Identification of an FMNL2 Interactome by Quantitative Mass Spectrometry.

Formin Homology Proteins (Formins) are a highly conserved family of cytoskeletal regulatory proteins that participate in a diverse range of cellular processes. FMNL2 is a member of the Diaphanous-Related Formin sub-group, and previous reports suggest FMNL2's role in filopodia assembly, force generation at lamellipodia, subcellular trafficking, cell-cell junction assembly, and focal adhesion formation. How FMNL2 is recruited to these sites of action is not well understood. To shed light on how FMNL2 activity is partitioned between subcellular locations, we used biotin proximity labeling and proteomic analysis to identify an FMNL2 interactome. The interactome identified known and new FMNL2 interacting proteins with functions related to previously described FMNL2 activities. In addition, our interactome predicts a novel connection between FMNL2 and extracellular vesicle assembly. We show directly that FMNL2 protein is present in exosomes.

Sleep and insulin sensitivity in adolescents at risk of type 2 diabetes: the Sleep Manipulation in Adolescents at Risk of Type 2 Diabetes (SMART2D)randomized crossover study.

STUDY OBJECTIVES: To investigate the effect of increasing sleep duration for 1 week, compared to a week of habitual and decreased sleep, on insulin sensitivity(IS) in adolescents at risk for type 2 diabetes(T2D). METHODS: Adolescents, 13-18y old, at risk for T2D, with obesity and other risk factors, were recruited for a randomized(1:1), open-label, sex-stratified crossover study, that manipulated time-in-bed to modify sleep duration (measured by actigraphy). Following a week of habitual(HB) sleep, time-in-bed was increased(IN) and decreased(DE) by 1h30min/night for 1 week, counterbalanced across participants(HBINDE or HBDEIN), and separated by a week of washout sleep. The main outcome measure was IS, obtained via 2-h oral-glucose-tolerance-test conducted after each sleep week. RESULTS: Of the 43 participants recruited, 36(84%) completed all sleep interventions (52.8% female, age=15.1y, body-mass-index=99.9th percentile, order: HBINDE=18 and HBDEIN=18). On average, during the HB week, participants slept 7h31min/night; sleep duration was 1h02min/night higher during the IN week and 1h19min/night lower during the DE week. We found a significant effect of sleep week on IS with a large effect size. Following the IN sleep week, IS was 20% higher compared to after the HB and DE sleep weeks, but there was no significant difference in IS following HB versus DE sleep weeks. CONCLUSION: Whenever possible, clinicians should empower youth at risk of T2D to improve their sleep duration, since even a modest increase in sleep duration of 1h/night for one-week can have a positive impact on IS in this population.

Sleep timing and health indicators in children and adolescents: a systematic review. / Horaire de sommeil et indicateurs de santé chez les enfants et les adolescents : revue systématique.

INTRODUCTION: To continue to inform sleep health guidelines and the development of evidence-based healthy sleep interventions for children and adolescents, it is important to better understand the associations between sleep timing (bedtime, wake-up time, midpoint of sleep) and various health indicators. The objective of this systematic review was to examine the associations between sleep timing and 9 health indicators in apparently healthy children and adolescents 5 to 18 years old. METHODS: Studies published in the 10 years preceding January 2021 were identified from searches in four electronic databases. This systematic review followed the guidelines prescribed in PRISMA 2020, the methodological quality and risk of bias were scored, and the summary of results used a best-evidence approach for accurate and reliable reporting. RESULTS: Forty-six observational studies from 21 countries with 208 992 unique participants were included. Sleep timing was assessed objectively using actigraphy in 24 studies and subjectively in 22 studies. The lack of studies in some of the health outcomes and heterogeneity in others necessitated using a narrative synthesis rather than a metaanalysis. Findings suggest that later sleep timing is associated with poorer emotional regulation, lower cognitive function/academic achievement, shorter sleep duration/ poorer sleep quality, poorer eating behaviours, lower physical activity levels and more sedentary behaviours, but few studies demonstrated associations between sleep timing and adiposity, quality of life/well-being, accidents/injuries, and biomarkers of cardiometabolic risk. The quality of evidence was rated as "very low" across health outcomes using GRADE. CONCLUSION: The available evidence, which relies on cross-sectional findings, suggests that earlier sleep timing is beneficial for the health of school-aged children and adolescents. Longitudinal studies and randomized controlled trials are needed to better advance this field of research. (PROSPERO registration no.: CRD42020173585).

