics of the site where child and youth bicyclists sustain emergency department reported injuries and two randomly selected sites (control sites) along the bicyclist’s route before the injury occurred. Third, to identify implementation strategies for built environment change at the municipal level to encourage active transportation we will conduct: 1) an environmental scan, 2) key informant interviews, 3) focus groups, and 4) a national survey to identify facilitators and barriers for implementing built environment change in municipalities. Finally, we will develop a built environment implementation toolkit to promote active transportation and prevent child pedestrian and bicyclist injuries. Discussion This program of research will identify the built environment associated with active transportation safety and form an evidence base from which municipalities can draw information to support change. Our team’s national scope will be invaluable in providing information regarding the variability in built environment characteristics and is vital to producing evidence-based recommendations that will increase safe active transportation.

No single-omic approach completely elucidates the multitude of alterations taking place in Alzheimer's disease (AD). Here, we coupled transcriptomic and phosphoproteomic approaches to determine the temporal sequence of changes in mRNA, protein, and phosphopeptide expression levels from human temporal cortical samples, with varying degree of AD-related pathology. This approach highlighted fluctuation in synaptic and mitochondrial function as the earliest pathological events in brain samples with AD-related pathology. Subsequently, increased expression of inflammation and extracellular matrix-associated gene products was observed. Interaction network assembly for the associated gene products, emphasized the complex interplay between these processes and the role of addressing post-translational modifications in the identification of key regulators. Additionally, we evaluate the use of decision trees and random forests in identifying potential biomarkers differentiating individuals with different degree of AD-related pathology. This multiomic and temporal sequence-based approach provides a better understanding of the sequence of events leading to AD.

Substantial efforts devoted to decreasing the burden of transport-related injuries (TRIs) in Canada, including public awareness campaigns aiming to influence attitudes and behaviors, may lead the public to perceive other types of injuries differently. This study examined the relationship between public perception of the preventability of injuries and the type of injury (TRIs vs. non-transport unintentional injuries (NTUIs)); and assessed whether exposure to a social marketing campaign (Preventable) influenced this association. A cross-sectional study design employed survey data collected by Preventable between 2015 and 2016 from 1501 British Columbians aged 25–54 years. A multiple linear regression model was applied to examine the relationship between the type of injury (TRIs vs. NTUIs) and attitudes towards preventability, controlling for socio-demographic variables. Exposure to the campaign was tested as an effect modifier. On a scale from 1 to 10, respondents perceived TRIs to be 1.08 points more preventable than NTUIs (95% CI: 1.00 to 1.16, p-value

Introduction: The association between health outcomes and socioeconomic status (SES) has been widely documented, and mortality due to unintentional injuries continues to rank among the leading causes of death among British Columbians. This paper quantified the SES-related disparities in the mortality burden of three British Columbia’s provincial injury prevention priority areas: falls among seniors, transport injury, and youth suicide. Methods: Mortality data (2009 to 2013) from Vital Statistics and dissemination area or local health area level socioeconomic data from CensusPlus 2011 were linked to examine age-standardized mortality rates (ASMRs) and disparities in ASMRs of unintentional injuries and subtypes including falls among seniors (aged 65+) and transport-related injuries as well as the intentional injury type of youth suicide (aged 15 to 24). Disparities by sex and geography were examined, and relative and absolute disparities were calculated between the least and most privileged areas based on income, education, employment, material deprivation, and social deprivation quintiles. Results: Our study highlighted significant sex differences in the mortality burden of falls among seniors, transport injury, and youth suicide with males experiencing significantly higher mortality rates. Notable geographic variations in overall unintentional injury ASMR were also observed across the province. In general, people living in areas with lower income and higher levels of material deprivation had increasingly higher mortality rates compared to their counterparts living in more privileged areas. Conclusion: The significant differences in unintentional and intentional injury-related mortality outcomes between the sexes and by SES present opportunities for targeted prevention strategies that address the disparities.

