Implementing Trauma-Informed Care-Settings, Definitions, Interventions, Measures, and Implementation across Settings: A Scoping Review.

Traumatic experiences can have long-lasting negative effects on individuals, organizations, and societies. If trauma is not addressed, it can create unsafe cultures with constant arousal, untrusting relationships, and the use of coercive measures. Trauma-informed care (TIC) can play a central role in mitigating these negative consequences, but it is unknown how and in which way(s) TIC should be implemented. Our objective was to conduct a scoping review that systematically explored and mapped research conducted in this area and to identify existing knowledge about the implementation of TIC. The search was conducted on the CINAHL, Cochrane, Embase, ERIC, Medline, PsycINFO, and Web of Science databases, and more than 3000 empirical papers, published between 2000 and 2022, were identified. Following further screening, we included 157 papers in our review, which were mainly from the USA, Australia, New Zealand, and Canada, focusing on study settings, methodologies, and definitions of TIC, as well as the types of interventions and measures used. This review shows that TIC is a complex and multifaceted framework, with no overarching structure or clear theoretical underpinnings that can guide practical implementations. TIC has been defined and adapted in varied ways across different settings and populations, making it difficult to synthesize knowledge. A higher level of agreement on how to operationalize and implement TIC in international research could be important in order to better examine its impact and broaden the approach.

Ontology-based modeling, integration, and analysis of heterogeneous clinical, pathological, and molecular kidney data for precision medicine.

Many data resources generate, process, store, or provide kidney related molecular, pathological, and clinical data. Reference ontologies offer an opportunity to support knowledge and data integration. The Kidney Precision Medicine Project (KPMP) team contributed to the representation and addition of 329 kidney phenotype terms to the Human Phenotype Ontology (HPO), and identified many subcategories of acute kidney injury (AKI) or chronic kidney disease (CKD). The Kidney Tissue Atlas Ontology (KTAO) imports and integrates kidney-related terms from existing ontologies (e.g., HPO, CL, and Uberon) and represents 259 kidney-related biomarkers. We also developed a precision medicine metadata ontology (PMMO) to integrate 50 variables from KPMP and CZ CellxGene data resources and applied PMMO for integrative kidney data analysis. The gene expression profiles of kidney gene biomarkers were specifically analyzed under healthy control or AKI/CKD disease statuses. This work demonstrates how ontology-based approaches support multi-domain data and knowledge integration in precision medicine.

Student and teacher performance during COVID-19 lockdown: An investigation of associated features and complex interactions using multiple data sources.

Due to the COVID-19 pandemic, testing what is required to support teachers and students while subject to forced online teaching and learning is relevant in terms of similar situations in the future. To understand the complex relationships of numerous factors with teaching during the lockdown, we used administrative data and survey data from a large Danish university. The analysis employed scores from student evaluations of teaching and the students' final grades during the first wave of the COVID-19 lockdown in the spring of 2020 as dependent targets in a linear regression model and a random forest model. This led to the identification of linear and non-linear relationships, as well as feature importance and interactions for the two targets. In particular, we found that many factors, such as the age of teachers and their time use, were associated with the scores in student evaluations of teaching and student grades, and that other features, including peer interaction among teachers and student gender, also exerted influence, especially on grades. Finally, we found that for non-linear features, in terms of the age of teachers and students, the average values led to the highest response values for scores in student evaluations of teaching and grades.

A spatially specified systems pharmacology therapy for axonal recovery after injury.

There are no known drugs or drug combinations that promote substantial central nervous system axonal regeneration after injury. We used systems pharmacology approaches to model pathways underlying axonal growth and identify a four-drug combination that regulates multiple subcellular processes in the cell body and axons using the optic nerve crush model in rats. We intravitreally injected agonists HU-210 (cannabinoid receptor-1) and IL-6 (interleukin 6 receptor) to stimulate retinal ganglion cells for axonal growth. We applied, in gel foam at the site of nerve injury, Taxol to stabilize growing microtubules, and activated protein C to clear the debris field since computational models predicted that this drug combination regulating two subcellular processes at the growth cone produces synergistic growth. Physiologically, drug treatment restored or preserved pattern electroretinograms and some of the animals had detectable visual evoked potentials in the brain and behavioral optokinetic responses. Morphology experiments show that the four-drug combination protects axons or promotes axonal regrowth to the optic chiasm and beyond. We conclude that spatially targeted drug treatment is therapeutically relevant and can restore limited functional recovery.

