The role of individual subunits in the targeting and function of the mammalian BRG1-associated factors (BAF) complex in embryonic stem cell (ESC) pluripotency maintenance has not yet been elucidated. ...Here we find that the Bromodomain containing protein 9 (BRD9) and Glioma tumor suppressor candidate region gene 1 (GLTSCR1) or its paralog GLTSCR1-like (GLTSCR1L) define a smaller, non-canonical BAF complex (GBAF complex) in mouse ESCs that is distinct from the canonical ESC BAF complex (esBAF). GBAF and esBAF complexes are targeted to different genomic features, with GBAF co-localizing with key regulators of naive pluripotency, which is consistent with its specific function in maintaining naive pluripotency gene expression. BRD9 interacts with BRD4 in a bromodomain-dependent fashion, which leads to the recruitment of GBAF complexes to chromatin, explaining the functional similarity between these epigenetic regulators. Together, our results highlight the biological importance of BAF complex heterogeneity in maintaining the transcriptional network of pluripotency.
In this single-arm non-comparative trial, 13 patients in an Australian hospital with severe Staphylococcus aureus infections were intravenously administered a good manufacturing practice-quality ...preparation of three Myoviridae bacteriophages (AB-SA01) as adjunctive therapy. AB-SA01 was intravenously administered twice daily for 14 d and the clinical, haematological and blood biochemical parameters of the recipients were monitored for 90 d. The primary outcome was the assessment of safety and tolerability (that is, pain and redness at the infusion site and systemic adverse reactions, such as fever, tachycardia, hypotension, diarrhoea or abdominal pain and the development of renal or hepatic dysfunction). No adverse reactions were reported, and our data indicate that AB-SA01 administered in this way is safe in severe S. aureus infections, including infective endocarditis and septic shock. Future controlled trials will be needed to determine the efficacy of AB-SA01 but no phage resistance evolved in vivo and the measurements of bacterial and phage kinetics in blood samples suggest that 12 h dosing of 10
plaque-forming units may be a rational basis for further studies.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The information provided by the scientific studies and control measures implemented in the Pearl River Delta (PRD) region of China reveals that tremendous progress has been made in the understanding ...of regional air pollution issues and the deployment of mitigation measures for alleviating these problems. Given the unparalleled rapid economic growth in the PRD over the past two decades, such progress was only made possible by strong, science-based support and the partnerships between government and research institutions in the region and overseas. Researchers from these partnership programs and related studies have deployed cutting-edge expertise and experience in various crucial mainland China and mainland China/Hong Kong-level projects. China recognizes the importance of protecting the environment and cleaning up the air in the pursuit of sustainable growth and economic development. To avoid falling into a cycle of event-driven clean-up efforts, China has recently taken a major step and updated the national ambient air quality standards. Clearly, China is implementing an increasing number of evidence-based policies to address air pollution problems. Thus, to bring a fresh impetus at a national level, the PRD must maintain and augment the Hong Kong-mainland collaborative momentum, inducing a “whole-China” effort to clean up air pollution. To strengthen the science-based support system and ensure continuous and concerted effort in implementing the regional multi-pollutant control strategy, there must be an overarching and integral Hong Kong–Guangdong science consortium framework supporting the formulation of regional policy and control measures built on common goals under the “one country, two systems” principle. The “PRD Approach” of the air quality management regime reflected regional cooperative efforts in synchronous air pollutant control, catalyzed the crucial role of information disclosure and subtly transformed the air quality management approach to overcome the nation's new air pollution challenges.
•The “PRD approach” air quality management is emerged to tackle regional air pollution.•Its evidence-based approach brings fresh impetus to traditional command-control.•The PRD experiences also exert “whole China” influence and other developing areas.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
•Guidelines recommend decreasing total daily dose when switching from insulin injections to pump.•Decreases in TDD can depend on: age/puberty, diabetes control, hypoglycemia and insulin ...regimen.•Changes in TDD when switching from injections to insulin pump should be individualized.
To assess change in total daily dose (TDD) of insulin following a switch from subcutaneous (SC) injections to continuous subcutaneous insulin infusion (CSII) in pediatric patients with type 1 diabetes (T1D). Secondary objectives were to determine the change in %basal insulin, insulin to carbohydrate (I:C) ratios, insulin sensitivity factor (ISF), and HbA1c/IDAA1c.