Objectives An online, evidence-based resource was created to support the development of sport and recreational injury prevention programmes. The resource, called Active & Safe Central (www.activesafe.ca), provides evidence-based information across the public health approach for a number of sport and recreational activities. The objective of this project was to evaluate the perceived usefulness of Active & Safe Central as an educational tool.Design A mixed-methods study design, guided by the RE-AIM (reach, effectiveness, adoption, implementation and maintenance) framework, was used to evaluate Active & Safe Central.Setting Data were collected using an online survey, available to all users of the site, and focus groups (n=2) that took place in Vancouver and Toronto, Canada.Participants Survey respondents (n=87) were recruited online, including parents, coaches, youth and adult athletes, and teachers. Focus group participants (n=16) were key stakeholders and end users, recruited from academia, local health sectors, sport and recreational organisations, and not-for-profit injury prevention organisations.Results Post launch, there were 1712 users visiting the website 2306 times (sessions), with the majority representing new users, over returning users (87.5% and 12.5%, respectively). There were 6340 page visits, with the most popular pages including soccer, playgrounds and ice hockey. Active & Safe Central was reported as a credible source of evidence-based sport and recreational information and that the site would be recommended to others. Information collected from focus group participants was used to inform necessary adaptations to the online platform, including critical navigation issues, visualisations and interactivity. The major themes that emerged from focus group and survey data included increased awareness of injury prevention recommendations and that the recommendations would be used in one’s own sporting activity and/or practice.Conclusions The results of the evaluation suggest the tool is a useful resource for sport and recreational injury information that has significant potential to impact prevention practice.

Introduction. Sachant que l’association entre l'état de santé et le statut socioéconomique (SSE) est largement documentée et que les blessures non intentionnelles continuent de se classer parmi les principales causes de décès chez les Britanno-Colombiens, nous avons voulu quantifier les disparités liées au SSE dans les taux de mortalité associés à trois secteurs prioritaires pour la Colombie-Britannique en matière de prévention des blessures : le suicide chez les jeunes, les blessures liées aux chutes chez les aînés et les blessures liées au transport. Méthodologie. Nous avons jumelé les données liées aux décès (2009 à 2013) tirées des statistiques de l’état civil et des données socioéconomiques de CensusPlus de 2011 à l’échelle de l’aire de diffusion ou de la circonscription sanitaire afin d'étudier les taux de mortalité normalisés selon l’âge (TMNA) et les disparités des TMNA concernant les blessures non intentionnelles et leurs sous-types, notamment les blessures liées aux chutes chez les aînés (65 ans et plus) et les blessures liées au transport, ainsi que le suicide chez les jeunes (15 à 24 ans), ce dernier étant considéré comme une forme de blessure intentionnelle. Nous avons étudié les disparités spatiales et les disparités selon le sexe et nous avons mesuré les disparités relatives et absolues entre les zones moins favorisées et les zones plus favorisées en fonction des quintiles de revenu, de scolarité, d’emploi, de défavorisation matérielle et de défavorisation sociale. Résultats. Notre étude a mis en évidence d’importantes différences entre les sexes en matière de taux de mortalité attribuable au suicide chez les jeunes, à des blessures liées aux chutes chez les aînés et à des blessures liées au transport, les hommes affichant des taux de mortalité beaucoup plus élevés que les femmes. Nous avons également observé des variations spatiales notables dans les TMNA pour l’ensemble des blessures non intentionnelles à l’échelle de la province. En général, la population vivant dans des zones où les revenus étaient faibles et où la défavorisation matérielle était importante a affiché des taux de mortalité plus élevés que la population vivant dans des zones favorisées. Conclusion. Le repérage de différences importantes dans les taux de mortalité liée à des blessures intentionnelles et non intentionnelles entre les sexes et en fonction du SSE ouvre des possibilités quant à l’élaboration de stratégies de prévention ciblées pour réduire ces disparités.

Abstract Background In Canada, road traffic injuries are the leading cause of death among children and youth ≤19. Across the country, there is variability in road traffic injury prevention policies and legislation. Our objective was to compare pediatric road traffic related injury hospitalization and death rates across Canadian provinces. Methods Population-based hospitalization and death rates per 100,000 were analyzed using data from the Discharge Abstract Database and provincial coroner’s reports. Road traffic related injuries sustained by children and youth ≤19 years were analyzed by province and cause between 2006 and 2012. Results The overall transport-related injury morbidity rate for children in Canada was 70.91 per 100,000 population between 2006 and 2012. The Canadian population-based injury hospitalization rates from all transport-related causes significantly decreased from 85.51 to 58.77 per 100,000 (− 4.42; p

