Baicalin alleviates acute lung injury in vivo and in vitro.

The aim of the present study was to evaluate the effects and mechanisms of Baicalin (BA) on acute lung injury (ALI). ALI model was established by lipopolysaccharide (LPS) and proteomics, immunoprecipitation and F-box/WD repeat containing protein 7 （FBXW7） knockout (KO) mice and FBXW7 silence mouse lung epithelial (MLE-12) cells were used to investigate the mechanisms of BA on acute lung injury ALI. The results showed that 218 differentially expressed proteins were identified in the lung tissue of ALI mice and FBXW7 was one of the changed most proteins and was significantly decreased in in the lung tissue of ALI mice. It was also found that FBXW7 had protective effects on ALI via inhibition of Absent in Melanoma 2 （AIM2） inflammasomes also found that BA mitigated ALI via FBXW7/AIM2 signal pathway. In conclusion, FBXW7 as a key marker was identified in ALI and has a protective effect on ALI and BA regulated FBXW7/AIM2 signal pathway to alleviate ALI. This study provided a new method for treating ALI.

National implementation trial of BeUpstanding™: an online initiative for workers to sit less and move more.

BACKGROUND: The online BeUpstanding™ program is an eight-week workplace-delivered intervention for desk-based workers to raise awareness of the benefits of sitting less and moving more and build a supportive culture for change. A workplace representative (the "champion") delivers the program, which includes a workshop where teams collectively choose their sit less/move more strategies. A toolkit provides the champion with a step-by-step guide and associated resources to support program uptake, delivery, and evaluation. Here we report on the main findings from the Australian national implementation trial of BeUpstanding. METHODS: Recruitment (12/06/2019 to 30/09/2021) was supported by five policy and practice partners, with desk-based work teams from across Australia targeted. Effectiveness was measured via a single arm, repeated-measures trial. Data were collected via online surveys, toolkit analytics, and telephone calls with champions. The RE-AIM framework guided evaluation, with adoption/reach (number and characteristics); effectiveness (primary: self-reported workplace sitting time); implementation (completion of core components; costs); and, maintenance intentions reported here. Linear mixed models, correcting for cluster, were used for effectiveness, with reach, adoption, implementation, and maintenance outcomes described. RESULTS: Of the 1640 website users who signed-up to BeUpstanding during the recruitment period, 233 were eligible, 198 (85%) provided preliminary consent, and 118 (50.6%) champions consented and started the trial, with 94% (n = 111 champions) completing. Trial participation was from across Australia and across industries, and reached 2,761 staff, with 2,248 participating in the staff survey(s): 65% female; 64% university educated; 17% from a non-English speaking background. The program effectively changed workplace sitting (-38.5 [95%CI -46.0 to -28.7] minutes/8-hour workday) and all outcomes targeted by BeUpstanding (behaviours and culture), with small-to-moderate statistically-significant effects observed. All participating teams (n = 94) completed at least 5/7 core steps; 72.4% completed all seven. Most champions spent $0 (72%) or >$0-$5 (10%) per team member; most (67/70 96%) intended to continue or repeat the program. CONCLUSIONS: BeUpstanding can be adopted and successfully implemented by a range of workplaces, reach a diversity of staff, and be effective at creating a supportive culture for teams of desk-based workers to sit less and move more. Learnings will inform optimisation of the program for longer-term sustainability. TRIAL REGISTRATION: ACTRN12617000682347.

Silicon dioxide particles induce DNA oxidative damage activating the AIM2-mediated PANoptosis in mice cerebellum.

Silicon dioxide (SiO2) particles are novel materials with wide-ranging applications across various fields, posing potential neurotoxic effects. This study investigates the toxicological mechanisms of SiO2 particles of different sizes on murine cerebellar tissue and cells. Six-week-old C57BL/6 mice were orally administered SiO2 particles of three sizes (1 µm, 300 nm, 50 nm) for 21 days to establish an in vivo model, and mice cerebellar astrocytes (C8-D1A cells) were cultured in vitro. Indicators of oxidative stress, DNA damage, and the PANoptosis pathway were detected using methods such as immunofluorescence staining, comet assay, western blotting, and qRT-PCR. The results show that SiO2 particles induce oxidative stress leading to DNA oxidative damage. The aberrant DNA is recognized by AIM2 (absent in melanoma 2), which activates the assembly of the PANoptosome complex, subsequently triggering PANoptosis. Furthermore, the extent of damage is inversely correlated with the size of SiO2 particles. This study elucidates the toxicological mechanism of SiO2 particles causing cerebellar damage via PANoptosis, extending research on PANoptosis in neurotoxicology, and aiding in the formulation of stricter safety standards and protective measures to reduce the potential toxic risk of SiO2 particles to humans.

