Promoter Context Research Articles

FOXO1 cysteine-612 mediates stimulatory effects of the coregulators CBP and PGC1α on FOXO1 basal transcriptional activity.

Hepatic production and release of metabolites, nutrients and micronutrient transporters is tightly regulated at the level of gene expression. In this regard, transcription factor FOXO1 modulates the expression of genes such as G6PC and SELENOP, encoding the catalytic subunit of glucose 6-phosphatase and the plasma selenium transporter selenoprotein P, respectively. Here, we analyzed the role of cysteine residues in FOXO1 in controlling its activity with respect to regulation of G6PC and SELENOP in HepG2 human hepatoma cells. None of the seven FOXO1 cysteines affected FOXO1 binding to DNA or its basal subcellular distribution. Whereas overexpression of wildtype FOXO1 caused a strong induction of both G6PC and SELENOP promoter activities and mRNA levels, the induction was lowered by approx. 50% if cysteine-deficient FOXO1 was overexpressed instead. Only the most C-terminal of the seven FOXO1 cysteines, Cys612, was required and sufficient to ensure full FOXO1 transactivation activity. Coexpression of FOXO1 coregulators, CBP or PGC1α, had a strong synergistic effect in stimulating G6PC promoter activity and expression, fully relying on the presence of FOXO1 Cys612. Similarly, a synergistic effect of FOXO1 and CBP was observed for SELENOP. In contrast, stimulation of SELENOP by PGC1α was independent of FOXO1-Cys612, due to the close proximity of a hepatocyte nuclear factor-4α binding site to the FOXO1 binding site within the SELENOP promoter, as demonstrated using mutant SELENOP promoter constructs. In summary, full basal FOXO1 transactivation activity relies on Cys612, which mediates synergistic effects of coregulators, CBP or PGC1α, on FOXO1 transcriptional activity. The extent of Cys612 contribution depends on the promoter context of FOXO1 target genes.

DeSUMOylation switches Kaiso from activator to repressor upon hyperosmotic stress.

Kaiso is a member of the BTB/POZ zinc finger family, which is involved in cancer progression, cell cycle control, apoptosis, and WNT signaling. Depending on promoter context, it may function as either a transcriptional repressor or activator. Previous studies found that Kaiso might be SUMOylated due to heat shock, but the biological significance of Kaiso SUMOylation is unclear. Here, we find that K42 is the only amino acid within Kaiso that is modified with SUMO. Kaiso is monoSUMOylated at lysine 42 in cell lines of kidney origin under normal physiological conditions. SUMOylated Kaiso can activate transcription from exogenous methylated promoters, wherein the deSUMOylated form of the protein kept the ability to be a repressor. Rapid Kaiso deSUMOylation occurs in response to hyperosmotic stress and is reversible upon return to an isotonic environment. DeSUMOylation occurs within minutes in HEK293 cells treated with 100 mM NaCl and relaxes in 3 h even in a salt-containing medium. Genomic editing of Kaiso by conversion of K42 into R42 (K42R) in HEK293 cells that resulted in fully deSUMOylated endogenous protein led to misregulation of genes associated with ion transport, blood pressure, and the immune response. TRIM25 was significantly repressed in two K42R HEK293 clones. By a series of rescue experiments with K42R and KO HEK293 cells, we show that TRIM25 is a direct transcriptional target for Kaiso. In the absence of Kaiso, the level of TRIM25 is insensitive to hyperosmotic stress. Extending our observations to animal models, we show that in response to a high salt diet, Kaiso knockout mice are characterized by significantly higher blood pressure increases when compared to wild-type animals. Thus, we propose a novel biological role for Kaiso in the regulation of homeostasis.

Research capacity for local innovation: the case of conservation agriculture in Ethiopia, Malawi and Mozambique

ABSTRACTPurpose: The limited uptake of improved agricultural practices in Africa raise questions on the functionality of current agricultural research systems. Our purpose is to explore the capacity for local innovation within the research systems of Ethiopia, Malawi and Mozambique.Design/methodology/approach: Using Conservation Agriculture (CA) as a case study, we qualitatively explore with 26 locally based agricultural researchers the context of CA research and promotion, including their perceptions on persistent research gaps and issues in closing them.Findings: Respondents identified that CA was not yet a finished product, with concerns regarding the benefit, feasibility and relevance of CA implementation. They asserted that while further adaptation was required, they were unable to do this due to institutional constraints within their research, extension and policy contexts.Practical implications: We find that CA continues to be considered a donor-driven intervention in its current form and requires substantial further adaptation to local contexts before researchers will deem it ready for farmer uptake. The five research gaps identified by respondents highlight practical areas where further adaptations must occur.Theoretical implications: Our findings suggest a lack of participatory research and extension most likely reflects limited financial, human and social capital to implement more participatory approaches. Without addressing these capacities, widespread adoption of complex farming systems change appears unlikely.Originality/Value: Whilst many studies have identified a need for local innovation to enable CA utilisation, few have qualitatively explored directly with local researchers the capacity of such systems to do so. We address this gap in the literature.