Spinal cord injury regulates circular RNA expression in axons.

Introduction: Neurons transport mRNA and translational machinery to axons for local translation. After spinal cord injury (SCI), de novo translation is assumed to enable neurorepair. Knowledge of the identity of axonal mRNAs that participate in neurorepair after SCI is limited. We sought to identify and understand how axonal RNAs play a role in axonal regeneration. Methods: We obtained preparations enriched in axonal mRNAs from control and SCI rats by digesting spinal cord tissue with cold-active protease (CAP). The digested samples were then centrifuged to obtain a supernatant that was used to identify mRNA expression. We identified differentially expressed genes (DEGS) after SCI and mapped them to various biological processes. We validated the DEGs by RT-qPCR and RNA-scope. Results: The supernatant fraction was highly enriched for mRNA from axons. Using Gene Ontology, the second most significant pathway for all DEGs was axonogenesis. Among the DEGs was Rims2, which is predominately a circular RNA (circRNA) in the CNS. We show that Rims2 RNA within spinal cord axons is circular. We found an additional 200 putative circRNAs in the axonal-enriched fraction. Knockdown in primary rat cortical neurons of the RNA editing enzyme ADAR1, which inhibits formation of circRNAs, significantly increased axonal outgrowth and increased the expression of circRims2. Using Rims2 as a prototype we used Circular RNA Interactome to predict miRNAs that bind to circRims2 also bind to the 3'UTR of GAP-43, PTEN or CREB1, all known regulators of axonal outgrowth. Axonally-translated GAP-43 supports axonal elongation and we detect GAP-43 mRNA in the rat axons by RNAscope. Discussion: By enriching for axonal RNA, we detect SCI induced DEGs, including circRNA such as Rims2. Ablation of ADAR1, the enzyme that regulates circRNA formation, promotes axonal outgrowth of cortical neurons. We developed a pathway model using Circular RNA Interactome that indicates that Rims2 through miRNAs can regulate the axonal translation GAP-43 to regulate axonal regeneration. We conclude that axonal regulatory pathways will play a role in neurorepair.

Barriers and facilitators for sustainable weight loss in the pre-conception period among Danish women with overweight or obesity - a qualitative study.

BACKGROUND: The prevalence of overweight or obesity in women of reproductive age continues to increase. A high pre-pregnancy body mass index (BMI) has been shown to increase the risk of pregnancy complications and predispose offspring to childhood obesity. However, little is known about factors affecting women's ability to achieve sustainable weight management and very few studies have applied behavior change theory to qualitative data. AIM: This study aimed to explore barriers and facilitators for weight management among women with overweight or obesity, who wanted to lose weight before pregnancy. METHODS: We conducted semi-structured interviews with 17 women with a BMI ≥ 27 kg/m2, who planned to become pregnant in the near future. Data were analyzed using an abductive approach and the Capability, Opportunity, Motivation, and Behavior model was applied as a conceptual framework. RESULTS: The women's strongest motivator for pre-conception weight loss was their ability to become pregnant. Barriers to successful weight management included their partners' unhealthy behaviors, mental health challenges, competing priorities, and internalized weight stigmatization. The women described careful planning, partners' health behaviors, social support, and good mental health as facilitators for sustainable weight management. CONCLUSION: Our study provides insights into factors affecting weight management among women with overweight or obesity in the pre-conception period. Future interventions on weight management require a holistic approach, including a focus on social support, especially from the partner, and mental health, as well as an effort to limit internalized weight stigma.

Synaptojanin 1 Modulates Functional Recovery After Incomplete Spinal Cord Injury in Male Apolipoprotein E Epsilon 4 Mice.

