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The heart forms early in development and delivers oxygenated blood to the rest of the embryo. After birth, the heart requires kilograms of ATP each day to support contractility for the circulation. Cardiac metabolism is omnivorous, utilizing multiple substrates and metabolic pathways to produce this energy. Cardiac development, metabolic tuning, and the response to ischemia are all regulated in part by the hypoxia-inducible factors (HIFs), central components of essential signaling pathways that respond to hypoxia. Here we review the actions of HIF1, HIF2, and HIF3 in the heart, from their roles in development and metabolism to their activity in regeneration and preconditioning strategies. We also discuss recent work on the role of HIFs in atherosclerosis, the precipitating cause of myocardial ischemia and the leading cause of death in the developed world.The heart forms early in development and delivers oxygenated blood to the rest of the embryo. After birth, the heart requires kilograms of ATP each day to support contractility for the circulation. Cardiac metabolism is omnivorous, utilizing multiple substrates and metabolic pathways to produce this energy. Cardiac development, metabolic tuning, and the response to ischemia are all regulated in part by the hypoxia-inducible factors (HIFs), central components of essential signaling pathways that respond to hypoxia. Here we review the actions of HIF1, HIF2, and HIF3 in the heart, from their roles in development and metabolism to their activity in regeneration and preconditioning strategies. We also discuss recent work on the role of HIFs in atherosclerosis, the precipitating cause of myocardial ischemia and the leading cause of death in the developed world.

How the stressosome, the epicenter of the stress response in bacteria, transmits stress signals from the environment has remained elusive. The stressosome consists of multiple copies of three proteins RsbR, RsbS and RsbT, a kinase that is important for its activation. Using cryo-electron microscopy, we determined the atomic organization of the Listeria monocytogenes stressosome at 3.38 Å resolution. RsbR and RsbS are organized in a 60-protomers truncated icosahedron. A key phosphorylation site on RsbR (T209) is partially hidden by an RsbR flexible loop, whose “open” or “closed” position could modulate stressosome activity. Interaction between three glutamic acids in the N-terminal domain of RsbR and the membrane-bound mini-protein Prli42 is essential for Listeria survival to stress. Together, our data provide the atomic model of the stressosome core and highlight a loop important for stressosome activation, paving the way towards elucidating the mechanism of signal transduction by the stressosome in bacteria. The bacterial stressosome is a large nanomachine and a key inducer of stress response. Here, the authors present the cryo-EM structure of the stressosome from the bacterial pathogen Listeria monocytogenes at 3.38 Å resolution and discuss its activation mechanism.

In the gastric pathogen Helicobacter pylori , post-transcriptional regulation relies strongly on the activity of the essential ribonuclease RNase J. Here, we elucidated the crystal and cryo-EM structures of RNase J and determined that it assembles into dimers and tetramers in vitro. We found that RNase J extracted from H. pylori is acetylated on multiple lysine residues. Alanine substitution of several of these residues impacts on H. pylori morphology, and thus on RNase J function in vivo. Mutations of Lysine 649 modulates RNase J oligomerization in vitro, which in turn influences ribonuclease activity in vitro. Our structural analyses of RNase J reveal loops that gate access to the active site and rationalizes how acetylation state of K649 can influence activity. We propose acetylation as a regulatory level controlling the activity of RNase J and its potential cooperation with other enzymes of RNA metabolism in H. pylori . Here the authors find that RNase J, the major ribonuclease of the gastric pathogen Helicobacter pylori is post-translationally modified by acetylation. They show that acetylation can control RNase J activity.

Background The status of randomised controlled trials (RCTs) as the ‘gold standard’ for evaluating efficacy in healthcare interventions is increasingly debated among the research community, due to often insufficient consideration for implementation. Normalisation Process Theory (NPT), which focuses on the work required to embed processes into practice, offers a potentially useful framework for addressing these concerns. While the theory has been deployed in numerous RCTs to date, more work is needed to consolidate understanding of if, and how, NPT may aid implementation planning and processes within RCTs. Therefore, this review seeks to understand how NPT contributes to understanding the dynamics of implementation processes within RCTs. Specifically, this review will identify and characterise NPT operationalisation, benefits and reported challenges and limitations in RCTs. Methods A qualitative systematic review with narrative synthesis of peer-reviewed journal articles from eight databases was conducted. Studies were eligible for inclusion if they reported sufficient detail on the use of NPT within RCTs in a healthcare domain. A pre-specified data extraction template was developed based on the research questions of this review. A narrative synthesis was performed to identify recurrent findings. Results Searches identified 48 articles reporting 42 studies eligible for inclusion. Findings suggest that NPT is primarily operationalised prospectively during the data collection stage, with limited sub-construct utilisation overall. NPT is beneficial in understanding implementation processes by aiding the identification and analysis of key factors, such as understanding intervention fidelity in real-world settings. Nearly three-quarters of studies failed to report the challenges and limitations of utilising NPT, though coding difficulties and data falling outside the NPT framework are most common. Conclusions NPT appears to be a consistent and generalisable framework for explaining the dynamics of implementation processes within RCTs. However, operationalisation of the theory to its full extent is necessary to improve its use in practice, as it is currently deployed in varying capacities. Recommendations for future research include investigation of NPT alongside other frameworks, as well as earlier operationalisation and greater use of NPT sub-constructs. Trial Registration The protocol for this systematic review was accepted for public registration on PROSPERO (registration number: CRD42022345427) on 26 July 2022.