The Yin and Yang of YY1 in tumor growth and suppression.

Yin Yang-1 (YY1) is a zinc finger protein and member of the GLI-Kruppel family that can activate or inactivate gene expression depending on interacting partners, promoter context and chromatin structure, and may be involved in the transcriptional control of ∼10% of the total mammalian gene set. A growing body of literature indicates that YY1 is overexpressed in multiple cancer types and that increased YY1 levels correlate with poor clinical outcomes in many cancers. However, the role of YY1 in the promotion or suppression of tumor growth remains controversial and its regulatory effects may be tumor cell type dependent at least in experimental systems. The molecular mechanisms responsible for the apparently conflicting roles of YY1 are not yet fully elucidated. This review highlights recent advances in our understanding of regulatory insights involving YY1 function in a range of cancer types. For example, YY1's roles in tumor growth involve stabilization of hypoxia-inducible factor HIF-1α in a p53 independent manner, negative regulation of miR-9 transcription, control of MYCT1 transcription, a novel miR-193a-5p-YY1-APC axis, intracellular ROS and mitochondrial superoxide generation, p53 reduction and EGFR activation, control of genes associated with mitochondrial energy metabolism and miRNA regulatory networks involving miR-7, miR-9, miR-34a, miR-186, miR-381, miR-584-3p and miR-635. On the other hand, tumor suppressor roles of YY1 appear to involve YY1 stimulation of tumor suppressor BRCA1, increased Bax transcription and apoptosis involving cytochrome c release and caspase-3/-7 cleavage, induction of heme oxygenase-1, inhibition of pRb phosphorylation and p21 binding to cyclin D1 and cdk4, reduced expression of long noncoding RNA of SOX2 overlapping transcript, and MUC4/ErbB2/p38/MEF2C-dependent downregulation of MMP-10. YY1 expression is associated with that of cancer stem cell markers SOX2, BMI1 and OCT4 across many cancers suggesting multidynamic regulatory control and groups of cancers with distinct molecular signatures. Greater understanding of the mechanistic roles of YY1 will in turn lead to the development of more specific approaches to modulate YY1 expression and activity with therapeutic potential.

Functional Characterization of Insulation Effect for Synthetic Gene Circuits in Mammalian Cells.

Insulators are noncoding gene regulatory elements in eukaryotic genome, which function as chromatin partitioning boundaries, and block interference across different chromatin domains. To facilitate modular construction of synthetic gene circuit that is usually composed of multiple transcription cassettes, unwanted cross-regulations between different cassettes should be avoided. Here, we developed a quantitative method to characterize the functional effect of three insulators on the cross-regulations of six promoters in mammalian cells. We showed that the unwanted cross-regulations displayed a threshold-like effect, and the threshold position varied along with the context of promoters and insulators. We tested the function of insulators in both cascade and sensory switch circuits assembled in episomal plasmid vectors, and showed that the insulation effect was mainly revealed on the first regulatory layer of the cascade circuit. A deviation on the response curve of the sensory switch circuit with or without insulators was observed, but response intensity of some sensory switch circuits were not affected. Therefore, our results provided a general guide on the selection of insulators with varying promoters in episomal synthetic gene circuits in mammalian cells, which may be useful to reduce the effect of the unwanted cross-regulations.

Air Pollution and Grassroots Echoes of “Ecological Civilization” in Rural China

AbstractThis article places the study of rural environmental activism in the wider context of the Chinese government's promotion of Ecological Civilization (shengtai wenming 生态文明). Ecological Civilization is, we argue, a top-down imaginary of China's future that opens up space for environmental agency while setting authoritative standards for how to frame protests in a logic of science and social stability. The article compares how residents in a small cluster of villages in Zhejiang province dealt with different sources of air pollution over a span of ten years: how, when and why they chose to negotiate with local officials and industrial managers to prevent or reduce air pollution, and what the outcome was. We found that in addition to a consciousness of the right to protest, villagers had come to regard the ability to evoke science in negotiations with officials and industrial managers as crucial for success. We suggest that the forms of environmental activism we observed were in effect “containable protests” that befit the state-initiated national imaginary of an ecologically civilized world.