A retrospective chart review of patients < 18 years of age who transitioned from SC to CSII at the Alberta Children’s Hospital (Calgary, Alberta, Canada) between January 2019 and March 2022.
There was an increase of 0.04 units/kg/day in TDD from baseline vs 1–3 months later (p = 0.04, 95 % confidence interval (CI) 0.002, 0.072). When stratified by age, a similar increase in TDD was observed in age 5–12 years only (p = 0.05, 95 % CI 0.0006, 0.8236). There was a decrease in overall %basal insulin by 3 (44 % of TDD at baseline vs 41 % of TDD on CSII). (p = 0.02, 95 % CI −5.5, −0.4). No strengthening was seen in I:C ratios from baseline vs 1–3 months later. There was a significant strengthening of I:C ratios at all meals in the basal bolus group from 1–3 weeks to 1–3 months post-CSII; overall strengthening of ISF at both time points; and an overall HbA1c decrease −0.30 (p < 0.0001, CI −0.45, −0.15). Each extra year with diabetes was associated with a decrease in HbA1c by 0.07 % (p = 0.006).
TDD of insulin was not found to be decreased post CSII initiation and patient characteristics should be considered when changing from SC to CSII. HbA1c was significantly improved post CSII.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Ambient air measurements of volatile organic compounds (VOCs) and oxygenated volatile organic compounds (OVOCs) were conducted and characterised during a two-year grid study in the Pearl River Delta ...(PRD) region of southern China. The present grid study pioneered the systematic investigation of the nature and characteristics of complex VOC and OVOC sources at a regional scale. The largest contributing VOCs, accounting over 80% of the total VOCs mixing ratio, were toluene, ethane, ethyne, propane, ethene, butane, benzene, pentane, ethylbenzene, and xylenes. Sub-regional VOC spatial characteristics were identified, namely: i) relatively fresh pollutants, consistent with elevated vehicular and industrial activities, around the PRD estuary; and ii) a concentration gradient with higher mixing ratios of VOCs in the west as compared with the eastern part of PRD. Based on alkyl nitrate aging determination, a high hydroxyl radical (OH) concentration favoured fast hydrocarbon reactions and formation of locally produced ozone. The photochemical reactivity analysis showed aromatic hydrocarbons and alkenes together consisted of around 80% of the ozone formation potential (OFP) among the key VOCs. We also found that the OFP from OVOCs should not be neglected since their OFP contribution was more than one-third of that from VOCs alone. These findings support the choice of current air pollution control policy which focuses on vehicular sources but warrants further controls. Industrial emissions and VOCs emitted by solvents should be the next targets for ground-level ozone abatement.
► The first and foremost large spatial–temporal VOCs grid study in the PRD region. ► More detailed VOCs spatial emission characteristics were identified. ► High OH concentration in PRD favoured fast reactions and ozone formation. ► Ozone formation potential of VOCs and OVOCs were analysed. ► Findings supported further control measures and policies formulation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Despite the growing number of mobile health (mHealth) interventions targeting childhood obesity, few studies have characterized user typologies derived from individuals' patterns of interactions with ...specific app features (digital phenotypes).
This study aims to identify digital phenotypes among 214 parent-child dyads who used the Aim2Be mHealth app as part of a randomized controlled trial conducted between 2019 and 2020, and explores whether participants' characteristics and health outcomes differed across phenotypes.
Latent class analysis was used to identify distinct parent and child phenotypes based on their use of the app's behavioral, gamified, and social features over 3 months. Multinomial logistic regression models were used to assess whether the phenotypes differed by demographic characteristics. Covariate-adjusted mixed-effect models evaluated changes in BMI z scores (zBMI), diet, physical activity, and screen time across phenotypes.
