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BackgroundIn March 2020, Text4Hope—a community health service—was provided to Alberta residents. This free service aims to promote psychological resilience and alleviate pandemic-associated stress, anxiety, and depression symptoms during the COVID-19 pandemic. ObjectiveThis study aimed to evaluate the feedback, satisfaction, experience, and perceptions of Text4Hope subscribers and to examine any differences based on gender after subscribers received 6 weeks of daily supportive text messages. Additionally, this study examined subscribers’ anticipated receptivity to technology-based medical services that could be offered during major crises, emergencies, or pandemics. MethodsIndividuals self-subscribed to Text4Hope to receive daily supportive text messages for 3 months. Subscribers were invited to complete a web-based survey at 6 weeks postintervention to provide service satisfaction–related information. Overall satisfaction was assessed on a scale of 0-10, and satisfaction scores were analyzed using a related-measures t test. Likert scale satisfaction responses were used to assess various aspects of the Text4Hope program. Gender differences were analyzed using one-way analysis of variance (ANOVA) and Chi-square analyses. ResultsA total of 2032 subscribers completed the baseline and 6-week surveys; 1788 (88%) were female, 219 (10.8%) were male, and 25 (1.2%) were other gender. The mean age of study participants was 44.58 years (SD 13.45 years). The mean overall satisfaction score was 8.55 (SD 1.78), suggesting high overall satisfaction with Text4Hope. The ANOVA analysis, which was conducted using the Welch test (n=1716), demonstrated that females had significantly higher mean satisfaction scores than males (8.65 vs 8.11, respectively; mean difference=0.546; 95% CI 0.19 to 0.91; P

BackgroundIn addition to the obvious physical medical impact of COVID-19, the disease poses evident threats to people’s mental health, psychological safety, and well-being. Provision of support for these challenges is complicated by the high number of people requiring support and the need to maintain physical distancing. Text4Hope, a daily supportive SMS text messaging program, was launched in Canada to mitigate the negative mental health impacts of the pandemic among Canadians. ObjectiveThis paper describes the changes in the stress, anxiety, and depression levels of subscribers to the Text4Hope program after 6 weeks of exposure to daily supportive SMS text messages. MethodsWe used self-administered, empirically supported web-based questionnaires to assess the demographic and clinical characteristics of Text4Hope subscribers. Perceived stress, anxiety, and depression were measured with the 10-Item Perceived Stress Scale (PSS-10), the Generalized Anxiety Disorder–7 (GAD-7) scale, and the Patient Health Questionnaire–9 (PHQ-9) scale at baseline and sixth week time points. Moderate or high perceived stress, likely generalized anxiety disorder, and likely major depressive disorder were assessed using cutoff scores of ≥14 for the PSS-10, ≥10 for the GAD-7, and ≥10 for the PHQ-9, respectively. At 6 weeks into the program, 766 participants had completed the questionnaires at both time points. ResultsAt the 6-week time point, there were statistically significant reductions in mean scores on the PSS-10 and GAD-7 scales but not on the PHQ-9 scale. Effect sizes were small overall. There were statistically significant reductions in the prevalence rates of moderate or high stress and likely generalized anxiety disorder but not likely major depressive disorder for the group that completed both the baseline and 6-week assessments. The largest reductions in mean scores and prevalence rates were for anxiety (18.7% and 13.5%, respectively). ConclusionsText4Hope is a convenient, cost-effective, and accessible means of implementing a population-level psychological intervention. This service demonstrated significant reductions in anxiety and stress levels during the COVID-19 pandemic and could be used as a population-level mental health intervention during natural disasters and other emergencies. International Registered Report Identifier (IRRID)RR2-10.2196/19292