Patient-provider relationship and perceived provider weight bias among American Indians and Alaska Natives.

SummaryObjectiveThe objective of this study was to examine patient–provider relationships among American Indians and Alaska Native (AI/AN) patients by examining associations between patient activation, perceived provider weight bias and working alliance. Patient activation is generally defined as having the knowledge, skills and confidence to manage one's health.MethodsAmong a sample of 87 AI/AN adults presenting for general medical care at an urban clinic in the north‐west region of the USA, ordinary least squares regression analysis was completed to examine associations.ResultsBetter working alliance scores were associated with increased patient activation, while perceived provider weight bias was associated with reduced patient activation. In addition, those with class II obesity had decreased patient activation.ConclusionThese findings point to the importance of a positive patient–provider relationship in AI/ANs. Optimal patient engagement and subsequent health outcomes warrant additional consideration of patients' perceptions of provider weight bias within the context of health promotion and interventions.

Adolescent health promotion and the School Health Program: complexity in the articulation of health and education.

Objective To analyze the context of health promotion with adolescents in the health and education interface focusing on the actions of the Brazilian School Health Program. Qualitative study conducted in 2015 with professionals working in the Regional Executive Coordination IV, in Fortaleza, Ceará. The data obtained in the interview were processed in the ALCESTE program. 17 health professionals and 22 education professionals participated in the study. The organization of spontaneous demand causes disharmony in the scheduled visits and health actions in the school. The difficulties in the implementation of the School Health Program were demonstrated by the lack of knowledge, the lack of planning among the sectors and the different demarcations in the territory. The professionals' lack of knowledge regarding the program and the lack of action planning confirm the disarticulation of the education and health sectors, although they indicate the possibilities of this inter-sectoral practice.

The cultural contexts of gender stereotypes and health promotion: the use of narrative and culture-centred approaches

The cultural contexts of gender stereotypes and health promotion: the use of narrative and culture-centred approaches

Health by Design: Interweaving Health Promotion into Environments and Settings.

The important influence of the environmental context on health and health behavior—which includes place, settings, and the multiple environments within place and settings—has directed health promotion planners from a focus solely on changing individuals, toward a focus on harnessing and changing context for individual and community health promotion. Health promotion planning frameworks such as Intervention Mapping provide helpful guidance in addressing various facets of the environmental context in health intervention design, including the environmental factors that influence a given health condition or behavior, environmental agents that can influence a population’s health, and environmental change methods. In further exploring how to harness the environmental context for health promotion, we examine in this paper the concept of interweaving of health promotion into context, defined as weaving or blending together health promotion strategies, practices, programs, and policies to fit within, complement, and build from existing settings and environments. Health promotion interweaving stems from current perspectives in health intervention planning, improvement science and complex systems thinking by guiding practitioners from a conceptualization of context as a backdrop to intervention, to one that recognizes context as integral to the intervention design and to the potential to directly influence health outcomes. In exploring the general approach of health promotion interweaving, we examine selected theoretical and practice-based interweaving concepts in relation to four key environments (the policy environment, the information environment, the social/cultural/organizational environment, and the physical environment), followed by evidence-based and practice-based examples of health promotion interweaving from the literature. Interweaving of health promotion into context is a common practice for health planners in designing health promotion interventions, yet one which merits further intentionality as a specific health promotion planning design approach.

Key Design Considerations Using a Cohort Stepped-Wedge Cluster Randomised Trial in Evaluating Community-Based Interventions: Lessons Learnt from an Australian Domiciliary Aged Care Intervention Evaluation

The ‘stepped-wedge cluster randomised trial’ (SW-CRT) harbours promise when for ethical or practical reasons the recruitment of a control group is not possible or when a staggered implementation of an intervention is required. Yet SW-CRT designs can create considerable challenges in terms of methodological integration, implementation, and analysis. While cross-sectional methods in participants recruitment of the SW-CRT have been discussed in the literature the cohort method is a novel feature that has not been considered yet. This paper provides a succinct overview of the methodological, analytical, and practical aspects of cohort SW-CRTs. We discuss five issues that are of special relevance to SW-CRTs. First, issues relating to the design, secondly size of clusters and sample size; thirdly, dealing with missing data in the fourth place analysis; and finally, the advantages and disadvantages of SW-CRTs are considered. An Australian study employing a cohort SW-CRT to evaluate a domiciliary aged care intervention is used as case study. The paper concludes that the main advantage of the cohort SW-CRT is that the intervention rolls out to all participants. There are concerns about missing a whole cluster, and difficulty of completing clusters in a given time frame due to involvement frail older people. Cohort SW-CRT designs can be successfully used within public health and health promotion context. However, careful planning is required to accommodate methodological, analytical, and practical challenges.