The critical elements of digital health in diabetes and cardiometabolic care.

Digital innovations provide novel opportunities to individualize a person's care to best match their lifestyle needs and circumstances and to support them as they live their daily lives with diabetes. These innovations also serve to provide actionable data and insights for the care team giving them a "Webb telescope-like" view into their individual self-management journey, allowing them to see what cannot be seen during infrequent and limited office visits, thereby facilitating collaboration and communication to optimize the care plan on a timely basis. Technology advances are enabling diabetes care to transition from episodic, synchronous, primarily in-person care to include synchronous virtual care options and to continuous, on-demand, data-informed, asynchronous digital care better matching the demands of living with a relentless 24/7 chronic condition. In this paper we will discuss the critical elements and considerations in designing and implementing successful diabetes digital health tools in clinical practice.

Coaching the coaches: exploring the effectiveness of the 'Move Well Be strong' youth injury prevention programme for grassroot coaches and PE teachers.

INTRODUCTION: Coaches play a major role in developing movement in their performers, especially at grassroots levels. However, there are significant knowledge gaps amongst grassroots coaches and physical education (PE) teachers regarding movement competency and injury prevention programs. This study aimed to explore the effectiveness of knowledge gain, adoption and implementation following a youth injury prevention workshop for grassroots coaches and PE teachers. METHODS: 56 grassroots coaches and PE teachers completed a validated questionnaire exploring use, knowledge, attitude towards and confidence to deliver youth movement competency training before and after an online workshop. Bayesian Wilcoxon signed-rank tests were used to assess the knowledge, attitude, and confidence to deliver an injury prevention programme following the workshop. For all the Bayesian inference tests run, the Bayesian factor (BF10) was interpreted using the evidence categories ranging from extreme evidence (BF10 > 100) to anecdotical evidence (BF10 < 1). RESULTS: Post-workshop there was a 34% increase in respondents indicating that they had greater knowledge of injury prevention issues (55% pre-workshop vs 89% post-workshop) with statistically positive and moderate effects (BF10 > 100 [extreme evidence]). There was also a 25% increase in respondents indicating that they had a more sympathetic attitude towards injury prevention (67% sympathetic pre-workshop vs 93% sympathetic post-workshop) with statistically moderate effects (BF10 = 87.4 [very strong evidence]). A 19% increase in attendees' confidence to deliver an injury prevention programme was observed (69% high pre-workshop vs. 89% high post-workshop) with statistically moderate effects (BF10 = 85.9 [very strong evidence]). 100% of participants indicated an intent to adopt the injury prevention programme. CONCLUSIONS: An online workshop increased knowledge and confidence in grassroots coaches and PE teachers to deliver a youth injury prevention programme. Knowledge gained from training and upskilling created a positive attitude and confidence to deliver movement competency into coaching. Appropriate resources need to be developed and delivered in an accessible way to grassroots coaches and PE teachers via workshops and should be included in governing body coaching awards or as continuing professional development for youth coaches and PE teachers.

Deletion of absent in melanoma-2 (AIM2) drives bone marrow adipogenesis and impairs bone microarchitecture.

Absent in melanoma (AIM) 2, a gene induced by interferon, acts as a cytosolic sensor for double-stranded (ds) DNA. It forms the AIM2 inflammasome, producing interleukin (IL)-1ß and IL-18. Our previous study demonstrated that mice lacking AIM2 exhibit spontaneous obesity, insulin resistance, and inflammation in adipose tissue. In this study, we aimed to explore the impact of AIM2 gene deletion on the bone marrow microenvironment and bone morphology in adult and aged mice. Utilizing micro-computed tomography (micro-CT), we discovered that female mice lacking AIM2 showed an increase in the total cross-sectional area at 5 months of age, accompanied by an increase in cortical thickness in the mid-diaphysis of the femur at both 5 and 15 months of age. At 15 months, the cortical bone mineral density (BMD) significantly decreased in AIM2 null females compared to wildtype (WT) mice. Trabecular bone volume and BMD at the distal metaphysis of the femur and the lumbar vertebra-4 were also significantly decreased in AIM2 null females. Histological examination of femurs from aged mice demonstrated increased bone marrow adiposity in AIM2 null mice, accompanied by a significant increase in CD45 - /CD31 - /Sca1 + /Pdgfa + adipogenic progenitor cells and a decrease in the ratio of CD45 - /CD31 - /Sca1 - /Pdgfa + osteogenic progenitor cells, as determined by flow cytometry of bone marrow cells. RNAseq analysis of the bone marrow revealed a significant increase in interferon-stimulated genes with Ifi202b as the top-upregulated gene in AIM2 null mice. Our findings suggest that AIM2 deficiency affects bone health by promoting adipogenesis in the bone marrow and inducing a pro-inflammatory environment, thereby contributing to decreased bone mineral density.