BackgroundDuring pandemics, effective containment and mitigation measures may also negatively influence psychological stability. As knowledge about COVID-19 rapidly evolves, global implementation of containment and mitigation measures has varied greatly, with impacts to mental wellness. Assessing the impact of COVID-19 on the mental health needs of health care workers and other workers may help mitigate mental health impacts and secure sustained delivery of health care and other essential goods and services. ObjectiveThis study assessed the self-reported prevalence of stress, anxiety, depression, and obsessive-compulsive symptoms in health care workers and other workers seeking support through Text4Hope, an evidence-based SMS text messaging service supporting the mental health of residents of Alberta, Canada, during the COVID-19 pandemic. MethodsAn online cross-sectional survey gathered demographic (age, gender, ethnicity, education, relationship, housing and employment status, employment type, and isolation status) and clinical characteristics using validated tools (self-reported stress, anxiety, depression, and contamination/hand hygiene obsessive-compulsive symptoms). Descriptive statistics and chi-square analysis were used to compare the clinical characteristics of health care workers and other workers. Post hoc analysis was conducted on variables with >3 response categories using adjusted residuals. Logistic regression determined associations between worker type and likelihood of self-reported symptoms of moderate or high stress, generalized anxiety disorder, and major depressive disorder, while controlling for other variables. ResultsOverall, 8267 surveys were submitted by 44,992 Text4Hope subscribers (19.39%). Of these, 5990 respondents were employed (72.5%), 958 (11.6%) were unemployed, 454 (5.5%) were students, 559 (6.8%) were retired, 234 (2.8%) selected “other,” and 72 (0.9%) did not indicate their employment status. Most employed survey respondents were female (n=4621, 86.2%). In the general sample, the 6-week prevalence rates for moderate or high stress, anxiety, and depression symptoms were 85.6%, 47.0%, and 44.0%, respectively. Self-reported symptoms of moderate or high stress, anxiety, and depression were all statistically significantly higher in other workers than in health care workers (P

BackgroundCoronavirus disease (COVID-19) has spread globally with far-reaching, significant, and unprecedented impacts on health and everyday life. Threats to mental health, psychological safety, and well-being are now emerging, increasing the impact of this virus on world health. Providing support for these challenges is difficult because of the high number of people requiring support in the context of a need to maintain physical distancing. This protocol describes the use of SMS text messaging (Text4Hope) as a convenient, cost-effective, and accessible population-level mental health intervention. This program is evidence-based, with prior research supporting good outcomes and high user satisfaction. ObjectiveThe project goal is to implement a program of daily supportive SMS text messaging (Text4Hope) to reduce distress related to the COVID-19 crisis, initially among Canadians. The prevalence of stress, anxiety, and depressive symptoms; the demographic correlates of the same; and the outcomes of the Text4Hope intervention in mitigating distress will be evaluated. MethodsSelf-administered anonymous online questionnaires will be used to assess stress (Perceived Stress Scale), anxiety (Generalized Anxiety Disorder-7 scale [GAD-7]), and depressive symptoms (Patient Health Questionnaire-9 [PHQ-9]). Data will be collected at baseline (onset of SMS text messaging), the program midpoint (6 weeks), and the program endpoint (12 weeks). ResultsData analysis will include parametric and nonparametric techniques, focusing on primary outcomes (ie, stress, anxiety, and depressive symptoms) and metrics of use, including the number of subscribers and user satisfaction. Given the large size of the data set, machine learning and data mining methods will also be used. ConclusionsThis COVID-19 project will provide key information regarding prevalence rates of stress, anxiety, and depressive symptoms during the pandemic; demographic correlates of distress; and outcome data related to this scalable population-level intervention. Information from this study will be valuable for practitioners and useful for informing policy and decision making regarding psychological interventions during the pandemic. International Registered Report Identifier (IRRID)DERR1-10.2196/19292

