Clinical Practice Guideline Recommendations in Pediatric Mild Traumatic Brain Injury: A Systematic Review.

STUDY OBJECTIVE: Our primary objectives were to identify clinical practice guideline recommendations for children with acute mild traumatic brain injury (mTBI) presenting to an emergency department (ED), appraise their overall quality, and synthesize the quality of evidence and the strength of included recommendations. METHODS: We searched MEDLINE, EMBASE, Cochrane Central, Web of Science, and medical association websites from January 2012 to May 2023 for clinical practice guidelines with at least 1 recommendation targeting pediatric mTBI populations presenting to the ED within 48 hours of injury for any diagnostic or therapeutic intervention in the acute phase of care (ED and inhospital). Pairs of reviewers independently assessed overall clinical practice guideline quality using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool. The quality of evidence on recommendations was synthesized using a matrix based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Evidence-to-Decision framework. RESULTS: We included 11 clinical practice guidelines, of which 6 (55%) were rated high quality. These included 101 recommendations, of which 34 (34%) were based on moderate- to high-quality evidence, covering initial assessment, initial diagnostic imaging, monitoring/observation, therapeutic interventions, discharge advice, follow-up, and patient and family support. We did not identify any evidence-based recommendations in high-quality clinical practice guidelines for repeat imaging, neurosurgical consultation, or hospital admission. Lack of strategies and tools to aid implementation and editorial independence were the most common methodological weaknesses. CONCLUSIONS: We identified 34 recommendations based on moderate- to high-quality evidence that may be considered for implementation in clinical settings. Our review highlights important areas for future research. This review also underlines the importance of providing strategies to facilitate the implementation of clinical practice guideline recommendations for pediatric mTBI.

Children's participatory needs in injury prevention: reflections on supporting children's right to invite and comfort in discussing sensitive topics.

BACKGROUND: Child-centred approaches in injury prevention emphasise the importance of practising bidirectional communications and decentring researcher-child power relations to support children's participation in research. To date, however, a dearth of scholarship offers methodological reflections on how to bolster children's feelings of comfort in discussing sensitive topics such as their injury experiences. GOAL: Drawing from lessons we learnt working with children in a low-income to mid-income neighbourhood in Vancouver, Canada, we discuss the ways in which our strategies to support their participation succeeded in, and at times fell short of, supporting their participatory needs. DISCUSSION: Our discussions focus attention on two important areas for consideration in future injury prevention studies: (1) Children's inclusion in research and the demand for them to share experience and (2) supporting children's right to invite and comfort in discussing sensitive topics such as injury experiences. We discuss the benefits of making research fun for children and being sensitive to their needs at preliminary recruitment and data collection stages. IMPLICATIONS: These discussions can strengthen researchers' work with children by helping them to reflect on strategies that can bolster their desire to participate and feel comfortable sharing perspectives.

Protective Alzheimer's disease-associated APP A673T variant predominantly decreases sAPPß levels in cerebrospinal fluid and 2D/3D cell culture models.

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 (Aß) 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 APPß (sAPPß) and Aß42 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 Aß, 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 sAPPß levels. Concomitantly, the levels of sAPPα were increased, while decreased levels of CTFß and Aß42 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.

TMTpro reagents: a set of isobaric labeling mass tags enables simultaneous proteome-wide measurements across 16 samples.

Isobaric labeling empowers proteome-wide expression measurements simultaneously across multiple samples. Here an expanded set of 16 isobaric reagents based on an isobutyl-proline immonium ion reporter structure (TMTpro) is presented. These reagents have similar characteristics to existing tandem mass tag reagents but with increased fragmentation efficiency and signal. In a proteome-scale example dataset, we compared eight common cell lines with and without Torin1 treatment with three replicates, quantifying more than 8,800 proteins (mean of 7.5 peptides per protein) per replicate with an analysis time of only 1.1 h per proteome. Finally, we modified the thermal stability assay to examine proteome-wide melting shifts after treatment with DMSO, 1 or 20 µM staurosporine with five replicates. This assay identified and dose-stratified staurosporine binding to 228 cellular kinases in just one, 18-h experiment. TMTpro reagents allow complex experimental designs-all with essentially no missing values across the 16 samples and no loss in quantitative integrity.