Shared-Care in Complex Malignant Hematology: An Integrative Review Using the RE-AIM Evaluation Framework.

Complex malignant hematology (CMH) shared-care programs have been established to support patients with access to care closer to home. This integrative review examined what is known about CMH shared-care using the RE-AIM evaluation framework. We searched five electronic databases for articles published until 16 January 2024. Articles were included if they were qualitative or quantitative studies, reviews or discussion papers, and reported on an experience with shared-care (defined as a reciprocal, ongoing patient-sharing relationship between a specialist centre and community hospital) for patients with hematological malignancies, and examined one or more aspects of the RE-AIM framework. The search yielded 6523 articles; 10 articles describing eight shared-care experiences. Indicators of reach were reported for 65% of the programs, and emphasized some patient eligibility criteria. Effectiveness indicators were reported for 28% of programs, and suggested favourable survival outcomes within a shared-care model; however, health system impact and quality of life studies were lacking. Indicators of adoption and implementation were reported for 56% and 42% of programs, respectively, and emphasized multidisciplinary teams, infrastructure support, and communication strategies. Maintenance was not reported. Common elements contribute to the implementation of existing CMH shared-care programs; however, a formal evaluation remains an area of need.

Mood regulation in euthymic patients with a history of antidepressant-induced mania.

INTRODUCTION: The use of antidepressants in bipolar disorder (BD) remains contentious, in part due to the risk of antidepressant-induced mania (AIM). However, there is no information on the architecture of mood regulation in patients who have experienced AIM. We compared the architecture of mood regulation in euthymic patients with and without a history of AIM. METHODS: Eighty-four euthymic participants were included. Participants rated their mood, anxiety and energy levels daily using an electronic (e-) visual analog scale, for a mean (SD) of 280.8(151.4) days. We analyzed their multivariate time series by computing each variable's auto-correlation, inter-variable cross-correlation, and composite multiscale entropy of mood, anxiety, and energy. Then, we compared the data features of participants with a history of AIM and those without AIM, using analysis of covariance, controlling for age, sex, and current treatment. RESULTS: Based on 18,103 daily observations, participants with AIM showed significantly stronger day-to-day auto-correlation and cross-correlation for mood, anxiety, and energy than those without AIM. The highest cross-correlation in participants with AIM was between mood and energy within the same day (median (IQR), 0.58 (0.27)). The strongest negative cross-correlation in participants with AIM was between mood and anxiety series within the same day (median (IQR), -0.52 (0.34)). CONCLUSION: Patients with a history of AIM have a different underlying mood architecture compared to those without AIM. Their mood, anxiety and energy stay the same from day-to-day; and their anxiety is negatively correlated with their mood.

Evaluating the implementation of weekly rifapentine-isoniazid (3HP) for tuberculosis prevention among people living with HIV in Uganda: A qualitative evaluation of the 3HP Options Trial.