Abstract Background It is unclear to what extent pre-clinical studies in genetically homogeneous animal models of amyotrophic lateral sclerosis (ALS), an invariably fatal neurodegenerative disorder, can be informative of human pathology. The disease modifying effects in animal models of most therapeutic compounds have not been reproduced in patients. To advance therapeutics in ALS, we need easily accessible disease biomarkers which can discriminate across the phenotypic variants observed in ALS patients and can bridge animal and human pathology. Peripheral blood mononuclear cells alterations reflect the rate of progression of the disease representing an ideal biological substrate for biomarkers discovery. Methods We have applied TMTcalibrator™, a novel tissue-enhanced bio fluid mass spectrometry technique, to study the plasma proteome in ALS, using peripheral blood mononuclear cells as tissue calibrator. We have tested slow and fast progressing SOD1G93A mouse models of ALS at a pre-symptomatic and symptomatic stage in parallel with fast and slow progressing ALS patients at an early and late stage of the disease. Immunoassays were used to retest the expression of relevant protein candidates. Results The biological features differentiating fast from slow progressing mouse model plasma proteomes were different from those identified in human pathology, with only processes encompassing membrane trafficking with translocation of GLUT4, innate immunity, acute phase response and cytoskeleton organization showing enrichment in both species. Biological processes associated with senescence, RNA processing, cell stress and metabolism, major histocompatibility complex-II linked immune-reactivity and apoptosis (early stage) were enriched specifically in fast progressing ALS patients. Immunodetection confirmed regulation of the immunosenescence markers Galectin-3, Integrin beta 3 and Transforming growth factor beta-1 in plasma from pre-symptomatic and symptomatic transgenic animals while Apolipoprotein E differential plasma expression provided a good separation between fast and slow progressing ALS patients. Conclusions These findings implicate immunosenescence and metabolism as novel targets for biomarkers and therapeutic discovery and suggest immunomodulation as an early intervention. The variance observed in the plasma proteomes may depend on different biological patterns of disease progression in human and animal model.

Protein aggregation in biofluids is a poorly understood phenomenon. Under normal physiological conditions, fluid-borne aggregates may contain plasma or cell proteins prone to aggregation. Recent observations suggest that neurofilaments (Nf), the building blocks of neurons and a biomarker of neurodegeneration, are included in high molecular weight complexes in circulation. The composition of these Nf-containing hetero-aggregates (NCH) may change in systemic or organ-specific pathologies, providing the basis to develop novel disease biomarkers. We have tested ultracentrifugation (UC) and a commercially available protein aggregate binder, Seprion PAD-Beads (SEP), for the enrichment of NCH from plasma of healthy individuals, and then characterised the Nf content of the aggregate fractions using gel electrophoresis and their proteome by mass spectrometry (MS). Western blot analysis of fractions obtained by UC showed that among Nf isoforms, neurofilament heavy chain (NfH) was found within SDS-stable high molecular weight aggregates. Shotgun proteomics of aggregates obtained with both extraction techniques identified mostly cell structural and to a lesser extent extra-cellular matrix proteins, while functional analysis revealed pathways involved in inflammatory response, phagosome and prion-like protein behaviour. UC aggregates were specifically enriched with proteins involved in endocrine, metabolic and cell-signalling regulation. We describe the proteome of neurofilament-containing aggregates isolated from healthy individuals biofluids using different extraction methods.

Introduction: Despite legal protections for young workers in Canada, youth aged 15–24 are at high risk of traumatic occupational injury. While many injury prevention initiatives targeting young workers exist, the challenge faced by youth advocates and employers is deciding what aspect(s) of prevention will be the most effective focus for their efforts. A review of the academic and grey literatures was undertaken to compile the metrics—both the indicators being evaluated and the methods of measurement—commonly used to assess injury prevention programs for young workers. Metrics are standards of measurement through which efficiency, performance, progress, or quality of a plan, process, or product can be assessed. Methods: A PICO framework was used to develop search terms. Medline, PubMed, OVID, EMBASE, CCOHS, PsychINFO, CINAHL, NIOSHTIC, Google Scholar and the grey literature were searched for articles in English, published between 1975-2015. Two independent reviewers screened the resulting list and categorized the metrics in three domains of injury prevention: Education, Environment and Enforcement. Results: Of 174 acquired articles meeting the inclusion criteria, 21 both described and assessed an intervention. Half were educational in nature (N=11). Commonly assessed metrics included: knowledge, perceptions, self-reported behaviours or intentions, hazardous exposures, injury claims, and injury counts. One study outlined a method for developing metrics to predict injury rates. Conclusion: Metrics specific to the evaluation of young worker injury prevention programs are needed, as current metrics are insufficient to predict reduced injuries following program implementation. One study, which the review brought to light, could be an appropriate model for future research to develop valid leading metrics specific to young workers, and then apply these metrics to injury prevention programs for youth.