Impact of a geriatric consultation service on outcomes in older trauma patients: a before-after study.

PURPOSE: Early geriatric involvement is recommended for older trauma patients. We wished to determine the impact of geriatric consultation on mortality, hospital length of stay and discharge disposition in older patients who were admitted to our Level 1 trauma unit. METHODS: We completed a health records review of trauma unit patients, age ≥ 75 years old with Injury Severity Score (ISS) ≥ 12, before (11/2015-10/2017) and after (11/2017-10/2019) implementation of a geriatric trauma consultation initiative. Primary outcomes were mortality, hospital length of stay and discharge destination. Secondary objectives were adherence to the geriatric trauma consult process and identification of geriatric-specific issues. A multivariable analysis controlling for age, gender, multi-morbidity and ISS was undertaken. RESULTS: 157 patients pre-implementation and 172 post-implementation with mean age 83.8 years and 53.8% females were included. Geriatric consultation had no impact on in-hospital mortality [OR 0.70 (95% CI 0.31-1.58)] or length of stay [ß 0.68 (95%CI - 1.35-2.72)]. Patients who received a geriatric consultation were more likely to be discharged home (OR 2.01 (95% CI 1.24-3.24). The adherence to consultation process was 99.4%. Mobility, pain and cognitive impairment were the most common geriatric concerns, identified in 76.6, 61.1 and 50.0% of older trauma patients, respectively. CONCLUSION: Older trauma patients that receive geriatric trauma consultation are more likely to be discharged home. Collaboration between trauma and geriatric specialists is beneficial and may lead to meaningful improvements in outcomes for older trauma patients.

Integrating sex and gender in studies of cardiac resynchronization therapy: a systematic review.

AIMS: To examine the prevalence, temporal changes, and impact of the National Institute of Health (NIH) Sex as a Biological Variable (SABV) policy on sex and gender reporting and analysis in cardiac resynchronization therapy (CRT) cohort studies. METHODS AND RESULTS: We searched MEDLINE, EMBASE, and Web of Science for cohort studies reporting the effectiveness and safety of CRT in heart failure patients from January 2000 to June 2020, with no language restrictions. Segmented regression analysis was used for policy analysis. We included 253 studies. Fourteen per cent considered sex in the study design. Outcome data disaggregated by sex were only reported in 17% of the studies. Of the studies with statistical models (n = 173), 57% were adjusted for sex. Sixty-eight per cent of those reported an effect size for sex on the outcome. Sex-stratified analyses were conducted in 13% of the studies. Temporal analysis shows an increase in sex reporting in background, statistical models, study design, and discussion. Besides statistical models, NIH SABV policy analysis showed no significant change in the reporting of sex in study sections. Gender was not reported or analysed in any study. CONCLUSIONS: There is a need to improve the study design, analysis, and completeness of reporting of sex in CRT cohort studies. Inadequate sex integration in study design and analysis may potentially hinder progress in understanding sex disparities in CRT. Deficiencies in the integration of sex in studies could be overcome by implementing guidance that already exists.

Physical distancing messages targeting youth on the social media accounts of Canadian public health entities and the use of behavioral change techniques.

INTRODUCTION: Physical distancing (PD) is an important public health strategy to reduce the transmission of COVID-19 and has been promoted by public health authorities through social media. Although youth have a tendency to engage in high-risk behaviors that could facilitate COVID-19 transmission, there is limited research on the characteristics of PD messaging targeting this population on social media platforms with which youth frequently engage. This study examined social media posts created by Canadian public health entities (PHEs) with PD messaging aimed at youth and young adults aged 16-29 years and reported behavioral change techniques (BCTs) used in these posts. METHODS: A content analysis of all social media posts of Canadian PHEs from Facebook, Twitter, Instagram and YouTube were conducted from April 1st to May 31st, 2020. Posts were classified as either implicitly or explicitly targeting youth and young adults. BCTs in social media posts were identified and classified based on Behavior Change Technique Taxonomy version 1 (BCTTv1). Frequency counts and proportions were used to describe the data. RESULTS: In total, 319 youth-targeted PD posts were identified. Over 43% of the posts originated from Ontario Regional public health units, and 36.4 and 32.6% of them were extracted from Twitter and Facebook, respectively. Only 5.3% of the total posts explicitly targeted youth. Explicit posts were most frequent from federal PHEs and posted on YouTube. Implicit posts elicited more interactions than explicit posts regardless of jurisdiction level or social media format. Three-quarters of the posts contained at least one BCT, with a greater portion of BCTs found within implicit posts (75%) than explicit posts (52.9%). The most common BCTs from explicit posts were instructions on how to perform a behavior (25.0%) and restructuring the social environment (18.8%). CONCLUSIONS: There is a need for more PD messaging that explicitly targets youth. BCTs should be used when designing posts to deliver public health messages and social media platforms should be selected depending on the target population.