Evaluating the European Health Literacy Survey Questionnaire in Patients with Stroke: A Latent Trait Analysis Using Rasch Modeling.

The effective self-management and treatment of long-term disability after stroke depends greatly on the health literacy of patients. The European Health Literacy Survey Questionnaire (HLS-EU-Q) is a comprehensive and theory-based measure that captures multiple self-perceived competencies of health literacy and covers a diverse range of health contexts. However, there is no psychometric evidence on the HLS-EU-Q in the stroke population. The aim of this study was to examine the validity of the HLS-EU-Q in patients with stroke using Rasch analysis. We compared the model deviance among the one-domain, three-domain, four-domain, and 12-domain structures using likelihood ratio tests to determine the dimensionality of the HLS-EU-Q. Thereafter, we examined the unidimensionality of each domain, local independence, item fit, response categories, and differential item functioning (DIF) for the best fitting structure. A total of 311 patients with stroke participated in this study. Rasch analysis revealed that the 12-domain HLS-EU-Q demonstrated the best data-model fit. The original 4-point scales showed disordering, which can be corrected by rescaling them as 3-point scales with the two middle categories collapsed. All 47 items in the rescaled HLS-EU-Q fit the 12-domain Rasch model, demonstrated local independence, assessed the 12 unidimensional domains respectively, and had invariant difficulties between different age or education groups of the patients with stroke. We recommend using the 12-domain scores of the rescaled HLS-EU-Q to comprehensively and accurately capture the competencies to access, understand, appraise, and apply health information within the three health contexts of healthcare, disease prevention, and health promotion for patients with stroke.

Improve Adult Health Life in Western Sydeny Through Health Promotion Models

This report will focus on a new health development initiative for the Western Sydney Adolescents and their health needs in terms of promoting physical activity and exercise because it helps them live longer and better lives and become more energetic. The target group are fairly sedentary individuals and consume copious amounts of energy dense foods, which are contributing to the burgeoning obesity risk factors in the community. A sedentary lifestyle contributes towards a range of cardiovascular diseases and health problems including heart disease, obesity, high blood pressure, high cholesterol and many types of cancers (Meyer, 2007). Successfully tackling obesity in a health promotion context, is a long-term, large-scale commitment that will require both individual responsibility and action together with a population-based approach, driven by partnerships between governments, businesses, and communities. The current prevalence of obesity in the population has been at least 30 years in the making, and will take considerable time to reverse the trends and its impacts and determinants on health (Roth, 2011). This article will outline the costing requirements and the evaluation methods that will be used in our adolescent obesity health promotion and prevention management strategy. This will be achieved by using a combination of educational and awareness campaigns, public advertising, healthy urban planning, imposing a ban on canteen junk food and establishing a health and wellbeing telephone hotline and social networking group. This will be evaluated for feasibility using cost-benefit analysis to determine whether each strategy or approach is to be implemented or not.

LIM-Only Protein FHL2 Is a Negative Regulator of Transforming Growth Factor β1 Expression.

Transforming growth factor β1 (TGF-β1) is a master cytokine in many biological processes, including tissue homeostasis, epithelial-to-mesenchymal transition, and wound repair. Here, we report that four and a half LIM-only protein 2 (FHL2) is a critical regulator of TGF-β1 expression. Devoid of a DNA-binding domain, FHL2 is a transcriptional cofactor that plays the role of coactivator or corepressor, depending on the cell and promoter contexts. We detected association of FHL2 with the TGF-β1 promoter, which showed higher activity in Fhl2-/- cells than in wild-type (WT) cells in a reporter assay. Overexpression of FHL2 abrogates the activation of the TGF-β1 promoter, whereas the upregulation of TGF-β1 gene transcription correlates with reduced occupancy of FHL2 on the promoter. Moreover, ablation of FHL2 facilitates recruitment of RNA polymerase II on the TGF-β1 promoter, suggesting that FHL2 may be involved in chromatin remodeling in the control of TGF-β1 gene transcription. Enhanced expression of TGF-β1 mRNA and cytokine was evidenced in the livers of Fhl2-/- mice. We tested the in vivo impact of Fhl2 loss on hepatic fibrogenesis that involves TGF-β1 activation. Fhl2-/- mice developed more severe fibrosis than their WT counterparts. These results demonstrate the repressive function of FHL2 on TGF-β1 expression and contribute to the understanding of the TGF-β-mediated fibrogenic response.