Mobile health apps (MHAs) are increasingly used in modern health care provision. The technology acceptance model (TAM) is the most widely used framework for predicting health care technology acceptance. Since the advent of this model in 1989, technology has made generational advancements, and extensions of this model have been implemented. This systematic review aimed to re-examine TAM models to establish their validity for predicting the acceptance of modern MHAs, reviewing relevant core and extended constructs, and the relationships between them. In this systematic review, MEDLINE, Embase, Global Health, APA PsycINFO, CINAHL, and Scopus databases were searched on March 8, 2024, with no time constraints, for studies assessing the use of TAM-based frameworks for MHA acceptance. Studies eligible for data extraction were required to be peer-reviewed, English-language, primary research articles evaluating MHAs with health-related utility, using TAM as the primary technology acceptance evaluation framework, and reporting app use data. Data were extracted and grouped into 5 extended TAM construct themes. Quality assessment was conducted using the Joanna Briggs Institute (JBI) tools. For cross-sectional methodologies (9/14, 64%), the JBI checklist for analytical cross-sectional studies was used. For non-cross-sectional studies (5/14, 36%), the JBI checklist most relevant to the specific study design was used. For mixed methods studies (1/14, 7%), the JBI checklist for qualitative studies was applied, in addition to the JBI checklist most suited to the quantitative design. A subsequent narrative synthesis was conducted in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology. A total of 2790 records were identified, and 14 were included. Furthermore, 10 studies validated the efficacy of TAM and its extensions for the assessment of MHAs. Relationships between core TAM constructs (perceived usefulness, perceived ease of use, and behavioral intention) were validated. Extended TAM constructs were grouped into 5 themes: health risk, application factors, social factors, digital literacy, and trust. Digital literacy, trust, and application factor extended construct themes had significant predictive capacity. Application factors had the strongest MHA acceptance predictive capabilities. Perceived usefulness and extended constructs related to social factors, design aesthetics, and personalization were more influential for those from deprived socioeconomic backgrounds. TAM is an effective framework for evaluating MHA acceptance. While original TAM constructs wield significant predictive capacity, the incorporation of social and clinical context-specific extended TAM constructs can enhance the model's predictive capabilities. This review's findings can be applied to optimize MHAs' user engagement and minimize health care inequalities. Our findings also underscore the necessity of adapting TAM and other acceptability frameworks as the technological and social landscape evolves. PROSPERO CRD42024532974; https://www.crd.york.ac.uk/PROSPERO/view/CRD42024532974.

Despite the mounting evidence linking loneliness with health, the mechanisms underlying this relationship remain obscure. This systematic review and meta-analysis on the association between loneliness and one potential mechanism—sleep—identified 27 relevant articles. Loneliness correlated with self-reported sleep disturbance (r = .28, 95% confidence interval (.24, .33)) but not duration, across a diverse set of samples and measures. There was no evidence supporting age or gender as moderators or suggesting publication bias. The longitudinal relationship between loneliness and sleep remains unclear. Loneliness is related to sleep disturbance, but research is necessary to determine directionality, examine the influence of other factors, and speak to causality.

Many countries adopted comprehensive national initiatives to promote equity in higher education with the goal of transforming the culture of research. Major health research funders are supporting this work through calls for projects that focus on equity, resulting in a proliferation of theoretical frameworks including “intersectionality,” “health equity,” and variations of equity, diversity and inclusion, or EDI. This commentary is geared at individual principal investigators and health research teams who are developing research proposals and want to consider equity issues in their research, perhaps for the first time. We present histories and definitions of three commonly used frameworks: intersectionality, health equity, and EDI. In the context of health research, intersectionality is a methodology (a combination of epistemology and techniques) that can identify the relationships among individual identities and systems of oppression; however, it should also be used internally by research teams to reflect on the production of knowledge. Health equity is a societal goal that operationalizes the social determinants of health to document and address health disparities at the population level. EDI initiatives measure and track progress within organizations or teams and are best suited to inform the infrastructure and human resourcing “behind the scenes” of a project. We encourage researchers to consider these definitions and strive to tangibly move health research towards equity both in the topics we study and in the ways we do research.