What children's perspectives on safe and dangerous outdoor play can tell us about their risk-seeking and injury experiences: 'You don't feel right doing the thing that got you hurt'.

BACKGROUND: Unintentional injuries are a leading cause of children's hospitalisations and death globally and are thus a pressing public health concern. Fortunately, they are largely preventable, and understanding children's perspectives on safe and dangerous outdoor play can help educators and researchers identify ways to mitigate the likelihood of their occurrence. Problematically, children's perspectives are rarely included in injury prevention scholarship. In this study, we acknowledge children's right to have their voices heard by exploring the perspectives on safe and dangerous play and injury of 13 children in Metro Vancouver, Canada. METHODS: We employed tenets of risk and sociocultural theory and a child-centred community-based participatory research approach to injury prevention. We conducted unstructured interviews with children aged 9-13 years old. RESULTS: Through our thematic analysis, we identified two themes: (1) 'little' and 'big' injuries and (2) risk and danger. CONCLUSION: Our results suggest children differentiate between 'little' and 'big' injuries by reflecting on the potential loss of opportunities for play with friends. Further, they suggest children avoid play they perceive as dangerous, but enjoy 'risk-seeking' because it is thrilling and provides them with opportunities to push their physical and mental capabilities. Child educators and injury prevention researchers can use our findings to inform their communications with children and make play spaces more accessible to, fun and safe for children.

Blame attribution analysis of police motor vehicle collision reports involving child bicyclists.

BACKGROUND: Injuries resulting from collisions between a bicyclist and driver are preventable and have high economic, personal and societal costs. Studying the language choices used by police officers to describe factors responsible for child bicyclist-motor vehicle collisions may help shift prevention efforts away from vulnerable road users to motorists and the environment. The overall aim was to investigate how police officers attribute blame in child (≤18 years) bicycle-motor vehicle collision scenarios. METHODS: A document analysis approach was used to analyse Alberta Transportation police collision reports from Calgary and Edmonton (2016-2017). Collision reports were categorised by the research team according to perceived blame (child, driver, both, neither, unsure). Content analysis was then used to examine police officer language choices. A narrative thematic analysis of the individual, behavioural, structural and environmental factors leading to collision blame was then conducted. RESULTS: Of 171 police collision reports included, child bicyclists were perceived to be at fault in 78 reports (45.6%) and adult drivers were perceived at fault in 85 reports (49.7%). Child bicyclists were portrayed through language choices as being irresponsible and irrational, leading to interactions with drivers and collisions. Risk perception issues were also mentioned frequently in relation to poor decisions made by child bicyclists. Most police officer reports discussed road user behaviours, and children were frequently blamed for collisions. CONCLUSIONS: This work provides an opportunity to re-examine perceptions of factors related to motor vehicle and child bicyclist collisions with a view to prevention.

Road safety, health equity, and the built environment: perspectives of transport and injury prevention professionals in five Canadian municipalities.

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.

S327 phosphorylation of the presynaptic protein SEPTIN5 increases in the early stages of neurofibrillary pathology and alters the functionality of SEPTIN5.

Alzheimer's disease (AD) is the most common form of dementia, which is neuropathologically characterized by extracellular senile plaques containing amyloid-ß 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.

Alzheimer's genetic risk factor FERMT2 (Kindlin-2) controls axonal growth and synaptic plasticity in an APP-dependent manner.