Saúde vocal e mhealth: novas alternativas para antigos cenários

The world is experiencing the communication age, and health is among the areas that reap benefits from the insertion of new resources into people’s lives. In this context, Information and Communication Technologies (ICTs) hold a prominent place, being applied to information processing, storage, search and transmission in digital format, providing increased agility and reliability to information exchange(1,2). In the health area, ICTs play a progressively more important role, being present in the areas of clinical, managerial and assistance practices, as well as in support to decision-making on the part of professionals and managers.In this scenario, technology can influence and modify people’s way of living and acting, even when these issues are related to the health promotion and care context. The relevance of incorporating technologies into health care is thus reassured(3,4). With regard to vocal health, it implies a re-dimensioning of self-care, once the disorders of the vocal apparatus are part of the universe of professionals who use their voice, with emphasis on the teachers, this being a reality that requires confrontation through political and technological measures that offer resolution for such a recurrent problem as this.A study(5) carried out with 351 female teachers working at municipal elementary schools of Fortaleza, Ceara, Brazil, has shown that more than half of them presented more than six vocal symptoms and that, despite perceiving themselves exposed to more than six vocal risk factors, they had never participated in a vocal health program, which corroborates other Brazilian studies(6,7).It should be emphasized that, in addition to the shortage of educational actions in vocal health, Brazilian public policies and legislation aimed at teachers’ health are flawed and restricted(8). Therefore, attention is drawn to the importance of developing communication campaigns addressing health and the technological resources aimed at vocal health, in order to reinforce the need for continuously taking care of the voice.Given this data, it is believed that the expansion of voice knowledge and the use of novel communication strategies may favor the development of an advantageous work that contributes to the learning process and to the well-being of each voice-centered professional. With this aim, several technologies can be employed, among which mobile health technologies (mHealth) stand out.The area of mobile health research (mHealth), a branch of electronic health (eHealth) defined as “the use of computing and mobile communication technologies in health care and public health”, has been steadily expanding. Mobile health applications serve a heterogeneous public - doctors, nurses, patients, caregivers and healthy people(9) - and suit a range of purposes(10), such as information in a number of health areas, adherence to treatment(s) and disease management.In Brazil, there are a few studies addressing the topic of vocal health and technology. Nevertheless, it is possible to observe the insertion of several tools in the daily life of speech therapists, which support them and are recognized as types of technology. Booklets, softwares, informative applications and distance education platforms, all aimed at vocal health, can be cited as examples of facilitation strategies in speech therapy practices, which do not offer interactivity, though.Based on the aforementioned resources, it is believed that mHealth technology, given its dynamism and the facilitations it offers, such as the possibility to carry out actions at any time and anywhere, can contribute to the promotion of teachers’ vocal health, since their multiple assignments and lack of time often lead the teacher to overlook their problems, only seeking help after the onset of vocal change(s)(11).In view of the shortage of applications favoring vocal health care, and by means of a partnership between the Graduate Program in Public Health of the University of Fortaleza and the Laboratory of Innovation and New Businesses of the Information Technology Application Nucleus (Nucleo de Aplicacao em Tecnologia da Informacao - NATI) it was developed, at this institution, the VoiceGuard application, a tool that provides individualized support for the management of voice usage. This application presents as distinguishing features the offer of a variety of resources for extensive and comprehensive management and monitoring of vocal health, even on a real-time basis, thus favoring the teachers’ autonomy and the reduction of vocal disorders. This technology is recognized as an important tool for vocal health promotion and care, constituting a modern resource for dealing with an old problem: the vocal disorders affecting teachers.The Brazilian Journal on Health Promotion believes in the dissemination of this and other innovative technological products applied to health and well-being, given the speed of scientific interactions, in favor of the unlimited access to health.

Dissection of TALE-dependent gene activation reveals that they induce transcription cooperatively and in both orientations.