Sex differences in CRT device implantation rates, efficacy, and complications following implantation: protocol for a systematic review and meta-analysis of cohort studies.

INTRODUCTION: There is abundant evidence for sex differences in the diagnosis, implantation, and outcomes for cardiac resynchronization therapy (CRT) devices. Controversial data suggesting women are less likely to receive the device regardless of the greater benefit. The aim of this review is to assess sex differences in the implantation rate, clinical effectiveness, and safety of patients receiving CRT devices. METHODS: We will conduct a systematic literature search of MEDLINE, Embase, and Web of Science to identify cohort studies that meet our eligibility criteria. Title and full text screening will be conducted in duplicate independently. Eligible studies report clinical effectiveness or safety of patients receiving CRT device while providing sex-disaggregated data. Implantation rate will be extracted from the baseline characteristics tables of the studies. The effectiveness outcomes include the following: all-cause death, hospitalization, peak oxygen consumption (pVO2), quality of life (QoL), 6-min walk test, NYHA class reduction, LVEF, and heart failure hospitalization. The complication outcomes include the following: contrast-induced nephropathy, pneumothorax, pocket-related hematoma, pericardial tamponade, phrenic nerve stimulation, device infection, death, pulmonary edema, electrical storm, cardiogenic shock, and hypotension requiring resuscitation. Description of included studies will be reported in detail and outcomes will be meta-analyzed and presented using forest plots when feasible. Risk of bias will be assessed using the Newcastle-Ottawa Scale (NOS) by two review authors independently. GRADE approach will be used to assess the certainty of evidence. DISCUSSION: The aim of this review is to determine the presence of differences in CRT implantation between women and men as well as differences in clinical effectiveness and safety of CRT after device implantation. Results from this systematic review will provide important insights into sex differences in CRT devices that could contribute to the development of sex-specific recommendations and inform policy. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020204804.

Combinations of physical activity, sedentary time, and sleep duration and their associations with depressive symptoms and other mental health problems in children and adolescents: a systematic review.

BACKGROUND: For optimal health benefits, the Canadian 24-Hour Movement Guidelines for Children and Youth (aged 5-17 years) recommend an achievement of high levels of physical activity (≥60 min of moderate-to-vigorous physical activity), low levels of sedentary behaviour (≤2 h of recreational screen time), and sufficient sleep (9-11 h for children or 8-10 h for adolescents) each day. The objective of this systematic review was to examine how combinations of physical activity, sedentary time, and sleep duration relate to depressive symptoms and other mental health indicators among children and adolescents. METHODS: Literature was obtained through searching Medline, EMBASE, PsycINFO, and SportDiscus up to September 30, 2019. Peer-reviewed studies published in English or French were included if they met the following criteria: population (apparently healthy children and adolescents with a mean age of 5-17 years), intervention/exposure (combinations of physical activity, sedentary time, and sleep duration), and outcomes (depressive symptoms and other mental health indicators). A risk of bias assessment was completed for all included studies using the methods described in the Cochrane Handbook. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to assess the quality of evidence for each health indicator. Narrative syntheses were employed to describe the results due to high levels of heterogeneity across studies. RESULTS: A total of 13 cross-sectional studies comprised in 10 papers met inclusion criteria. Data across studies involved 115,540 children and adolescents from 12 countries. Overall, the findings indicated favourable associations between meeting all 3 recommendations and better mental health indicators among children and adolescents when compared with meeting none of the recommendations. There was evidence of a dose-response gradient between an increasing number of recommendations met and better mental health indicators. Meeting the screen time and sleep duration recommendations appeared to be associated with more mental health benefits than meeting the physical activity recommendation. The quality of evidence reviewed was "very low" according to GRADE. CONCLUSIONS: The findings indicate favourable associations between meeting all 3 movement behaviour recommendations in the 24-h guidelines and better mental health indicators among children and adolescents. There is a clear need for high-quality studies that use robust measures of all movement behaviours and validated measures of mental health to increase our understanding in this topic area.