Abstract Background Children’s risky play is associated with a variety of positive developmental, physical and mental health outcomes, including greater physical activity, self-confidence and risk-management skills. Children’s opportunities for risky play have eroded over time, limited by parents’ fears and beliefs about risk, particularly among mothers. We developed a digital tool and in-person Risk-reframing (RR) workshop to reframe parents’ perceptions of risk and change parenting behaviours. The purpose of this paper is to describe our RR intervention, rationale and protocol for a randomised controlled trial to examine whether it leads to increases in mothers’ tolerance of risk in play and goal attainment relating to promoting their child’s opportunities for risky play. Methods We use a randomised controlled trial design and will recruit a total of 501 mothers of children aged 6–12 years. The RR digital tool is designed for a one-time visit and includes three chapters of self-reflection and experiential learning tasks. The RR in-person tool is a 2-h facilitated workshop in which participants are guided through discussion of the same tasks contained within the digital tool. The control condition consists of reading the Position Statement on Active Outdoor Play. Primary outcome is increased tolerance of risk in play, as measured by the Tolerance of Risk in Play Scale. Secondary outcome is self-reported attainment of a behaviour-change goal that participants set for themselves. We will test the hypothesis that there will be differences between the experimental and control conditions with respect to tolerance of risk in play using mixed-effects models. We will test the hypothesis that there will be differences between the experimental and control conditions with respect to goal attainment using logistic regression. Discussion The results of this trial will have important implications for facilitating the widespread change in parents’ risk perception that is necessary for promoting broad societal understanding of the importance of children’s risky play. In addition, the findings may provide relevant information for the design of behaviour-change tools to increase parental tolerance of risk. Trial registration ClinicalTrials.gov, ID: NCT03374683. Retrospectively registered on 15 December 2017.

Introduction. Malgré la protection juridique dont les jeunes travailleurs au Canada font l’objet, les jeunes de 15 à 24 ans sont exposés à un risque élevé de blessures traumatiques au travail. Étant donné que de nombreuses initiatives de prévention des blessures ciblant les jeunes travailleurs existent, les défenseurs des droits des jeunes et les employeurs doivent relever le défi de choisir quels aspects de la prévention vont être les plus efficaces afin d’y consacrer leurs efforts. Une analyse de la littérature universitaire et de la littérature grise a été entreprise afin de compiler les paramètres (indicateurs évalués et méthodes de mesure) couramment utilisés pour évaluer les programmes de prévention des blessures auprès des jeunes travailleurs. Les paramètres constituent des références de mesure permettant d’évaluer l’efficacité, le rendement, le progrès ou la qualité d’un projet, d’un procédé ou d’un produit. Méthodologie. Nous avons utilisé le modèle PICO pour définir les termes de recherche. Des recherches ont été effectuées dans Medline, PubMed, OVID, EMBASE, CCOHS, PsychINFO, CINAHL, NIOSHTIC, Google Scholar et dans la littérature grise afin de trouver des articles en anglais publiés entre 1975 et 2015. Deux lecteurs critiques indépendants ont examiné la liste des articles et ont classé les paramètres en trois catégories de prévention des blessures : l’éducation, l’environnement et l’application de règlements. Résultats. Sur les 174 articles ayant répondu aux critères d’inclusion, 21 décrivaient et évaluaient une intervention. Parmi ceux-ci, la moitié (n=11) étaient à caractère éducatif. Les paramètres couramment évalués étaient : les connaissances, les perceptions, les comportements ou les intentions autodéclarées, l’exposition aux dangers, les demandes d’indemnisation pour blessures et le taux d’accidents de travail. Une étude présentait une méthode destinée à élaborer des paramètres permettant de prédire les taux de blessure. Conclusion. Des paramètres spécifiques à l’évaluation des programmes de prévention des blessures chez les jeunes travailleurs sont nécessaires, car les paramètres actuels sont insuffisants pour prévoir la diminution du nombre de blessures en lien avec la mise en place de programmes. De notre analyse ressort une étude apte à constituer un modèle pertinent pour les recherches futures visant à élaborer des paramètres de base valides destinés aux jeunes travailleurs, afin de les appliquer ensuite aux programmes de prévention es blessures chez les jeunes.