Three months of isoniazid-rifapentine (3HP) is being scaled up for tuberculosis (TB) preventive treatment (TPT) among people living with HIV (PLHIV) in high-burden settings. More evidence is needed to identify factors influencing successful 3HP delivery. We conducted a qualitative assessment of 3HP delivery nested within the 3HP Options Trial, which compared three optimized strategies for delivering 3HP: facilitated directly observed therapy (DOT), facilitated self-administered therapy (SAT), and patient choice between facilitated DOT and facilitated SAT at the Mulago HIV/AIDS clinic in Kampala, Uganda. We conducted 72 in-depth interviews among PLHIV purposively selected to investigate factors influencing 3HP acceptance and completion. We conducted ten key informant interviews with healthcare providers (HCPs) involved in 3HP delivery to identify facilitators and barriers at the clinic level. We used post-trial 3HP delivery data to assess sustainability. We conducted an inductive thematic analysis and aligned the emergent themes with the RE-AIM framework dimensions to report implementation outcomes. Understanding the need for TPT, once-weekly dosing, shorter duration, and perceived 3HP safety enhanced acceptance overall. Treatment monitoring by HCPs and reduced risk of HIV status disclosure enabled DOT acceptance. Dosing autonomy enabled SAT acceptance. Switching between DOT and SAT as required enabled acceptance for patient choice. Dosing reminders, reimbursement for clinical visits, and social support enabled 3HP completion; pill burden, side effects, and COVID-19-related treatment restrictions hindered completion. All HCPs were trained and participated in 3HP delivery with high fidelity. Training, care integration, and collaboration among HCPs enabled, whereas initial concerns about 3HP safety among HCPs delayed 3HP adoption and implementation. SAT was maintained post-trial; DOT was discontinued due to inadequate ongoing financial support beyond the study period. Facilitated delivery strategies made 3HP treatment convenient for PLHIV and were feasible and implemented with high fidelity by HCPs. However, the costs of 3HP facilitation may limit wider scale-up.

Implementation Evaluation of a Parks- and Faith-Based Multilevel Intervention to Promote Physical Activity Among Latinos.

BACKGROUND: Latinos in the United States face multiple barriers to engaging in physical activity (PA). We implemented a faith-based multilevel intervention to promote PA in parks for Latino adults, which was partially adapted to a virtual platform during the COVID-19 pandemic, and evaluated it using the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. METHODS: We conducted in-depth semistructured interviews (83% in Spanish) with 24 intervention participants (75% women) participating in a cluster randomized controlled trial in 2019-2022 that linked 6 churches (3 intervention, 3 control) with parks in East Los Angeles, CA. The intervention included in-person, park-based fitness classes, which were adapted to Facebook during the pandemic; PA motivational text messages; and other activities. Interviews assessed Reach (participation), Effectiveness (perceived impacts), Implementation (participation barriers/facilitators), and Maintenance (plans for sustaining PA), as well as perceived pandemic impacts. RESULTS: About 80% of interviewees participated in ≥1 park class and 67% in ≥1 virtual class (Reach). Interviewees perceived positive intervention impacts across multiple health and well-being domains (Effectiveness) despite perceived negative pandemic impacts; several facilitators to participation (personal, social, program) and few barriers (personal, virtual, environmental; Implementation); and plans for maintaining PA (eg, revisiting intervention text messages and video recordings; Maintenance). CONCLUSIONS: Findings support the utility of Reach, Effectiveness, Adoption, Implementation, and Maintenance to understand the broad impacts of a faith-based PA intervention. Findings point to the adaptability and robustness of the intervention during a public health crisis. Overall, findings may help inform the translation of the intervention to other communities to advance health equity.

The role of inflammasomes as central inflammatory hubs in Mycobacterium tuberculosis infection.

Mycobacterium tuberculosis (Mtb) infection represents a global health problem and is characterized by formation of granuloma with a necrotic center and a systemic inflammatory response. Inflammasomes have a crucial role in the host immune response towards Mtb. These intracellular multi-protein complexes are assembled in response to pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). Inflammasome platforms activate caspases, leading to the maturation of the proinflammatory cytokines interleukin (IL)-1 and 18 and the cleavage of gasdermin D (GSDMD), a pore-forming protein responsible for cytokine release and pyroptotic cell death. Recent in vitro and in vivo findings have highlighted the importance of inflammasome signaling and subsequent necrotic cell death in Mtb-infected innate immune cells. However, we are just beginning to understand how inflammasomes contribute to disease or to a protective immune response in tuberculosis (TB). A detailed molecular understanding of inflammasome-associated pathomechanisms may foster the development of novel host-directed therapeutics or vaccines with improved activity. In this mini-review, we discuss the regulatory and molecular aspects of inflammasome activation and the associated immunological consequences for Mtb pathogenesis.