Context Ixodes scapularis (the blacklegged tick) is a prominent disease vector that has rapidly expanded across eastern North America in recent decades due to land use and climate change. Predictive modeling is popular for ecological inference and disease management, but few models have considered the multiscale tick and host relationships that drive blacklegged tick expansion. Objectives Predict the probability of occurrence and relative abundance of the blacklegged tick in Ohio, USA at an informative resolution for disease surveillance (800-m 2 ) following CDC guidelines. Determine drivers of tick expansion at the tick and host level through a multiscale analysis of climate, habitat, and host density variables. Methods We modeled blacklegged tick occurrence and abundance using Integrated Nested Laplace Approximation to analyze the relationships of climate, habitat, and host density with field-collected data from 161 sites. We analyzed habitat variables at several spatial scales (800–5000-m 2 ) expecting they would be most influential at scales relevant to white-tailed deer home range size. Results Occurrence and abundance decreased in drier, hotter areas with higher precipitation variability, and increased in heavily forested areas at the spatial scale relevant to deer home range size (1500-m 2 ). Only the abundance model included host density variables, indicating that host densities influence abundance but not occurrence. Conclusions Our spatial projections show a high probability of occurrence and relative abundance throughout Ohio. Multiscale frameworks are vital for understanding the continuously changing distributions and abundances of arthropod disease vectors that rely on hosts for range expansion.

Workplace experience, defined as the evaluation of the work environment and performance, and a characteristic of workplace culture, can influence an employee's work-life balance. Most carer-employees, who combine paid full-time work and informal caregiving responsibilities, struggle to maintain a healthy work-life balance. Caregiver-Friendly Workplace Programs are designed to improve the work experience, and ultimately, the work-life balance of carer-employees. The purpose of this study is to identify changes in workplace culture through the examination of the efficacy of a caregiver-friendly workplace program on workplace experience. First, we identify whether awareness of a caregiver-friendly workplace program directly increases the amount of work support received and, in turn, improves workplace experience. Second, we will examine if significant differences in the amount of work support received translates into an improved workplace experience for carer-employees over time. Two university-wide online surveys were conducted separately; time 1 (T1) during the summer of 2015, and time 2 (T2), in the summer of 2017. In each survey, nearly 7000 employees received the invitation to participate with a response rate ranging 10% (T1) to 12% (T2). Respondents were asked about their sociodemographic characteristics, caregiving responsibilities (if applicable), awareness of caregiver-friendly workplace program, types of work support received, and work experience. Reliability analyses was conducted for three scales: awareness of caregiver-friendly workplace program; work support, and; workplace experience. Proportional T-tests were used to examine the difference amongst the intervention scales over time. Structural equation modeling (SEM), via path analysis, was used to investigate the causal indirect (awareness of caregiver-friendly workplace program to work support to workplace experience) relationship that define the workplace culture. No significant changes in workplace culture were found over time. However, awareness of caregiver-friendly workplace programs is shown to positively impact the amount of support received, which sequentially improves workplace experience, and ultimately workplace culture. This therefore suggests that the implementation of caregiver-friendly workplace programs is potentially effective. Results suggest that amount of support received, and workplace experience would be better reassessed via a longer time period (i.e., 5 yr. window), and improved support for managers and supervisors is needed to supplement relationships with their employees.

Smartphones are often vilified for negatively influencing well-being and contributing to stress. However, these devices may, in fact, be useful in times of stress and, in particular, aid in stress recovery. Mobile apps that deliver evidence-based techniques for stress reduction, such as heart rate variability biofeedback (HRVB) training, hold promise as convenient, accessible, and effective stress-reducing tools. Numerous mobile health apps that may potentially aid in stress recovery are available, but very few have demonstrated that they can influence health-related physiological stress parameters (eg, salivary biomarkers of stress). The ability to recover swiftly from stress and reduce physiological arousal is particularly important for long-term health, and thus, it is imperative that evidence is provided to demonstrate the effectiveness of stress-reducing mobile health apps in this context. The purpose of this research was to investigate the physiological and psychological effects of using a smartphone app for HRVB training following a stressful experience. The efficacy of the gamified Breather component of the Happify mobile health app was examined in an experimental setting. In this study, participants (N=140) underwent a laboratory stressor and were randomly assigned to recover in one of three ways: with no phone present, with a phone present, with the HRBV game. Those in the no phone condition had no access to their phone. Those in the phone present condition had their phone but did not use it. Those in the HRVB game condition used the serious game Breather on the Happify app. Stress recovery was assessed via repeated measures of salivary alpha amylase, cortisol, and self-reported acute stress (on a 1-100 scale). Participants in the HRVB game condition had significantly lower levels of salivary alpha amylase during recovery than participants in the other conditions (F =3.78, P=.03). There were no significant differences among the conditions during recovery for salivary cortisol levels or self-reported stress. These results show that engaging in a brief HRVB training session on a smartphone reduces levels of salivary alpha amylase following a stressful experience, providing preliminary evidence for the effectiveness of Breather in improving physiological stress recovery. Given the known ties between stress recovery and future well-being, this study provides a possible mechanism by which gamified biofeedback apps may lead to better health.