Among parents, 5 digital phenotypes were identified: socially engaged (35/214, 16.3%), independently engaged (18/214, 8.4%) (socially and independently engaged parents are those who used mainly the social or the behavioral features of the app, respectively), fully engaged (26/214, 12.1%), partially engaged (32/214, 15%), and unengaged (103/214, 48.1%) users. Married parents were more likely to be fullyengaged than independently engaged (P=.02) or unengaged (P=.01) users. Socially engaged parents were older than fullyengaged (P=.02) and unengaged (P=.01) parents. The latent class analysis revealed 4 phenotypes among children: fully engaged (32/214, 15%), partially engaged (61/214, 28.5%), dabblers (42/214, 19.6%), and unengaged (79/214, 36.9%) users. Fully engaged children were younger than dabblers (P=.04) and unengaged (P=.003) children. Dabblers lived in higher-income households than fully and partiallyengaged children (P=.03 and P=.047, respectively). Fully engaged children were more likely to have fully engaged (P<.001) and partiallyengaged (P<.001) parents than unengaged children. Compared with unengaged children, fully and partiallyengaged children had decreased total sugar (P=.006 and P=.004, respectively) and energy intake (P=.03 and P=.04, respectively) after 3 months of app use. Partially engaged children also had decreased sugary beverage intake compared with unengaged children (P=.03). Similarly, children with fully engaged parents had decreased zBMI, whereas children with unengaged parents had increased zBMI over time (P=.005). Finally, children with independently engaged parents had decreased caloric intake, whereas children with unengaged parents had increased caloric intake over time (P=.02).
Full parent-child engagement is critical for the success of mHealth interventions. Further research is needed to understand program design elements that can affect participants' engagement in supporting behavior change.
ClinicalTrials.gov NCT03651284; https://clinicaltrials.gov/ct2/show/NCT03651284.
RR2-10.1186/s13063-020-4080-2.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Aim2Be is a gamified lifestyle app designed to promote lifestyle behavior changes among Canadian adolescents and their families.
The primary aim was to test the efficacy of the Aim2Be app with ...support from a live coach to reduce weight outcomes (BMI Z score zBMI) and improve lifestyle behaviors among adolescents with overweight and obesity and their parents versus a waitlist control group over 3 months. The secondary aim was to compare health trajectories among waitlist control participants over 6 months (before and after receiving access to the app), assess whether support from a live coach enhanced intervention impact, and evaluate whether the app use influenced changes among intervention participants.
A 2-arm parallel randomized controlled trial was conducted from November 2018 to June 2020. Adolescents aged 10 to 17 years with overweight or obesity and their parents were randomized into an intervention group (Aim2Be with a live coach for 6 months) or a waitlist control group (Aim2Be with no live coach; accessed after 3 months). Adolescents' assessments at baseline and at 3 and 6 months included measured height and weight, 24-hour dietary recalls, and daily step counts measured with a Fitbit. Data on self-reported physical activity, screen time, fruit and vegetable intake, and sugary beverage intake of adolescents and parents were also collected.
A total of 214 parent-child participants were randomized. In our primary analyses, there were no significant differences in zBMI or any of the health behaviors between the intervention and control groups at 3 months. In our secondary analyses, among waitlist control participants, zBMI (P=.02), discretionary calories (P=.03), and physical activity outside of school (P=.001) declined, whereas daily screen time increased (P<.001) after receiving access to the app compared with before receiving app access. Adolescents randomized to Aim2Be with live coaching reported more time being active outside of school compared with adolescents who used Aim2Be with no coaching over 3 months (P=.001). App use did not modify any changes in outcomes among adolescents in the intervention group.
The Aim2Be intervention did not improve zBMI and lifestyle behaviors in adolescents with overweight and obesity compared with the waitlist control group over 3 months. Future studies should explore the potential mediators of changes in zBMI and lifestyle behaviors as well as predictors of engagement.
ClinicalTrials.gov NCT03651284; https://clinicaltrials.gov/ct2/show/study/NCT03651284.
RR2-10.1186/s13063-020-4080-2.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
•Mothers had limited knowledge of infant/toddler sweetened beverage recommendations.•Knowledge of physical activity/sedentary time for infants/toddlers was also limited.•Future targeted educational ...programs may be beneficial.