Biological shape diversity is often manifested in modulation of organ symmetry and modification of the patterned elaboration of repeated shape elements. 1,2,3,4,5 Whether and how these two aspects of shape determination are coordinately regulated is unclear. 5,6,7 Plant leaves provide an attractive system to investigate this problem, because they often show asymmetries along the proximodistal (PD) axis of their blades, along which they can also produce repeated marginal outgrowths such as serrations or leaflets. 1 One aspect of leaf shape diversity is heteroblasty, where the leaf form in a single genotype is modified with progressive plant age. 8,9,10,11 In Arabidopsis thaliana, a plant with simple leaves, SQUAMOSA PROMOTER BINDING PROTEIN-LIKE 9 (SPL9) controls heteroblasty by activating CyclinD3 expression, thereby sustaining proliferative growth and retarding differentiation in adult leaves. 12,13 However, the precise significance of SPL9 action for leaf symmetry and marginal patterning is unknown. By combining genetics, quantitative shape analyses, and time-lapse imaging, we show that PD symmetry of the leaf blade in A. thaliana decreases in response to an age-dependent SPL9 expression gradient, and that SPL9 action coordinately regulates the distribution and shape of marginal serrations and overall leaf form. Using comparative analyses, we demonstrate that heteroblastic growth reprogramming in Cardamine hirsuta, a complex-leafed relative of A. thaliana, also involves prolonging the duration of cell proliferation and delaying differentiation. We further provide evidence that SPL9 enables species-specific action of homeobox genes that promote leaf complexity. In conclusion, we identified an age-dependent layer of organ PD growth regulation that modulates leaf symmetry and has enabled leaf shape diversification. [Display omitted] • An age-dependent growth gradient underpins regulation of A. thaliana leaf symmetry • SPL9-mediated heteroblastic growth control potentiates leaf histogenic capacity • Common growth patterns underlie heteroblasty in complex and simple leaves • SPL9 enables the action of homeobox genes that promote leaf complexity Li et al. study mechanisms underlying age-dependent changes in leaf symmetry and margin shape. They show that SPL9-mediated regulation of proliferative growth and differentiation along the leaf proximodistal axis modulates organ symmetry and marginal patterning and enables the action of homeobox genes that contributed to complex leaf shape evolution. [ABSTRACT FROM AUTHOR]

Myeloperoxidase (MPO) and paraoxonase 1 (PON1) are high-density lipoprotein-associated (HDL-associated) proteins mechanistically linked to inflammation, oxidant stress, and atherosclerosis. MPO is a source of ROS during inflammation and can oxidize apolipoprotein A1 (APOA1) of HDL, impairing its atheroprotective functions. In contrast, PON1 fosters systemic antioxidant effects and promotes some of the atheroprotective properties attributed to HDL. Here, we demonstrate that MPO, PON1, and HDL bind to one another, forming a ternary complex, wherein PON1 partially inhibits MPO activity, while MPO inactivates PON1. MPO oxidizes PON1 on tyrosine 71 (Tyr71), a modified residue found in human atheroma that is critical for HDL binding and PON1 function. Acute inflammation model studies with transgenic and knockout mice for either PON1 or MPO confirmed that MPO and PON1 reciprocally modulate each others function in vivo. Further structure and function studies identified critical contact sites between APOA1 within HDL, PON1, and MPO, and proteomics studies of HDL recovered from acute coronary syndrome (ACS) subjects revealed enhanced chlorotyrosine content, site-specific PON1 methionine oxidation, and reduced PON1 activity. HDL thus serves as a scaffold upon which MPO and PON1 interact during inflammation, whereupon PON1 binding partially inhibits MPO activity, and MPO promotes site-specific oxidative modification and impairment of PON1 and APOA1 function.

PIWI‐interacting RNAs (piRNAs) are highly expressed in various cardiovascular diseases. However, their role in cardiomyocyte death caused by ischemia/reperfusion (I/R) injury, especially necroptosis, remains elusive. In this study, a heart necroptosis‐associated piRNA (HNEAP) is found that regulates cardiomyocyte necroptosis by targeting DNA methyltransferase 1 (DNMT1)‐mediated 5‐methylcytosine (m5C) methylation of the activating transcription factor 7 (Atf7) mRNA transcript. HNEAP expression level is significantly elevated in hypoxia/reoxygenation (H/R)‐exposed cardiomyocytes and I/R‐injured mouse hearts. Loss of HNEAP inhibited cardiomyocyte necroptosis and ameliorated cardiac function in mice. Mechanistically, HNEAP directly interacts with DNMT1 and attenuates m5C methylation of the Atf7 mRNA transcript, which increases Atf7 expression level. ATF7 can further downregulate the transcription of Chmp2a, an inhibitor of necroptosis, resulting in the reduction of Chmp2a level and the progression of cardiomyocyte necroptosis. The findings reveal that piRNA‐mediated m5C methylation is involved in the regulation of cardiomyocyte necroptosis. Thus, the HNEAP‐DNMT1‐ATF7‐CHMP2A axis may be a potential target for attenuating cardiac injury caused by necroptosis in ischemic heart disease. [ABSTRACT FROM AUTHOR]