EIF2AK2 protein targeted activation of AIM2-mediated PANoptosis promotes sepsis-induced acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) frequently occurs as a complication of sepsis. PANoptosis refers to a type of inflammatory programmed cell death that exhibits key characteristics of apoptosis, necroptosis, and pyroptosis. Here, we evaluated the role of absent in melanoma 2 (AIM2) and eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2) in septic AKI. METHODS: A septic AKI model was created through cecal ligation and puncture (CLP), while an in vitro model was developed using lipopolysaccharide (LPS)-stimulated HK2 cells. Hematoxylin and eosin (HE), Periodic acid-Schiff (PAS), and TUNEL staining were conducted to assess kidney injury in mice. Levels of serum creatinine (Scr) and blood urea nitrogen (BUN) were detected by kits. Gene expression was detected utilizing RT-qPCR, and Western blot was used to test protein levels. Immunofluorescence was employed to measure EIF2AK2 and AIM2 expression in mouse kidney tissue. Lactate dehydrogenase (LDH) activity assay was conducted to evaluate cytotoxicity. Co-immunoprecipitation (Co-IP) was performed to verify the binding relationship between EIF2AK2 and AIM2. RESULTS: AIM2 expression was increased in the renal tissue of mice subjected to CLP. Activation of the inflammasome and PANoptosis were observed in the renal tissue of CLP mice. AIM2 depletion attenuated PANoptosis in LPS-treated HK-2 cells. Additionally, EIF2AK2 could directly target AIM2, leading to a positive regulation of AIM2 expression. Notably, EIF2AK2 induced PANoptosis through upregulating AIM2 in HK-2 cells stimulated by LPS. CONCLUSIONS: Our results revealed the important role of EIF2AK2-induced AIM2 upregulation in the activation of PANoptosis during septic AKI.

Renal tissue from CLP mice exhibited an increase in AIM2 expression.Renal tissue from CLP mice demonstrated inflammasome activation and PANoptosis.AIM2 silencing reduced PANoptosis in LPS-treated HK-2 cells.EIF2AK2 directly targeted AIM2 and positively regulated its expression.EIF2AK2 promoted PANoptosis via AIM2 in LPS-triggered HK-2 cells.

AIM2 Deficiency Alleviates Cardiac Inflammation and Hypertrophy in HFD/STZ-Induced Diabetic Mice by Inhibiting the NLRC4/IRF1 Signaling Pathway.

Absent in melanoma 2(AIM2) exacerbates atherosclerosis by inflammasome assembly. However, AIM2-mediated inflammation in diabetic cardiomyopathy remains incompletely understood. Here we investigate the role of AIM2 in high glucose (HG)- and diabetes-induced inflammatory cardiomyopathy. By RNA-seq, we found that AIM2 were significantly upregulated in HG-induced macrophages, upregulation of AIM2 in cardiac infiltrating macrophages was confirmed in a high-fat diet (HFD)/streptozotocin (STZ)-induceddiabetic mouse model . Therefore, AIM2 knockout mice were constructed. Compared to WT mice, HFD/STZ-induced cardiac hypertrophy and dysfunction were significantly improved in AIM2-/- mice, despite no changes in blood glucose and body weight. Further, AIM2 deficiency inhibited cardiac recruitment of M1-macrophages and cytokine production. Mechanistically, AIM2-deficient macrophgaes reduced IL-1ß and TNF-α secretion, which impaired the NLRC4/IRF1 signaling in cardiomyocytes, and reduced further recruitment of macrophages, attenuated cardiac inflammation and hypertrophy, these effects were confirmed by silencing IRF1 in WT mice, and significantly reversed by overexpression of IRF1 in AIM2-/- mice. Taken together, our findings suggest that AIM2 serves as a novel target for the treatment of diabetic cardiomyopathy.

Tracking implementation strategies in real-world settings: VA Office of Rural Health enterprise-wide initiative portfolio.

