Evidence-informed health intervention planning that incorporates theoretical and empirical evidence and engages key stakeholders and community members or patients in the planning process results in interventions that are more effective. Nevertheless, exactly how and when to use evidence, theory, and community-based participation during planning represents a challenge. In this Perspective, we describe Intervention Mapping (IM), a framework for theory- and evidence-based health promotion program planning that addresses this challenge by providing a systematic and stepwise approach to planning interventions. IM has been used to develop health promotion interventions and implementation strategies in community and clinical settings globally, with over 1000 published articles employing the framework. In this Perspective, we also highlight recent and innovative applications of IM described in the articles of the Frontiers in Public Health Special Topic on IM. We conclude by discussing new directions in the application of IM including novel methods for identifying determinants of behavior and environmental conditions, the application of IM for planning implementation strategies, and IM for adaptation of evidence-based programs in new settings.

Abstract-Bone marrow mononuclear cells (BMCs) from 20 patients with extensive reperfused myocardial infarction (MI) were used to assess their myocardial regenerative capability "in vitro" and their effect on postinfarction left ventricular (LV) remodeling. Human BMCs were labeled, seeded on top of cryoinjured mice heart slices, and cultured. BMCs showed tropism for and ability to graft into the damaged mouse cardiac tissue and, after 1 week, acquired a cardiomyocyte phenotype and expressed cardiac proteins, including connexin43. In the clinical trial, autologous BMCs (78Ϯ41ϫ10 6 per patient) were intracoronarily transplanted 13.5Ϯ5.5 days after MI. There were no adverse effects on microvascular function or myocardial injury. No major cardiac events occurred up to 11Ϯ5 months. At 6 months, magnetic resonance showed a decrease in the end-systolic volume, improvement of regional and global LV function, and increased thickness of the infarcted wall, whereas coronary restenosis was only 15%. No changes were found in a nonrandomized contemporary control group. Thus, BMCs are capable of nesting into the damaged myocardium and acquire a cardiac cell phenotype in vitro as well as safely benefiting ventricular remodeling in vivo. Large-scale randomized trials are needed now to assess the clinical efficacy of this treatment.

Neuronal remodeling is a fundamental process by which the brain responds to environmental influences, e.g., during stress. In the hippocampus, chronic stress causes retraction of dendrites in CA3 pyramidal neurons. We have recently identified the glycoprotein M6a as a stress-responsive gene in the hippocampal formation. This gene is down-regulated in the hippocampus of both socially and physically stressed animals, and this effect can be reversed by antidepressant treatment. In the present work, we analyzed the biological function of the M6a protein. Immunohistochemistry showed that the M6a protein is abundant in all hippocampal subregions, and subcellular analysis in primary hippocampal neurons revealed its presence in membrane protrusions (filopodia͞ spines). Transfection experiments revealed that M6a overexpression induces neurite formation and increases filopodia density in hippocampal neurons. M6a knockdown with small interference RNA methodology showed that M6a low-expressing neurons display decreased filopodia number and a lower density of synaptophysin clusters. Taken together, our findings indicate that M6a plays an important role in neurite͞filopodium outgrowth and synapse formation. Therefore, reduced M6a expression might be responsible for the morphological alterations found in the hippocampus of chronically stressed animals. Potential mechanisms that might explain the biological effects of M6a are discussed. chronic stress ͉ hippocampus T he adult nervous system can be strongly influenced by sensory input from the outside environment. For example, prolonged exposure to adverse situations can have severe consequences for the brain, conferring susceptibility to certain psychiatric disorders. Indeed, chronic stress is one of the main factors known to trigger depression in humans (1). One of the most extensively studied regions in the brain is the hippocampal formation, which possesses a remarkable degree of plasticity and is particularly sensitive to stress. Studies in rodents and tree shrews demonstrated that chronic stress can cause alterations in neuronal processes. Stressed animals show morphological changes in CA3 pyramidal neurons, characterized by a reduction of apical dendritic branching and total dendritic length (2, 3). In addition, stressed rats also display a marked retraction of thorny excrescences and reduced synaptic density (4-6). Interestingly, antidepressant treatment can block these stress effects (7). Although there has been important progress regarding the understanding of the stress response and antidepressant action, the molecular pathways underlying these plastic alterations still remain largely unknown.By using subtractive hybridization libraries, we have recently identified the gene encoding the glycoprotein M6a as a stressresponsive gene. Expression levels for M6a are decreased in hippocampal tissue of tree shrews subjected to chronic psychosocial stress, and this down-regulation is prevented by chronic administration of the antidepressant clomipramine (8). Moreover, mice exp...