Despite the potential benefits of mobile mental health apps, real-world results indicate engagement issues because of low uptake and sustained use. This review examined how studies have measured and ...reported on user engagement indicators (UEIs) for mental health apps.
A systematic review of multiple databases was performed in July 2018 for studies of mental health apps for depression, bipolar disorder, schizophrenia, and anxiety that reported on UEIs, namely usability, user satisfaction, acceptability, and feasibility. The subjective and objective criteria used to assess UEIs, among other data, were extracted from each study.
Of 925 results, 40 studies were eligible. Every study reported positive results for the usability, satisfaction, acceptability, or feasibility of the app. Of the 40 studies, 36 (90%) employed 371 indistinct subjective criteria that were assessed with surveys, interviews, or both, and 23 studies used custom subjective scales, rather than preexisting standardized assessment tools. A total of 25 studies (63%) used objective criteria-with 71 indistinct measures. No two studies used the same combination of subjective or objective criteria to assess UEIs of the app.
The high heterogeneity and use of custom criteria to assess mental health apps in terms of usability, user satisfaction, acceptability, or feasibility present a challenge for understanding real-world low uptake of these apps. Every study reviewed claimed that UEIs for the app were rated highly, which suggests a need for the field to focus on engagement by creating reporting standards and more carefully considering claims.
Background
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people ...around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed.
Methods
We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the
Grading of Recommendations, Assessment, Development and Evaluation
(GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations.
Results
The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which 4 are best practice statements, 9 are strong recommendations, and 35 are weak recommendations. No recommendation was provided for 6 questions. The topics were: (1) infection control, (2) laboratory diagnosis and specimens, (3) hemodynamic support, (4) ventilatory support, and (5) COVID-19 therapy.
Conclusion
The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new recommendations in further releases of these guidelines.
The response to DNA damage, which regulates nuclear processes such as DNA repair, transcription, and cell cycle, has been studied thoroughly. However, the cytoplasmic response to DNA damage is poorly ...understood. Here, we demonstrate that DNA damage triggers dramatic reorganization of the Golgi, resulting in its dispersal throughout the cytoplasm. We further show that DNA-damage-induced Golgi dispersal requires GOLPH3/MYO18A/F-actin and the DNA damage protein kinase, DNA-PK. In response to DNA damage, DNA-PK phosphorylates GOLPH3, resulting in increased interaction with MYO18A, which applies a tensile force to the Golgi. Interference with the Golgi DNA damage response by depletion of DNA-PK, GOLPH3, or MYO18A reduces survival after DNA damage, whereas overexpression of GOLPH3, as is observed frequently in human cancers, confers resistance to killing by DNA-damaging agents. Identification of the DNA-damage-induced Golgi response reveals an unexpected pathway through DNA-PK, GOLPH3, and MYO18A that regulates cell survival following DNA damage.
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•DNA damage triggers Golgi dispersal•DNA damage signals directly to the Golgi via DNA-PK phosphorylation of GOLPH3•Golgi proteins GOLPH3 and MYO18A are required for survival after DNA damage•GOLPH3 overexpression, as seen in cancer, confers resistance to DNA-damaging agents
The cellular response to DNA-damaging agents underlies the effectiveness of many cancer therapeutics. This paper now demonstrates that DNA damage triggers a dramatic reorganization of the Golgi through DNA-PK- and GOLPH3-mediated signaling, playing a significant role in cell survival.
Abstract
Genome editing with the CRISPR-Cas9 system has enabled unprecedented efficacy for reverse genetics and gene correction approaches. While off-target effects have been successfully tackled, ...the effort to eliminate variability in sgRNA efficacies-which affect experimental sensitivity-is in its infancy. To address this issue, studies have analyzed the molecular features of highly active sgRNAs, but independent cross-validation is lacking. Utilizing fluorescent reporter knock-out assays with verification at selected endogenous loci, we experimentally quantified the target efficacies of 430 sgRNAs. Based on this dataset we tested the predictive value of five recently-established prediction algorithms. Our analysis revealed a moderate correlation (r = 0.04 to r = 0.20) between the predicted and measured activity of the sgRNAs, and modest concordance between the different algorithms. We uncovered a strong PAM-distal GC-content-dependent activity, which enabled the exclusion of inactive sgRNAs. By deriving nine additional predictive features we generated a linear model-based discrete system for the efficient selection (r = 0.4) of effective sgRNAs (CRISPRater). We proved our algorithms' efficacy on small and large external datasets, and provide a versatile combined on- and off-target sgRNA scanning platform. Altogether, our study highlights current issues and efforts in sgRNA efficacy prediction, and provides an easily-applicable discrete system for selecting efficient sgRNAs.
Vesicle budding for Golgi-to-plasma membrane trafficking is a key step in secretion. Proteins that induce curvature of the Golgi membrane are predicted to be required, by analogy to vesicle budding ...from other membranes. Here, we demonstrate that GOLPH3, upon binding to the phosphoinositide PI4P, induces curvature of synthetic membranes in vitro and the Golgi in cells. Moreover, efficient Golgi-to-plasma membrane trafficking critically depends on the ability of GOLPH3 to curve the Golgi membrane. Interestingly, uncoupling of GOLPH3 from its binding partner MYO18A results in extensive curvature of Golgi membranes, producing dramatic tubulation of the Golgi, but does not support forward trafficking. Thus, forward trafficking from the Golgi to the plasma membrane requires the ability of GOLPH3 both to induce Golgi membrane curvature and to recruit MYO18A. These data provide fundamental insight into the mechanism of Golgi trafficking and into the function of the unique Golgi secretory oncoproteins GOLPH3 and MYO18A.