Plant-pathogenic Xanthomonas bacteria inject transcription activator-like effector proteins (TALEs) into host cells to specifically induce transcription of plant genes and enhance susceptibility. Although the DNA-binding mode is well-understood it is still ambiguous how TALEs initiate transcription and whether additional promoter elements are needed to support this. To systematically dissect prerequisites for transcriptional initiation the activity of one TALE was compared on different synthetic Bs4 promoter fragments. In addition, a large collection of artificial TALEs spanning the OsSWEET14 promoter was compared. We show that the presence of a TALE alone is not sufficient to initiate transcription suggesting the requirement of additional supporting promoter elements. At the OsSWEET14 promoter TALEs can initiate transcription from various positions, in a synergistic manner of multiple TALEs binding in parallel to the promoter, and even by binding in reverse orientation. TALEs are known to shift the transcriptional start site, but our data show that this shift depends on the individual position of a TALE within a promoter context. Our results implicate that TALEs function like classical enhancer-binding proteins and initiate transcription in both orientations which has consequences for in planta target gene prediction and design of artificial activators.

DESIGN AND IMPLEMENTATION OF TABRIZ STROKE REGISTRY

Abstract Introduction: Stroke is a leading cause of mortality and disability worldwide; specifically, overwhelming in developing countries. Stroke registry is a beneficial infrastructure for clinical audits of stroke, as well as related surveillances, epidemiologic studies, evidence-based medicine and decision-making (both clinical and for health policies). However, few stroke registries have been designed and developed worldwide. Methods: The structure of the stroke registry was designed by a thorough literature review of the stroke registries worldwide, assessed by an expert panel customized to Iranian culture and regional conditions in Tabriz. The software used for this registry is currently offline and expected to be online after specific progress of the registry. It is confirmed by the national council of stroke registries, and future stroke registries could join it in a national network. Security of information and ethical issues were considered. Results: Since 2014, Tabriz stroke registry is being implemented prospectively. Since now information of about 4000 stroke cases have been collected. The collected data include information of demography, pre-hospital, EMS (emergency medical service), clinical findings, primary imaging, lab findings, history of risk factors, drug history, discharge, follow up, GCS, MRS, NIHSS, dysphagia, rehabilitation, complications, instructions, diagnoses, and treatments (medical, surgical, interventional) of stroke patients. The collected data are being entered to the software and the registry is currently going on. Conclusion: Tabriz stroke registry has provided the efficient context for clinical and research promotion of stroke care which would influence this care in northwest Iran and eventually, the whole country.

Analysis of Historical Context of Health Promotion and Structural Constraints

Analysis of Historical Context of Health Promotion and Structural Constraints

The IRCCS Policlinico San Matteo in Pavia as optimal arena for health promotion: the WHP experience

Workplaces have been recognized as favored context for health promotion as they directly affect workers’ physical, psychological and social well-being. The IRCCS Policlinico San Matteo Foundation, in Pavia, has great potential as a setting for health promotion due to its significant workforce, including approximately 3000 employees in 2015. This is therefore well-suited to address both occupational health issues and …

Involuntary Outpatient Commitment and the Elusive Pursuit of Violence Prevention.

Involuntary outpatient commitment (OPC)-also referred to as 'assisted outpatient treatment' or 'community treatment orders'-are civil court orders whereby persons with serious mental illness and repeated hospitalisations are ordered to adhere to community-based treatment. Increasingly, in the United States, OPC is promoted to policy makers as a means to prevent violence committed by persons with mental illness. This article reviews the background and context for promotion of OPC for violence prevention and the empirical evidence for the use of OPC for this goal. Relevant publications were identified for review in PubMed, Ovid Medline, PsycINFO, personal communications, and relevant Internet searches of advocacy and policy-related publications. Most research on OPC has focussed on outcomes such as community functioning and hospital recidivism and not on interpersonal violence. As a result, research on violence towards others has been limited but suggests that low-level acts of interpersonal violence such as minor, noninjurious altercations without weapon use and arrests can be reduced by OPC, but there is no evidence that OPC can reduce major acts of violence resulting in injury or weapon use. The impact of OPC on major violence, including mass shootings, is difficult to assess because of their low base rates. Effective implementation of OPC, when combined with intensive community services and applied for an adequate duration to take effect, can improve treatment adherence and related outcomes, but its promise as an effective means to reduce serious acts of violence is unknown.