OBJECTIVE: To use a practical approach to examining the use of Expert Recommendations for Implementing Change (ERIC) strategies by Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) dimensions for rural health innovations using annual reports on a diverse array of initiatives. DATA SOURCES AND STUDY SETTING: The Veterans Affairs (VA) Office of Rural Health (ORH) funds initiatives designed to support the implementation and spread of innovations and evidence-based programs and practices to improve the health of rural Veterans. This study draws on the annual evaluation reports submitted for fiscal years 2020-2022 from 30 of these enterprise-wide initiatives (EWIs). STUDY DESIGN: Content analysis was guided by the RE-AIM framework conducted by the Center for the Evaluation of Enterprise-Wide Initiatives (CEEWI), a Quality Enhancement Research Initiative (QUERI)-ORH partnered evaluation initiative. DATA COLLECTION AND EXTRACTION METHODS: CEEWI analysts conducted a content analysis of EWI annual evaluation reports submitted to ORH. Analysis included cataloguing reported implementation strategies by Reach, Adoption, Implementation, and Maintenance (RE-AIM) dimensions (i.e., identifying strategies that were used to support each dimension) and labeling strategies using ERIC taxonomy. Descriptive statistics were conducted to summarize data. PRINCIPAL FINDINGS: A total of 875 implementation strategies were catalogued in 73 reports. Across these strategies, 66 unique ERIC strategies were reported. EWIs applied an average of 12 implementation strategies (range 3-22). The top three ERIC clusters across all 3 years were Develop stakeholder relationships (21%), Use evaluative/iterative strategies (20%), and Train/educate stakeholders (19%). Most strategies were reported within the Implementation dimension. Strategy use among EWIs meeting the rurality benchmark were also compared. CONCLUSIONS: Combining the dimensions from the RE-AIM framework and the ERIC strategies allows for understanding the use of implementation strategies across each RE-AIM dimension. This analysis will support ORH efforts to spread and sustain rural health innovations and evidence-based programs and practices through targeted implementation strategies.

The development and evaluation of the Designing for Dissemination and Implementation Learning Hub.

There is a growing emphasis on reducing the gap between research and routine practice. Dissemination and Implementation (D&I) science offers theories, models, and frameworks to enhance the implementation, impact, and sustainment of new programs and interventions. Few training opportunities are available that help leaders, researchers, clinicians, and staff (implementers) translate original research into practice settings in a more timely and effective manner without requiring significant time away from their primary clinical duties. To address these needs, we designed a virtual Designing for Dissemination and Implementation (D4D&I) Learning Hub that offered foundational D&I knowledge and opportunities for skill building. We developed the D4D&I Learning Hub curricula to train novice participants in the multicomponent D4D&I implementation strategy bundle when implementing new programs or innovations. The components of the D4D&I strategy bundle include (i) Pre-implementation assessment for proactive planning and multilevel contextual assessment, (ii) Multilevel partner engagement to learn what is important to end-users and obtain buy-in, (iii) Implementation and adaptations guided by a pre-implementation assessment while retaining program fidelity, and (iv) Program evaluation. We utilized a virtual e-learning platform, expert trainers, mentorship, and a Virtual Learning Collaborative to deliver the six-module curricula to support participants' growth and success. We used quantitative and qualitative methods informed by the Kirkpatrick Evaluation Model to evaluate the D4D&I Learning Hub. Thirty-one participants completed the D4D&I Learning Hub across four cohorts. Participants found the D4D&I curricula relevant and favorable, indicating they acquired the intended knowledge and skills. In presentations of their key takeaways, participants cited a greater understanding of how to apply various D&I theories, models, and frameworks to their research, engage multilevel partners during all phases of implementation and evaluation, and assess fidelity and adaptations. Participants planned to incorporate the acquired D&I knowledge and skills in future publications, grant applications, and when implementing new programs and projects in clinical settings. The D4D&I Learning Hub provides foundational education for novice participants of D&I science. It promotes designing, disseminating, implementing, and evaluating effective programs in clinical settings. This article discusses the development and implementation of the D4D&I Learning Hub. In addition, we evaluated the first four cohorts using the Kirkpatrick Evaluation Model.

This article describes the design, delivery, and evaluation of an online educational course about the multicomponent Designing for Dissemination and Implementation strategy bundle to mitigate barriers when implementing new programs in real-world settings. This is important because many healthcare programs often never reach patients due to a lack of training for researchers and clinicians. This online Learning Hub provides an opportunity for healthcare leaders, researchers, clinicians, and staff to gain D&I knowledge, and practice skills that will help them offer new innovations in healthcare to patients. Further benefits of this Learning Hub are the emphasis on learning the foundations of D&I, practicing skills together, and creating healthcare partners who can work together to improve healthcare for patients.

A detailed TD-DFT and intermolecular interaction study of vitamin K in soluble, poorly soluble and insoluble solvents, as well as an ADME and molecular docking study.