Infants born to mothers with type 2 diabetes (T2D) and gestational diabetes (GDM) are at an increased risk of being overweight/obese. Modifiable lifestyle factors play a role in prevention of overweight and obesity. In 2017, the Canadian 24 h Movement Guidelines for the Early Years (CMG) were released. Alongside physical activity recommendations, sweetened beverage consumption (SBC) recommendations were also released by the American Academy of Pediatrics in 2017. The objective of this study was to determine the knowledge pregnant women with T2D and GDM have on the CMG and SBC recommendations, and to determine what factors affect this. A survey with questions regarding demographics, socioeconomic variables and the CMG and SBC recommendations was administered to pregnant women at Diabetes in Pregnancy clinics in Calgary, Alberta from July 2019 to January 2020. Surveys were analyzed utilizing the non-parametric Kruskall-Wallis Rank-Sum test, chi-square test and linear regression. A total of 79 respondents with T2D and GDM were collected. Respondents had the highest knowledge of SBC recommendations and the lowest knowledge of CMG recommendations. A bachelor’s or higher degree was associated with significantly higher knowledge scores than a high-school education or less. In conclusion, pregnant women with T2D and GDM in this study had overall poor knowledge of the CMG and SBC recommendations, with less knowledge regarding the CMG. Level of education was found to be associated with knowledge regarding these recommendations. Future programs to improve education around infant and toddler physical activity and SBC recommendations may be beneficial for this patient population.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The prevalence of overweight and obesity remains high in Canada, and the current standard for the treatment of childhood obesity is in-person, family-based, multidisciplinary interventions that ...target lifestyle behaviors (e.g., diet, physical activity, and sedentary behaviors). These programs are costly to operate, have limited success, and report recruitment and retention challenges. With recent advances in technology, mobile health or mHealth has been presented as a viable alternative to in-person interventions for behavior change, especially with teens.
The primary aim of this study is to test the efficacy of Aim2Be, a gamified app based on behavior change theory with health coaching to improve weight outcomes (i.e., decrease in standardized body mass index (zBMI)) and lifestyle behaviors (i.e., improve dietary quality, increase fruit and vegetable intake, reduce sugar-sweetened beverage intake, increase physical activity, and reduce screen time) among children 10- to 17-years old with overweight or obesity versus their peers randomized into a waitlist control condition. The secondary aims of this study are to 1) test whether supplementing the Aim2Be program with health coaching increases adherence and 2) examine the mediators and moderators of adherence to the Aim2Be intervention.
We will employ a randomized controlled trial design and recruit 200 child and parent dyads to participate in the study (2019-2020). Participants will be recruited from Canadian pediatric weight management clinics and through online advertisements. Child participants must be between the ages of 10 and 17 years, have overweight or obesity, be able to read English at least at a grade 5 level, and have a mobile phone or home computer with internet access. Following baseline data collection, participants will be randomized into intervention and waitlist control groups. Intervention participants will receive access to Aim2Be, with access to health coaching. After having their data collected for 3 months, the control group will gain access to Aim2Be, with no access to health coaching. Participants will control their frequency and duration of app usage to promote autonomy.
Findings from this study will determine the efficacy of using Aim2Be in improving child weight outcomes and lifestyle behaviors and guide future mHealth interventions for pediatric weight management.
ClinicalTrials.gov, NCT03651284. Registered 29 August 2018.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Mammalian SWI/SNF complexes are multi-subunit chromatin remodeling complexes associated with an ATPase (either SMARCA4 or SMARCA2). Heterozygous mutations in the SMARCA2 ATPase cause ...Nicolaides-Baraitser syndrome (NCBRS), an intellectual disability syndrome associated with delayed speech onset. We engineered human embryonic stem cells (hESCs) to carry NCBRS-associated heterozygous SMARCA2 K755R or R1159Q mutations. While SMARCA2 mutant hESCs were phenotypically normal, differentiation to neural progenitors cells (NPCs) was severely impaired. We find that SMARCA2 mutations cause enhancer reorganization with loss of SOX3-dependent neural enhancers and prominent emergence of astrocyte-specific de novo enhancers. Changes in chromatin accessibility at enhancers were associated with an increase in SMARCA2 binding and retargeting of SMARCA4. We show that the AP-1 family member FRA2 is aberrantly overexpressed in SMARCA2 mutant NPCs, where it functions as a pioneer factor at de novo enhancers. Together, our results demonstrate that SMARCA2 mutations cause impaired differentiation through enhancer reprogramming via inappropriate targeting of SMARCA4.
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•Heterozygous missense mutations in SMARCA2 impair neural differentiation•SMARCA2 mutations result in enhancer reprogramming due to SMARCA4 retargeting•SOX3-dependent neural enhancers are lost in SMARCA2 mutant neural progenitor cells•AP-1 factors drive de novo enhancer formation in SMARCA2 mutant cells
Mutations in subunits of the SWI/SNF complex cause developmental disorders associated with intellectual disability and speech delay. However, the mechanistic basis of disease is poorly understood. Gao et al. show that disease-associated SMARCA2 mutations lead to impaired neural differentiation due to changes in transcription factor expression that drive enhancer reprogramming.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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