Although APP metabolism is being intensively investigated, a large fraction of its modulators is yet to be characterized. In this context, we combined two genome-wide high-content screenings to assess the functional impact of miRNAs and genes on APP metabolism and the signaling pathways involved. This approach highlighted the involvement of FERMT2 (or Kindlin-2), a genetic risk factor of Alzheimer's disease (AD), as a potential key modulator of axon guidance, a neuronal process that depends on the regulation of APP metabolism. We found that FERMT2 directly interacts with APP to modulate its metabolism, and that FERMT2 underexpression impacts axonal growth, synaptic connectivity, and long-term potentiation in an APP-dependent manner. Last, the rs7143400-T allele, which is associated with an increased AD risk and localized within the 3'UTR of FERMT2, induced a downregulation of FERMT2 expression through binding of miR-4504 among others. This miRNA is mainly expressed in neurons and significantly overexpressed in AD brains compared to controls. Altogether, our data provide strong evidence for a detrimental effect of FERMT2 underexpression in neurons and insight into how this may influence AD pathogenesis.

Development of a child-centred community-based participatory research approach to injury prevention.

BACKGROUND: Community-based participatory research (CBPR) approaches to injury prevention are conducted so as to foster inclusiveness and collaboration in research processes and settings. Despite the benefits of using CBPR approaches to represent voices in research that are typically marginalised, they are overwhelmingly used in collaborations with youth and adults. Developing a child-centred CBPR approach can serve the important purpose of fostering awareness for children's voices and needs in injury prevention, and can help future researchers engage communities of children in a genuine and respectful way. PURPOSE: To develop a four-staged model of a child-centred CBPR approach to injury prevention and outline the development.

Longitudinal cohort study of injury type, settings, treatment and costs in British Columbia youth, 2003-2013.

BACKGROUND: In 2010 in British Columbia (BC), Canada, total injury costs per capita were higher among youth aged 15-24 years than in any other age group. Injury prevention efforts have targeted injuries with high mortality (transportation injuries) or morbidity (concussions). However, the profile and health costs of common youth injuries (types, locations, treatment choices and prevention strategies) and how these change from adolescence to young adulthood is not known. METHODS: Participants (n=662) were a randomly recruited cohort of BC youth, aged 12-18, in 2003. They were followed biennially across a decade (six assessments). RESULTS: Serious injuries (defined as serious enough to limit normal daily activities) in the last year were reported by 27%-41% of participants at each assessment. Most common injuries were sprains or strains, broken bones, cuts, punctures or animal bites, and severe bruises. Most occurred when playing a sport or from falling. Estimated total direct cost of treatment per injury was approximately $2500. In addition, 25% experienced serious injuries at three or more assessments, indicating possible differences that warrents further investigation. CONCLUSIONS: The occurence and health cost of common injuries to youth and young adults are underestimated in this study but are nevertheless substantial. Ongoing surveillence, awareness raising, and prevention efforts may be needed to reduce these costs.

Risk of non-medical drug overdose following prescription of opioids post-injury: A retrospective cohort study.

Background: There has been increasing scrutiny of opioid prescribing following injury because of concerns that prescribed opioids may contribute to addiction and overdose. This study aimed to better understand the relationship between injury, opioids prescribed before and after injury, and non-medical drug poisoning. Data and methods: Working age (15 to 65 years old) residents of British Columbia's Fraser Health region with an injury that involved an emergency department visit were included. Factors examined included the prescription of opioid and opioid agonist therapy (OAT) medications before and after injury, age, sex, work-related injuries, and socioeconomic status, as well as how they were associated with non-medical drug poisoning risk and post-injury prescriptions. Results: Opioid-naive individuals (those without an opioid prescription captured before their injury) who were prescribed OAT medication-a marker of opioid use disorder-following their injury had a higher risk of subsequent non-medical drug poisoning (Hazard ratio (HR): 21.4 to 22.4 compared with opioid-naive individuals without an opioid or OAT prescription). Post-injury opioid prescription in these individuals increased poisoning risk (HR: 1.27 compared with those without a prescription). Being of male sex (HR: 1.80), being younger (HR: 0.76 for every 10-year increase in age) and living in the lowest-income neighbourhoods (HR: 1.44 compared with the middle quintile) increased poisoning risk. Compared with injuries sustained outside of work, work-related injuries reduced risk (HR: 0.62). Interpretation: Among a cohort of British Columbians visiting emergency departments following an injury, opioid prescribing in patients who were opioid-naive appears to be a minor contributor to non-medical drug poisoning, particularly when compared with other patient factors, such as being male, being younger and having a low socioeconomic status.