Vitamin K is one of the most important fat-soluble vitamins and while there are two main types of vitamin K in nature, known as K1 (phylloquinone) and K2 (menaquinones), there is also a synthetic type of vitamin K known as K3 (menadione). Recent studies have shown that it is crucial to know the non-covalent interactions, ADME and molecular docking of molecules in different solvent media. Therefore, we have performed some quantum chemical calculations, ADME and intra-and intermolecular interaction calculations of a number of K1, K2 and K3 such as K1-water (K1 + W), K1-methanol (K1 + M), K1-triacetin (K1 + T), K2-water (K2 + W), K2-methanol (K2 + M), K2-triacetin (K2 + T), K3-water (K3 + W), K3-methanol (K3 + M), K3-triacetin (K3 + T) performed by Density Functional Theory (DFT) and Multiwfn: A multifunctional wavefunction analyzer. Molecular structures, HOMO-LUMO energies, MEP and electronic properties have been calculated and described using DFT at the level of B3LYP/6-311G (d,p) level. The nature of the molecular interactions between vitamin K and solvents such as water, methanol and triacetin were also investigated using topological analyses such as atoms in molecule (AIM), non-covalent interaction index (NCI), reduced density gradient (RDG), Localized orbital locator (LOL) and electron localization function (ELF). In addition, FMO for electronic transitions, MEP for electrophilic and nucleophilic attack, ADME to investigate how a chemical is processed by a living organism, and Fukui functions to determine electron density are explained. Finally, molecular docking was used to determine the biological activity of the vitamin K.

Innovate! Accelerate! Evaluate! Harnessing the RE-AIM framework to examine the global dissemination of parenting resources during COVID-19 to more than 210 million people.

BACKGROUND: Parents were at the forefront of responding to the needs of children during the COVID-19 pandemic. This study used the RE-AIM framework to examine the Reach, Effectiveness, Adoption, Implementation, and Maintenance of a global inter-agency initiative that adapted evidence-based parenting programs to provide immediate support to parents. METHODS: Data were collected via short surveys sent via email, online surveys, and analysis of social media metrics and Google Analytics. Retrospective surveys with 1,303 parents and caregivers in 11 countries examined impacts of the resources on child maltreatment, positive relationship building, parenting efficacy, and parenting stress. RESULTS: The parenting resources were translated into over 135 languages and dialects; reached an estimated minimum 212.4 million people by June 2022; were adopted by 697 agencies, organizations, and individuals; and were included in 43 national government COVID-19 responses. Dissemination via social media had the highest reach (n = 144,202,170, 67.9%), followed by radio broadcasts (n = 32,298,525, 15.2%), text messages (n = 13,565,780, 6.4%), and caseworker phone calls or visits (n = 8,074,787, 3.8%). Retrospective surveys showed increased parental engagement and play, parenting self-efficacy, confidence in protecting children from sexual abuse, and capacity to cope with stress, as well as decreased physical and emotional abuse. Forty-four organizations who responded to follow-up surveys in April 2021 reported sustained use of the resources as part of existing services and other crisis responses. CONCLUSION: This study highlights the importance of a) establishing an international collaboration to rapidly adapt and disseminate evidence-based content into easily accessible resources that are relevant to the needs of parents; b) creating open-source and agile delivery models that are responsive to local contexts and receptive to further adaptation; and c) using the best methods available to evaluate a rapidly deployed global emergency response in real-time. Further research is recommended to empirically establish the evidence of effectiveness and maintenance of these parenting innovations.

Evaluation of implementation of evidence-based public health training in sub-Saharan Africa.

Background: The Collaboration for Evidence-based Healthcare and Public Health in Africa (CEBHA+) developed and offered a course on evidence-based public health (EBPH) in five sub-Saharan African (SSA) countries to enhance individual and institutional capacity. Aim: This study aims to assess, compare and learn from implementing the CEBHA+ EBPH course using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework and Practical, Robust, Implementation and Sustainability Model (PRISM). Setting: This study involved CEHBA+ partner universities in five countries in SSA. Methods: We developed a framework that draws on signalling questions for RE-AIM and PRISM dimensions. Country teams reflected on, discussed and mapped unique experiences. Using this framework, we then elicited common themes across countries and distilled country-specific experiences through virtual discussions. Results: Across countries, 130 public health practitioners, researchers and students completed the course (Reach). The course increased EBPH knowledge and skills and the capacity to teach EBPH and resulted in immediate opportunities for applying skills (Effectiveness). Hybrid offering in two countries presented challenges regarding Internet connectivity and hybrid discussions. Facilitators had previous training in teaching EBPH. While learning material was the same across countries, the content was adapted to represent local public health priorities (Implementation, Adoption). Course materials have informed other related training leading to spin-offs (Maintenance). Institutionalisation is dependent on external funding. Conclusion: Strengthening EBPH capacity across contexts is feasible. Curricula containing both core and contextualised elements create an authentic learning environment. Formal evaluations should be embedded within capacity-strengthening initiatives. Contribution: This is the first study evaluating EBPH training in SSA using an implementation science lens, offering learning about context-relevant adaptations that assist with plans for sustainability and scale.