Apolipoprotein E epsilon 4 (ApoE4) is the second most common variant of ApoE, being present in ∼14% of the population. Clinical reports identify ApoE4 as a genetic risk factor for poor outcomes after traumatic spinal cord injury (SCI) and spinal cord diseases such as cervical myelopathy. To date, there is no intervention to promote recovery of function after SCI/spinal cord diseases that is specifically targeted at ApoE4-associated impairment. Studies in the human and mouse brain link ApoE4 to elevated levels of synaptojanin 1 (synj1), a lipid phosphatase that degrades phosphoinositol 4,5-bisphosphate (PIP2) into inositol 4-monophosphate. Synj1 regulates rearrangements of the cytoskeleton as well as endocytosis and trafficking of synaptic vesicles. We report here that, as compared to ApoE3 mice, levels of synj1 messenger RNA and protein were elevated in spinal cords of healthy ApoE4 mice associated with lower PIP2 levels. Using a moderate-severity model of contusion SCI in mice, we found that genetic reduction of synj1 improved locomotor function recovery at 14 days after SCI in ApoE4 mice without altering spared white matter. Genetic reduction of synj1 did not alter locomotor recovery of ApoE3 mice after SCI. Bulk RNA sequencing revealed that at 14 days after SCI in ApoE4 mice, genetic reduction of synj1 upregulated genes involved in glutaminergic synaptic transmission just above and below the lesion. Overall, our findings provide evidence for a link between synj1 to poor outcomes after SCI in ApoE4 mice, up to 14 days post-injury, through mechanisms that may involve the function of excitatory glutaminergic neurons.

Endogenous adenine mediates kidney injury in diabetic models and predicts diabetic kidney disease in patients.

Diabetic kidney disease (DKD) can lead to end-stage kidney disease (ESKD) and mortality; however, few mechanistic biomarkers are available for high-risk patients, especially those without macroalbuminuria. Urine from participants with diabetes from the Chronic Renal Insufficiency Cohort (CRIC) study, the Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes (SMART2D), and the American Indian Study determined whether urine adenine/creatinine ratio (UAdCR) could be a mechanistic biomarker for ESKD. ESKD and mortality were associated with the highest UAdCR tertile in the CRIC study and SMART2D. ESKD was associated with the highest UAdCR tertile in patients without macroalbuminuria in the CRIC study, SMART2D, and the American Indian study. Empagliflozin lowered UAdCR in nonmacroalbuminuric participants. Spatial metabolomics localized adenine to kidney pathology, and single-cell transcriptomics identified ribonucleoprotein biogenesis as a top pathway in proximal tubules of patients without macroalbuminuria, implicating mTOR. Adenine stimulated matrix in tubular cells via mTOR and stimulated mTOR in mouse kidneys. A specific inhibitor of adenine production was found to reduce kidney hypertrophy and kidney injury in diabetic mice. We propose that endogenous adenine may be a causative factor in DKD.

Role of endogenous adenine in kidney failure and mortality with diabetes.

Diabetic kidney disease (DKD) can lead to end-stage kidney disease (ESKD) and mortality, however, few mechanistic biomarkers are available for high risk patients, especially those without macroalbuminuria. Urine from participants with diabetes from Chronic Renal Insufficiency Cohort (CRIC), Singapore Study of Macro-Angiopathy and Reactivity in Type 2 Diabetes (SMART2D), and the Pima Indian Study determined if urine adenine/creatinine ratio (UAdCR) could be a mechanistic biomarker for ESKD. ESKD and mortality were associated with the highest UAdCR tertile in CRIC (HR 1.57, 1.18, 2.10) and SMART2D (HR 1.77, 1.00, 3.12). ESKD was associated with the highest UAdCR tertile in patients without macroalbuminuria in CRIC (HR 2.36, 1.26, 4.39), SMART2D (HR 2.39, 1.08, 5.29), and Pima Indian study (HR 4.57, CI 1.37-13.34). Empagliflozin lowered UAdCR in non-macroalbuminuric participants. Spatial metabolomics localized adenine to kidney pathology and transcriptomics identified ribonucleoprotein biogenesis as a top pathway in proximal tubules of patients without macroalbuminuria, implicating mammalian target of rapamycin (mTOR). Adenine stimulated matrix in tubular cells via mTOR and stimulated mTOR in mouse kidneys. A specific inhibitor of adenine production was found to reduce kidney hypertrophy and kidney injury in diabetic mice. We propose that endogenous adenine may be a causative factor in DKD.

Boldine modulates glial transcription and functional recovery in a murine model of contusion spinal cord injury.