BackgroundSchool-based injuries represent a sizeable portion of child injuries. This study investigated the rates of school-based injuries in Lebanon, examining injury mechanisms, outcomes and associated risk factors.MethodsData were prospectively collected by intern school nurses at 11 private schools for the 2018-2019 academic year. Descriptive and inferential analyses were performed. Chi-square comparisons were conducted to determine the significance of any differences in injury rates between boys and girls for each category of school.Results4,619 injury cases were collected. The yearly rate for school injuries was 419.1 per 1,000 children for the year 2018-2019. Boys demonstrated a significantly higher injury rate for all mechanisms of injuries, with the exception of being injured while walking, injured in the gym/sports areas, and other areas outside the playground and classroom. Elementary school children had the highest rate of injuries, nearly 2.4 times higher than kindergarten, 2.8 times higher than middle school, and 14.5 times higher than high school. Injuries to the face, upper extremities, and lower extremities were nearly 3 times more common than injuries to other areas of the body. Bumps/hits and bruises were most common-almost 3 times more likely than all other injury types. Injuries were mainly minor or moderate in severity-severe injuries were about 10 times less likely. Most injuries were unintentional, with rates nearly 5 times higher than those with unclear intent and 12 times higher than intentional injuries.ConclusionsSchool injuries represent a relatively common problem. Compliance with playground safety standards coupled with the implementation of injury prevention strategies and active supervision at schools can curtail child injuries and ensure a safe and injury-free school environment.

Methyl-CpG-binding protein 2 (MECP2) is a critical transcriptional regulator for synaptic function. Dysfunction of synapses, as well as microglia-mediated neuroinflammation, represent the earliest pathological events in Alzheimer’s disease (AD). Here, expression, protein levels, and activity-related phosphorylation changes of MECP2 were analyzed in post-mortem human temporal cortex. The effects of wild type and phosphorylation-deficient MECP2 variants at serine 423 (S423) or S80 on microglial and neuronal function were assessed utilizing BV2 microglial monocultures and co-cultures with mouse cortical neurons under inflammatory stress conditions. MECP2 phosphorylation at the functionally relevant S423 site nominally decreased in the early stages of AD-related neurofibrillary pathology in the human temporal cortex. Overexpression of wild type MECP2 enhanced the pro-inflammatory response in BV2 cells upon treatment with lipopolysaccharide (LPS) and interferon-γ (IFNγ) and decreased BV2 cell phagocytic activity. The expression of the phosphorylation-deficient MECP2-S423A variant, but not S80A, further increased the pro-inflammatory response of BV2 cells. In neurons co-cultured with BV2 cells, the MECP2-S423A variant increased the expression of several genes, which are important for the maintenance and protection of neurons and synapses upon inflammatory stress. Collectively, functional analyses in different cellular models suggest that MECP2 may influence the inflammatory response in microglia independently of S423 and S80 phosphorylation, while the S423 phosphorylation might play a role in the activation of neuronal gene expression, which conveys neuroprotection under neuroinflammation-related stress.

OBJECTIVES:Acculturation is a multidimensional process involving changes in behaviour and beliefs. Questionnaires developed to measure acculturation are typically designed for specific ethnic populations and adult experiences. This study developed a questionnaire that measures acculturation among ethnically diverse populations of youth that can be included as a module in population surveys. METHODS:Questionnaires measuring acculturation in youth were identified in the literature. The importance of items from the existing questionnaires was determined using a Delphi process and this informed the development of our questionnaire. The questionnaire was then pilot tested using a sample of 248 Canadians aged 18-25 via an online system. Participants identified as East and South East Asian (27.8%), South Asian (17.7%) and Black (13.7%). The majority were 1st (33.5%) or 2nd generation immigrants (52.0%). After redundant items were eliminated, exploratory factor analysis grouped items into domains, and, for each domain, internal consistency, and convergent validity with immigrant generation then age at immigration estimated. A subset of participants re-completed the questionnaire for reliability estimation. RESULTS:The literature review yielded 117 articles that used 13 questionnaires with a total of 440 questions. The Delphi process reduced these to 32 questions. Pilot testing occurred in 248 Canadians aged 18-25. Following item reduction, 16 questions in three domains remained: dominant culture, heritage language, and heritage culture. All had good internal consistency (Cronbach's alphas > .75). The mean dominant domain score increased with immigrant generation (1st generation: 3.69 (95% CI: 3.49-3.89), 2nd: 4.13 (4.00-4.26), 3rd: 4.40 (4.19-4.61)), and mean heritage language score was higher among those who immigrated after age 12 than before (p = .0001), indicative of convergent validity. CONCLUSIONS:This Bicultural Youth Acculturation Questionnaire has demonstrated validity. It can be incorporated into population health surveys to elucidate the impact of acculturation on health outcomes among bicultural youth.