TMTpro-18plex: The Expanded and Complete Set of TMTpro Reagents for Sample Multiplexing.

The development of the TMTpro-16plex series expanded the breadth of commercial isobaric tagging reagents by nearly 50% over classic TMT-11plex. In addition to the described 16plex reagents, the proline-based TMTpro molecule can accommodate two additional combinations of heavy carbon and nitrogen isotopes. Here, we introduce the final two labeling reagents, TMTpro-134C and TMTpro-135N, which permit the simultaneous global protein profiling of 18 samples with essentially no missing values. For example, six conditions with three biological replicates can now be perfectly accommodated. We showcase the 18plex reagent set by profiling the proteome and phosphoproteome of a pair of isogenic mammary epithelial cell lines under three conditions in triplicate. We compare the depth and quantitative performance of this data set with a TMTpro-16plex experiment in which two samples were omitted. Our analysis revealed similar numbers of quantified peptides and proteins, with high quantitative correlation. We interrogated further the TMTpro-18plex data set by highlighting changes in protein abundance profiles under different conditions in the isogenic cell lines. We conclude that TMTpro-18plex further expands the sample multiplexing landscape, allowing for complex and innovative experimental designs.

History of injury in a developing country: a scoping review of injury literature in Lebanon.

BACKGROUND: Lebanon, an Eastern Mediterranean country, suffers a large burden of injury as a consequence of conflict and war, political instability, and the lack of policies and safety regulations. This article aims to systematically map and comprehensively describe the injury research literature in Lebanon and, to identify gaps for future research. METHODS: MEDLINE, Embase, Eric and SafetyLit, and the grey literature, including conference proceedings, theses and dissertations, government and media reports, were searched without any date or language limits. Data were extracted from 467 documents using REDCap. RESULTS: War-related injuries were the most prevalent type of injury in Lebanon, followed by homicide and other forms of violence. While existing literature targeted vulnerable and at-risk populations, the vast majority focused solely on reporting the prevalence of injuries and associated risk factors. There are considerable gaps in the literature dealing with the integration of preventive programs and interventions across all populations. CONCLUSIONS: Lebanon, historically and currently, experiences a high number of injuries from many different external causes. To date, efforts have focused on reporting the prevalence of injuries and making recommendations, rather than implementing and evaluating interventions and programs to inform policies. Future injury related work should prioritize interventions and prevention programs.

A Web-Based and In-Person Risk Reframing Intervention to Influence Mothers' Tolerance for, and Parenting Practices Associated With, Children's Outdoor Risky Play: Randomized Controlled Trial.