Membrane channels such as those formed by connexins (Cx) and P2X7 receptors (P2X7R) are permeable to calcium ions and other small molecules such as adenosine triphosphate (ATP) and glutamate. Release of ATP and glutamate through these channels is a key mechanism driving tissue response to traumas such as spinal cord injury (SCI). Boldine, an alkaloid isolated from the Chilean boldo tree, blocks both Cx and Panx1 hemichannels (HCs). To test if boldine could improve function after SCI, boldine or vehicle was administered to treat mice with a moderate severity contusion-induced SCI. Boldine led to greater spared white matter and increased locomotor function as determined by the Basso Mouse Scale and horizontal ladder rung walk tests. Boldine treatment reduced immunostaining for markers of activated microglia (Iba1) and astrocytic (GFAP) markers while increasing that for axon growth and neuroplasticity (GAP-43). Cell culture studies demonstrated that boldine blocked glial HC, specifically Cx26 and Cx30, in cultured astrocytes and blocked calcium entry through activated P2X7R. RT-qPCR studies showed that boldine treatment reduced expression of the chemokine Ccl2, cytokine IL-6 and microglial gene CD68, while increasing expression of the neurotransmission genes Snap25 and Grin2b, and Gap-43. Bulk RNA sequencing revealed that boldine modulated a large number of genes involved in neurotransmission in spinal cord tissue just caudal from the lesion epicenter at 14 days after SCI. Numbers of genes regulated by boldine was much lower at 28 days after injury. These results indicate that boldine treatment ameliorates injury and spares tissue to increase locomotor function.

Childhood social capital and drug use disorder in adulthood: A retrospective study on antecedent determinants of the type of drug use.

Based on a sample of Danish adults who were enroled in treatment for drug use disorders as a prerequisite for qualifying for receiving unemployment benefits, we analyse the relationship between low social capital in childhood (LSCC) and the type of drug use in adulthood. The type of drug use is measured by distinguishing between those who were treated for using hard drugs (e.g., heroin and cocaine) and those who were treated for using soft drugs (cannabis). Extracting data from the initial treatment registration report, social capital is operationalised into seven different LSCC categories, and the total number of LSCC (the LSCC score) is recorded. Based on logistic regressions, the LSCC score shows a strong graded dose-response relationship with hard drug use. With each additional LSCC, the probability of being treated for hard drug use increases with 9%. Parental child abuse is the most important single predictor of being treated for hard drug use. Having been parentally abused as a child raises the probability by 32%. The results hold after controlling for age, initiation age, and number of years of drug use, all of which show a significant reversed U-shaped relationship with hard drug use.

Social determinants of visceral leishmaniasis elimination in Eastern Africa.

Visceral leishmaniasis is a vector-borne, protozoan disease with severe public health implications. Following the successful implementation of an elimination programme in South Asia, there is now a concerted endeavour to replicate these efforts in Eastern Africa based on the five essential elimination pillars of case management, integrated vector management, effective surveillance, social mobilisation and operational research. This article highlights how key social determinants (SD) of health (poverty, sociocultural factors and gender, housing and clustering, migration and the healthcare system) operate at five different levels (socioeconomic context and position, differential exposure, differential vulnerability, differential outcomes and differential consequences). These SD should be considered within the context of increasing the success of the five-pillar elimination programme and reducing inequity in health.

A conceptual framework for selecting appropriate populations for public health interventions.

This article suggests a conceptual framework for choice of target populations for public health interventions. In short, who should benefit? Taking the seminal work of Geoffrey Rose on "individuals at risk" versus the "whole population approach" as a point of departure, we explore later contributions. Frohlich and Potvin introduced the notion of "vulnerable populations" applying relevant social determinants as the defining selection criterion. Other interventions focus on a "physical space" (spatial demarcations) such as a neighborhood as a means to define intervention populations. As an addition to these criteria, we suggest that the life-course perspective entails an alternative means of selecting target populations based on a "temporal" perspective. A focus on the various age phases ranging from fetal life and infancy to old age may guide selection of population segments for targeted public health interventions. Each of the selection criteria has advantages and disadvantages when used for primary, secondary, or tertiary prevention. Thus, the conceptual framework may guide informed decisions in public health planning and research regarding precision prevention versus various approaches to complex community-based interventions.

Dissecting aortic aneurysm in Marfan syndrome is associated with losartan-sensitive transcriptomic modulation of aortic cells.