Effects and implementation of an intervention to improve sleep, fatigue and recovery among healthcare workers with night shifts: A pre- and post-test study.

BACKGROUND: Previous intervention studies among night workers mainly focused on single interventions and found inconclusive evidence for effectiveness. A comprehensive intervention approach that includes individual and environmental components has been argued as important. Gaining insight into contributing factors for the implementation of interventions for night workers and effectiveness is important to distinguish between theory and programme failure. OBJECTIVES: To evaluate the effects and implementation of the PerfectFit@Night intervention to improve sleep, fatigue and recovery of night workers in healthcare, using the RE-AIM framework, which assesses reach, effectiveness, adoption, implementation and maintenance of interventions. DESIGN: A prospective pre-post study design, with two measurements before and three and six months after the intervention. SETTING: Twelve different departments of a university hospital in the Netherlands. PARTICIPANTS: Healthcare workers working night shifts (n = 210). METHODS: PerfectFit@Night consisted of environmental (provision of a powernap bed and healthy food, and workshop healthy rostering) and individual elements (e-learning and sleep coaching) and was implemented for three months in a phased manner. Questionnaires, logbooks and interview data were used. Effects of the intervention on sleep, fatigue and recovery were evaluated with mixed-effects models, and implementation factors of reach, adoption, implementation and maintenance were evaluated. RESULTS: Night shift-related insomnia (-11 %-points, 95 % CI: -19 %, -4 % at three months), need for recovery (ß: -2.45, 95 % CI: -4.86, -0.03 at six months) and fatigue (OR: 0.46, 95 % CI: 0.25, 0.86 at six months) decreased significantly after the intervention. No changes were found for subjective sleep quality and sleep duration. Barriers and facilitators for implementation were identified for each intervention element at individual (e.g., dietary preferences), organisational (e.g., responsibilities at work) and workplace levels (e.g., location of power nap bed), and for the intervention itself (e.g., useful information in e-learning). Although satisfaction was high and continuation was preferred, embedding of the intervention in the daily routine was limited. Facilitators for future implementation include a positive attitude towards the intervention, clear guidelines regarding intervention elements, appointment of night workers as ambassadors, and suitable conditions in terms of work demands and for the intervention elements. CONCLUSIONS: The multi-faceted PerfectFit@Night intervention reduced insomnia, fatigue and need for recovery in night workers in healthcare. The most important facilitators to improve the implementation of PerfectFit@Night exist at the organisational level (e.g., positive attitude within the culture and suitable work demands). Combining effect and implementation evaluation is crucial to identify barriers and facilitators that hamper or enhance intervention effects. TRIAL REGISTRATION: The study was registered in the Netherlands Trial Register on 17 January 2021 (trial number NL9224).

Genetic and epigenetic regulation of inflammasomes: Role in atherosclerosis.

The cardiovascular complications of atherosclerosis are thought to arise from an inflammatory response to the accumulation of cholesterol-rich lipoproteins in the arterial wall. The positive outcome of CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) provided key evidence to support this concept and suggested that inflammasomes and IL-1ß are important inflammatory mediators in human atherosclerotic cardiovascular diseases (ACVD). In specific settings NLRP3 or AIM2 inflammasomes can induce inflammatory responses in the arterial wall and promote the formation of unstable atherosclerotic plaques. Clonal hematopoiesis (CH) has recently emerged as a major independent risk factor for ACVD. CH mutations arise during ageing and commonly involves variants in genes mediating epigenetic modifications (TET2, DNMT3A, ASXL1) or cytokine signaling (JAK2). Accumulating evidence points to the role of inflammasomes in the progression of CH-induced ACVD events and has shed light on the regulatory pathways and possible therapeutic approaches that specifically target inflammasomes in atherosclerosis. Epigenetic dynamics play a vital role in regulating the generation and activation of inflammasome components by causing changes in DNA methylation patterns and chromatin assembly. This review examines the genetic and epigenetic regulation of inflammasomes, the intersection of macrophage cholesterol accumulation with inflammasome activation and their roles in atherosclerosis. Understanding the involvement of inflammasomes in atherosclerosis pathogenesis may lead to customized treatments that reduce the burden of ACVD.