BACKGROUND: Outdoor risky play, such as climbing, racing, and independent exploration, is an important part of childhood and is associated with various positive physical, mental, and developmental outcomes for children. Parental attitudes and fears, particularly mothers', are a major deterrent to children's opportunities for outdoor risky play. OBJECTIVE: The aim of this study was to evaluate the efficacy of 2 versions of an intervention to reframe mothers' perceptions of risk and change parenting behaviors: a web-based intervention or an in-person workshop, compared with the control condition. METHODS: The Go Play Outside! randomized controlled trial was conducted in Canada from 2017 to 2018. Participants were recruited through social media, snowball sampling, and community notices. Mothers of children aged 6-12 years were self-assessed through eligibility questions, and those eligible and consented to participate in the study were randomized into a fully automated web-based intervention, the in-person workshop, or the control condition. The intervention was underpinned by social cognitive theory, incorporating behavior change techniques. Participants progressed through a series of self-reflection exercises and developed a goal for change. Control participants received the Position Statement on Active Outdoor Play. The primary outcome was increase in tolerance of risky play and the secondary outcome was goal attainment. Data were collected online via REDCap at baseline, 1 week, and 3 months after the intervention. Randomization was conducted using sealed envelope. Allocations were concealed to researchers at assignment and data analysis. We conducted mediation analyses to examine whether the intervention influenced elements of social cognitive theory, as hypothesized. RESULTS: A total of 451 mothers were randomized and completed baseline sociodemographic assessments: 150 in the web-based intervention, 153 in the in-person workshop, and 148 in the control condition. Among these, a total of 351 mothers completed the intervention. At 1 week after the intervention, 113, 85, and 135 mothers completed assessments for each condition, respectively, and at 3 months after the intervention, 105, 84, and 123 completed the assessments, respectively. Compared with mothers in the control condition, mothers in the web-based intervention had significantly higher tolerance of risky play at 1 week (P=.004) and 3 months after the intervention (P=.007); and mothers in the in-person workshop had significantly higher tolerance of risky play at 1 week after the intervention (P=.02). No other significant outcomes were found. None of the potential mediators were found to significantly mediate the outcomes. CONCLUSIONS: The trial demonstrates that the web-based intervention was effective in increasing mothers' tolerance for risk in play. TRIAL REGISTRATION: ClinicalTrials.gov NCT03374683; https://clinicaltrials.gov/ct2/show/NCT03374683. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-018-2552-4.

Preclinical and clinical biomarker studies of CT1812: A novel approach to Alzheimer's disease modification.

INTRODUCTION: Amyloid beta (Aß) oligomers are one of the most toxic structural forms of the Aß protein and are hypothesized to cause synaptotoxicity and memory failure as they build up in Alzheimer's disease (AD) patients' brain tissue. We previously demonstrated that antagonists of the sigma-2 receptor complex effectively block Aß oligomer toxicity. CT1812 is an orally bioavailable, brain penetrant small molecule antagonist of the sigma-2 receptor complex that appears safe and well tolerated in healthy elderly volunteers. We tested CT1812's effect on Aß oligomer pathobiology in preclinical AD models and evaluated CT1812's impact on cerebrospinal fluid (CSF) protein biomarkers in mild to moderate AD patients in a clinical trial (ClinicalTrials.gov NCT02907567). METHODS: Experiments were performed to measure the impact of CT1812 versus vehicle on Aß oligomer binding to synapses in vitro, to human AD patient post mortem brain tissue ex vivo, and in living APPSwe /PS1dE9 transgenic mice in vivo. Additional experiments were performed to measure the impact of CT1812 versus vehicle on Aß oligomer-induced deficits in membrane trafficking rate, synapse number, and protein expression in mature hippocampal/cortical neurons in vitro. The impact of CT1812 on cognitive function was measured in transgenic Thy1 huAPPSwe/Lnd+ and wild-type littermates. A multicenter, double-blind, placebo-controlled parallel group trial was performed to evaluate the safety, tolerability, and impact on protein biomarker expression of CT1812 or placebo given once daily for 28 days to AD patients (Mini-Mental State Examination 18-26). CSF protein expression was measured by liquid chromatography with tandem mass spectrometry or enzyme-linked immunosorbent assay in samples drawn prior to dosing (Day 0) and at end of dosing (Day 28) and compared within each patient and between pooled treated versus placebo-treated dosing groups. RESULTS: CT1812 significantly and dose-dependently displaced Aß oligomers bound to synaptic receptors in three independent preclinical models of AD, facilitated oligomer clearance into the CSF, increased synaptic number and protein expression in neurons, and improved cognitive performance in transgenic mice. CT1812 significantly increased CSF concentrations of Aß oligomers in AD patient CSF, reduced concentrations of synaptic proteins and phosphorylated tau fragments, and reversed expression of many AD-related proteins dysregulated in CSF. DISCUSSION: These preclinical studies demonstrate the novel disease-modifying mechanism of action of CT1812 against AD and Aß oligomers. The clinical results are consistent with preclinical data and provide evidence of target engagement and impact on fundamental disease-related signaling pathways in AD patients, supporting further development of CT1812.