To improve our limited understanding of the pathogenesis of thoracic aortic aneurysm (TAA) that leads to acute aortic dissection, single-cell RNA sequencing (scRNA-seq) was employed to profile disease-relevant transcriptomic changes of aortic cell populations in a well-characterized mouse model of the most commonly diagnosed form of Marfan syndrome (MFS). As result, 2 discrete subpopulations of aortic cells (SMC3 and EC4) were identified only in the aorta of Fbn1mgR/mgR mice. SMC3 cells highly express genes related to extracellular matrix formation and nitric oxide signaling, whereas the EC4 transcriptional profile is enriched in smooth muscle cell (SMC), fibroblast, and immune cell-related genes. Trajectory analysis predicted close phenotypic modulation between SMC3 and EC4, which were therefore analyzed together as a discrete MFS-modulated (MFSmod) subpopulation. In situ hybridization of diagnostic transcripts located MFSmod cells at the intima of Fbn1mgR/mgR aortas. Reference-based data set integration revealed transcriptomic similarity between MFSmod- and SMC-derived cell clusters modulated in human TAA. Consistent with the angiotensin II type I receptor (At1r) contribution to TAA development, MFSmod cells were absent in the aorta of Fbn1mgR/mgR mice treated with the At1r antagonist losartan. Altogether, our findings indicate that a discrete dynamic alteration of aortic cell identity is associated with dissecting TAA in MFS mice and increased risk of aortic dissection in MFS patients.

FN (Fibronectin)-Integrin α5 Signaling Promotes Thoracic Aortic Aneurysm in a Mouse Model of Marfan Syndrome.

BACKGROUND: Marfan syndrome, caused by mutations in the gene for fibrillin-1, leads to thoracic aortic aneurysms (TAAs). Phenotypic modulation of vascular smooth muscle cells (SMCs) and ECM (extracellular matrix) remodeling are characteristic of both nonsyndromic and Marfan aneurysms. The ECM protein FN (fibronectin) is elevated in the tunica media of TAAs and amplifies inflammatory signaling in endothelial and SMCs through its main receptor, integrin α5ß1. We investigated the role of integrin α5-specific signals in Marfan mice in which the cytoplasmic domain of integrin α5 was replaced with that of integrin α2 (denoted α5/2 chimera). METHODS: We crossed α5/2 chimeric mice with Fbn1mgR/mgR mice (mgR model of Marfan syndrome) to evaluate the survival rate and pathogenesis of TAAs among wild-type, α5/2, mgR, and α5/2 mgR mice. Further biochemical and microscopic analysis of porcine and mouse aortic SMCs investigated molecular mechanisms by which FN affects SMCs and subsequent development of TAAs. RESULTS: FN was elevated in the thoracic aortas from Marfan patients, in nonsyndromic aneurysms, and in mgR mice. The α5/2 mutation greatly prolonged survival of Marfan mice, with improved elastic fiber integrity, mechanical properties, SMC density, and SMC contractile gene expression. Furthermore, plating of wild-type SMCs on FN decreased contractile gene expression and activated inflammatory pathways whereas α5/2 SMCs were resistant. These effects correlated with increased NF-kB activation in cultured SMCs and mgR aortas, which was alleviated by the α5/2 mutation or NF-kB inhibition. CONCLUSIONS: FN-integrin α5 signaling is a significant driver of TAA in the mgR mouse model. This pathway thus warrants further investigation as a therapeutic target.

Boldine modulates glial transcription and functional recovery in a murine model of contusion spinal cord injury.

Membrane channels such as connexins (Cx), pannexins (Panx) and P2X 7 receptors (P2X 7 R) are permeable to calcium ions and other small molecules such as ATP and glutamate. Release of ATP and glutamate through these channels is a key mechanism driving tissue response to traumas such as spinal cord injury (SCI). Boldine, an alkaloid isolated from the Chilean boldo tree, blocks both Cx hemichannels (HC) and Panx. To test if boldine could improve function after SCI, boldine or vehicle was administered to treat mice with a moderate severity contusion-induced SCI. Boldine led to greater spared white matter and increased locomotor function as determined by the Basso Mouse Scale and horizontal ladder rung walk tests. Boldine treatment reduced immunostaining for markers of activated microglia (Iba1) and astrocytic (GFAP) markers while increasing that for axon growth and neuroplasticity (GAP-43). Cell culture studies demonstrated that boldine blocked glial HC, specifically Cx26 and Cx30, in cultured astrocytes and blocked calcium entry through activated P2X 7 R. RT-qPCR studies showed that boldine treatment reduced expression of the chemokine Ccl2, cytokine IL-6 and microglial gene CD68, while increasing expression of the neurotransmission genes Snap25 and Grin2b, and Gap-43. Bulk RNA sequencing (of the spinal cord revealed that boldine modulated a large number of genes involved in neurotransmission in in spinal cord tissue just below the lesion epicenter at 14 days after SCI. Numbers of genes regulated by boldine was much lower at 28 days after injury. These results indicate that boldine treatment ameliorates injury and spares tissue to increase locomotor function.