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•GOLPH3 induces curvature of liposomes in vitro and the Golgi in cells•GOLPH3 induces curvature by insertion of a hydrophobic β-loop into the bilayer•Efficient Golgi-to-plasma membrane trafficking depends on GOLPH3-induced curvature•Golgi-to-plasma membrane trafficking also requires GOLPH3 interaction with MYO18A
Rahajeng et al. show that GOLPH3, upon binding to PtdIns(4)P-containing lipid bilayers, induces membrane curvature. This membrane-shaping activity of GOLPH3 is required for efficient Golgi-to-plasma membrane trafficking but is not sufficient. GOLPH3 also must recruit MYO18A to the Golgi to enable efficient forward trafficking.
To measure the impact of staged implementation of full versus partial ABCDE bundle on mechanical ventilation duration, ICU and hospital lengths of stay, and cost.
Prospective cohort study.
Two ...medical ICUs within Montefiore Healthcare Center (Bronx, NY).
One thousand eight hundred fifty-five mechanically ventilated patients admitted to ICUs between July 2011 and July 2014.
At baseline, spontaneous (B)reathing trials (B) were ongoing in both ICUs; in period 1, (A)wakening and (D)elirium (AD) were implemented in both full and partial bundle ICUs; in period 2, (E)arly mobilization and structured bundle (C)oordination (EC) were implemented in the full bundle (B-AD-EC) but not the partial bundle ICU (B-AD).
In the full bundle ICU, 95% patient days were spent in bed before EC (period 1). After EC was implemented (period 2), 65% of patients stood, 54% walked at least once during their ICU stay, and ICU-acquired pressure ulcers and physical restraint use decreased (period 1 vs 2: 39% vs 23% of patients; 30% vs 26% patient days, respectively; p < 0.001 for both). After adjustment for patient-level covariates, implementation of the full (B-AD-EC) versus partial (B-AD) bundle was associated with reduced mechanical ventilation duration (-22.3%; 95% CI, -22.5% to -22.0%; p < 0.001), ICU length of stay (-10.3%; 95% CI, -15.6% to -4.7%; p = 0.028), and hospital length of stay (-7.8%; 95% CI, -8.7% to -6.9%; p = 0.006). Total ICU and hospital cost were also reduced by 24.2% (95% CI, -41.4% to -2.0%; p = 0.03) and 30.2% (95% CI, -46.1% to -9.5%; p = 0.007), respectively.
In a clinical practice setting, the addition of (E)arly mobilization and structured (C)oordination of ABCDE bundle components to a spontaneous (B)reathing, (A)wakening, and (D) elirium management background led to substantial reductions in the duration of mechanical ventilation, length of stay, and cost.
Promoting healthy eating habits can prevent adolescent obesity in which family may play a significant role. This review synthesized findings from qualitative studies to identify family barriers and ...facilitators of adolescent healthy eating in terms of knowledge, attitudes, and practices (KAP). A literature search of four databases was completed on 31 July 2020; qualitative studies that explored family factors of adolescent (aged 10 to 19 years) eating habits were included. A total of 48 studies were identified, with the majority being from North America and sampled from a single source. Ten themes on how family influences adolescent dietary KAP were found: Knowledge—(1) parental education, (2) parenting style, and (3) family illness experience; Attitudes—(4) family health, (5) cultivation of preference, and (6) family motivation; Practices—(7) home meals and food availability, (8) time and cost, (9) parenting style, and (10) parental practical knowledge and attitudes. This review highlights five parental characteristics underlying food parenting practices which affect adolescents’ KAP on healthy eating. Adolescents with working parents and who are living in low-income families are more vulnerable to unhealthy eating. There is a need to explore cultural-specific family influences on adolescents’ KAP, especially regarding attitudes and food choices in Asian families.
Physical activity is essential for children's healthy development, yet COVID-19 physical distancing restrictions such as school closures and staying at home, playground closures, and the cancelling ...of organised community sport have dramatically altered children's opportunities to be physically active. This study describes changes in levels of physical activity and screen time from February 2020 (i.e., before COVID-19 restrictions were introduced in Western Australia) to May 2020 (i.e., when COVID-19 restrictions were in place). Parents of children aged 5 to 9 years from Western Australia were eligible to participate and recruited through convenience sampling. An online survey instrument that included validated measures of their children's physical activity (unstructured, organized, home-based, indoor/outdoor active play, dog play/walking), sociodemographic, and other potential confounders was administered to parents. Paired
-tests and mixed ANOVA models assessed changes in physical activity outcomes. The analytic sample comprised parents of 157 children who were 6.9 years of age (SD = 1.7) on average. Overall, weekly minutes of total physical activity (PA) did not change from before to during COVID-19. However, frequency and duration (total and home-based) of unstructured physical activity significantly increased. Outdoor play in the yard or street around the house, outdoor play in the park or playground or outdoor recreation area, and active indoor play at home all significantly increased. Frequency and total duration of organised physical activity significantly declined during COVID-19 distancing. During Western Australian COVID-19 restrictions, there was an increase in young children's unstructured physical activity and outdoor play and a decrease in organised physical activity. It remains to be seen whether children's increased physical activity has been sustained with the easing of physical distancing restrictions.
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