LC-MS/MS phospho-proteomics is an essential technology to help unravel the complex molecular events that lead to and propagate cancer. We have developed a global phospho-proteomic workflow to determine activity of signaling pathways and drug targets in pancreatic cancer tissue for clinical application.Peptides resulting from tryptic digestion of proteins extracted from frozen tissue of pancreatic ductal adenocarcinoma and background pancreas (n = 12), were labelled with tandem mass tags (TMT 8-plex), separated by strong cation exchange chromatography, then were analysed by LC-MS/MS directly or first enriched for phosphopeptides using IMAC and TiO2, prior to analysis. In-house, commercial and freeware bioinformatic platforms were used to identify relevant biological events from the complex dataset.Of 2,101 proteins identified, 152 demonstrated significant difference in abundance between tumor and non-tumor tissue. They included proteins that are known to be up-regulated in pancreatic cancer (e.g. Mucin-1), but the majority were new candidate markers such as HIPK1 & MLCK. Of the 6,543 unique phosphopeptides identified (6,284 unique phosphorylation sites), 635 showed significant regulation, particularly those from proteins involved in cell migration (Rho guanine nucleotide exchange factors & MRCKα) and formation of focal adhesions. Activator phosphorylation sites on FYN, AKT1, ERK2, HDAC1 and other drug targets were found to be highly modulated (≥2 fold) in different cases highlighting their predictive power.Here we provided critical information enabling us to identify the common and unique molecular events likely contributing to cancer in each case. Such information may be used to help predict more bespoke therapy suitable for an individual case.

Changes in brain amyloid burden have been shown to relate to Alzheimer's disease pathology, and are believed to precede the development of cognitive decline. There is thus a need for inexpensive and non-invasive screening methods that are able to accurately estimate brain amyloid burden as a marker of Alzheimer's disease. One potential method would involve using demographic information and measurements on plasma samples to establish biomarkers of brain amyloid burden; in this study data from the Alzheimer's Disease Neuroimaging Initiative was used to explore this possibility. Sixteen of the analytes on the Rules Based Medicine Human Discovery Multi-Analyte Profile 1.0 panel were found to associate with [(11)C]-PiB PET measurements. Some of these markers of brain amyloid burden were also found to associate with other AD related phenotypes. Thirteen of these markers of brain amyloid burden--c-peptide, fibrinogen, alpha-1-antitrypsin, pancreatic polypeptide, complement C3, vitronectin, cortisol, AXL receptor kinase, interleukin-3, interleukin-13, matrix metalloproteinase-9 total, apolipoprotein E and immunoglobulin E--were used along with co-variates in multiple linear regression, and were shown by cross-validation to explain >30% of the variance of brain amyloid burden. When a threshold was used to classify subjects as PiB positive, the regression model was found to predict actual PiB positive individuals with a sensitivity of 0.918 and a specificity of 0.545. The number of APOE [Symbol: see text] 4 alleles and plasma apolipoprotein E level were found to contribute most to this model, and the relationship between these variables and brain amyloid burden was explored.

Experimental studies in animals suggest that alcohol may influence pathophysiologic response to injury mechanisms. However, biological evidence for the alcohol-injury severity relationship provides conflicting results. The purpose of our retrospective cross-sectional study in 2,323 people was to assess whether blood alcohol level (BAC) adversely influences injury severity in victims of motor vehicle collisions (MVCs). We found no difference in mortality OR 1.09 (0.73–1.62), or length of hospital stay, and a trend for lower ISS score was found in the high-alcohol group (P=0.052). Furthermore, the high-alcohol group demonstrated a lower adjusted rate of severe head injury OR 0.65 (0.48–0.87), chest injury OR 0.58 (0.42–0.80), and serious extremity injury OR 0.10 (0.01–0.76). The findings of our study do not demonstrate a dose-response relationship between alcohol consumption and injury severity in MVCs. This study implies that higher BAC may lead to less severe injuries, without impacting mortality or length of hospital stay, however, further research is required to elucidate the nature of this relationship.