A Community-Based, Participatory, Multi-Component Intervention Increased Sales of Healthy Foods in Local Supermarkets-The Health and Local Community Project (SoL).

Project SoL was a 19-month (September 2012 to April 2014) community-based multi-component intervention based on the supersetting approach that was designed to promote healthier eating and physical activity among children and their families. The aim of this study was to examine the effects of a multi-component intervention (level 1) and a mass media intervention alone (level 2) compared to a control area (level 3) on food sales. The design was quasi-experimental. Weekly sales data for all Coop supermarkets in the intervention and control areas were analysed via longitudinal linear mixed-effects analyses. Significant increases in the sales of fish (total) (29%; p = 0.003), canned fish (31%; p = 0.025) and oatmeal (31%; p = 0.003) were found for the level 1 intervention area compared to the control area. In the level 2 intervention area, significant increases in the sales of vegetables (total) (17%; p = 0.038), fresh vegetables (20%; p = 0.01), dried fruit (51%; p = 0.022), oatmeal (19%; p = 0.008) and wholegrain pasta (58%; p = 0.0007) were found compared to the control area. The sales of canned fish increased by 30% in the level 1 area compared to the level 2 area (p = 0.025). This study demonstrated significant increases in the sales of healthy foods, both in the areas with multi-component and mass media interventions alone compared to the control area.

Indoor radon survey in Greenland and dose assessment.

Indoor radon and its decay products are the primary sources of the population's exposure to background ionizing radiation. Radon decay products are one of the leading causes of lung cancer, with a higher lung cancer risk for smokers due to the synergistic effects of radon decay products and cigarette smoking. A total of 459 year-long radon measurements in 257 detached and semi-detached residential homes in southwest and south Greenland were carried out, and a dose assessment for adults was performed. The annual arithmetic and geometric means of indoor radon concentrations was 10.5 ± 0.2 Bq m-3 and 8.0 ± 2.3 Bq m-3 in Nuuk, 139.0 ± 1.0 Bq m-3 and 97.3 ± 2.1 Bq m-3 in Narsaq, and 42.1 ± 0.7 Bq m-3 and 22.0 ± 3.1 Bq m-3 in Qaqortoq. Arithmetic and geometric mean radon concentration of 79.0 Bq m-3 and 50.3 Bq m-3 were estimated for adult, person-weighted living in south Greenland. The total number of detached and semi-detached residential homes where indoor radon is exceeding 100 Bq m-3, 200 Bq m-3, and 300 Bq m-3 is 37 homes (15.0%), 13 homes (5.2%), and 8 homes (3.2%), respectively. A positive correlation between indoor air radon concentrations and underlying geology was observed. The indoor radon contribution to the annual inhalation effective dose to an average adult was 0.5 mSv in Nuuk, 6.5 mSv in Narsaq, 2.0 mSv in Qaqortoq, and 4.0 mSv for south Greenland adult person weighted. The estimated annual average effective dose to adults in Narsaq is higher than the world's average annual effective dose of 1.3 mSv due to inhalation of indoor radon. Cost-efficient mitigation methods exist to reduce radon in existing buildings, and to prevent radon entry into new buildings.

Settings, populations, and time: a conceptual framework for public health interventions.

This paper presents a conceptual framework displaying how combinations of settings and populations seen in a long-term perspective may guide public health and health promotion planning and research. The notion of settings constitutes a key element of health promotion as stipulated by the Ottawa Charter from 1986. The setting approach highlights the individual, social and structural dimensions of health promotion. Likewise, the notion of populations and how they are selected forms a center pillar of public health. By joining the two perspectives, four combinations of intervention strategies appear by addressing: (1) a single population segment within a single setting, (2) multiple population segments within a single setting, (3) a single population segment within multiple settings or (4) multiple population segments within multiple settings. Furthermore, the addition of a time dimension inspired by the life-course perspective illustrates how trajectories of individuals and projects change settings and population segments as time goes by. The conceptual framework displays how systematic awareness of long-term, multi-setting, multi-population trajectories allow health promotion planners and researchers to systematically develop, plan and analyze their projects.