Lowering Sample Requirements to Study Tyrosine Kinase Signaling Using Phosphoproteomics with the TMT Calibrator Approach.

Analysis of tyrosine kinase signaling is critical for the development of targeted cancer therapy. Currently, immunoprecipitation of phosphotyrosine (pY) peptides prior to liquid chromatography-tandem mass spectrometry (LC-MS/MS) is used to profile tyrosine kinase substrates. A typical protocol requests 10 mg of total protein from ≈108 cells or 50-100 mg of tissue. Large sample requirements can be cost prohibitive or not feasible for certain experiments. Sample multiplexing using chemical labeling reduces the protein amount required for each sample, and newer approaches use a material-rich reference channel as a calibrator to trigger detection and quantification for smaller samples. Here, it is demonstrated that the tandem mass tag (TMT) calibrator approach reduces the sample input for pY profiling tenfold (to ≈1 mg total protein per sample from 107 cells grown in one plate), while maintaining the depth of pY proteome sampling and the biological content of the experiment. Data are available through PRIDE (PXD019764 for label-free and PXD018952 for TMT). This strategy opens more opportunities for pY profiling of large sample cohorts and samples with limited protein quantity such as immune cells, xenograft models, and human tumors.

Fall-related deaths among older adults in British Columbia: cause and effect of policy change.

BACKGROUND: The British Columbia Coroners Service implemented a policy in 2010 advising the reclassification of underlying causes of deaths due to falls from 'natural' to 'accidental'. This study investigates whether observed data trends reflect this change in practice, are artefacts of inconsistent reporting, or indicate a true increase in fall-related deaths. METHODS: Mortality data were analysed from 2004 to 2017 for cases with International Statistical Classification of Diseases and Related Health Problems, 10th Revision fall codes W00-W19, occurring among adults aged 60 years and older. RESULTS: From 2010 to 2012, accidental fall-related deaths increased among those aged 80 years and older, followed by an increase in natural deaths with fall as the contributing cause. CONCLUSIONS: Changes in reporting resulting from the 2010 policy change were observed; however, post-2012 data indicate a reversion to previous reporting practices.

E-cigarettes: A new hazard for children and adolescents.

OBJECTIVES: Electronic cigarettes and fluid (e-cigarettes, e-fluid) are hazardous materials that when inhaled or ingested may pose significant health risks to children and adolescents. The objective of this work was to explore the spectrum of injury related to e-cigarette exposure among Canadian children and adolescents. METHODS: A one-time survey was sent to all paediatricians in Canada. Information was collected on children and adolescents who presented with e-cigarette exposure (inhalation and ingestion cases) in the previous 12 months. Questions included the number of injuries and symptoms, in addition to age, sex, treatment setting, intentional e-cigarette use, and how the products were accessed. RESULTS: A total of 520 surveys were completed and returned, identifying 35 cases. Symptoms related to inhalation were present in 30 cases and in 5 ingestion cases (5 unintentional, 0 intentional). For inhalation cases, most were male, ages 15 to 19 years, who sought treatment for nausea/vomiting, cough, throat irritation, or acute nicotine toxicity in an outpatient clinic/office. Most inhalation cases reported e-cigarette use 2 to 3 days/week, and e-cigarettes purchases from a mall kiosk/store. For ingestion cases, most were male, ages 1 to 4 years presenting to an emergency department with nausea/vomiting, cough, or respiratory irritation. Younger cases accessed e-fluid at home, older cases purchased in a mall kiosk/store. E-fluid flavours reported consumed were fruit, candy, and tobacco. CONCLUSIONS: E-cigarettes, recently introduced into the North American market are hazardous to children and adolescents. Given the low response rate to the survey, further investigation into the true burden of injury, as well as the risks that e-cigarettes pose, together with ways to reduce exposure, is needed.

A multiomic approach to characterize the temporal sequence in Alzheimer's disease-related pathology.

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.