Improving Retention in Mental Health and Psychosocial Support Interventions: An Analysis of Completion Rates across a Multi-Site Trial with Refugee, Migrant, and Host Communities in Latin America.

Research on mental health and psychosocial support (MHPSS) interventions within refugee and migrant communities has increasingly focused on evaluating implementation, including identifying strategies to promote retention in services. This study examines the relationship between participant characteristics, study setting, and reasons for intervention noncompletion using data from the Entre Nosotras feasibility trial, a community-based MHPSS intervention targeting refugee, migrant, and host community women in Ecuador and Panama that aimed to promote psychosocial wellbeing. Among 225 enrolled women, approximately half completed the intervention, with varying completion rates and reasons for nonattendance across study sites. Participants who were older, had migrated for family reasons, had spent more time in the study community, and were living in Panamá (vs. Ecuador) were more likely to complete the intervention. The findings suggest the need to adapt MHPSS interventions to consider the duration of access to the target population and explore different delivery modalities including the role of technology and cellular devices as reliable or unreliable source for engaging with participants. Engaging younger, newly arrived women is crucial, as they showed lower completion rates. Strategies such as consulting scheduling preferences, providing on-site childcare, and integrating MHPSS interventions with other programs could enhance intervention attendance.

Accessibility and Perceived Impact of a Group Psychosocial Intervention for Women in Ecuador: A Comparative Analysis by Migration Status.

There is increasing guidance promoting the provision of mental health and psychosocial support programs to both migrant and host community members in humanitarian settings. However, there is a lack of information on the respective experiences and benefits for migrant and host community members who are participating in mental health and psychosocial support programming. We evaluated a community-based psychosocial program for migrant and host community women, Entre Nosotras, which was implemented with an international non-governmental organization in Ecuador in 2021. Data on participant characteristics and psychosocial wellbeing were collected via pre/post surveys with 143 participants, and qualitative interviews were conducted with a subset (n = 61) of participants. All quantitative analyses were conducted in STATA, and qualitative analysis was done in NVivo. Attendance was higher for host community members. Specifically, 71.4% of host community members attended 4-5 sessions, whereas only 37.4% of migrants attended 4-5 sessions (p = 0.004). Qualitative analysis shows that the intervention was less accessible for migrants due to a variety of structural barriers. However, this analysis also demonstrated that both groups of women felt a greater sense of social connectedness after participating in the program and expressed gratitude for the bonds they formed with other women. Some migrant women described negative experiences with the host community because they felt as though they could not confide in host community women and speak freely in front of them. These results underscore how the migratory context influences the implementation of mental health and psychosocial support (MHPSS) programs. As humanitarian guidelines continue to emphasize the integration of host community members and displaced persons, it is critical to account for how the same intervention may impact these populations differently.

Strategies to improve the implementation and effectiveness of community-based psychosocial support interventions for displaced, migrant and host community women in Latin America.

As evidence supporting the effectiveness of mental health and psychosocial interventions grows, more research is needed to understand optimal strategies for improving their implementation in diverse contexts. We conducted a qualitative process evaluation of a multicomponent psychosocial intervention intended to promote well-being among refugee, migrant and host community women in three diverse contexts in Ecuador and Panamá. The objective of this study is to describe the relationships among implementation determinants, strategies and outcomes of this community-based psychosocial intervention. The five implementation strategies used in this study included stakeholder engagement, promoting intervention adaptability, group and community-based delivery format, task sharing and providing incentives. We identified 10 adaptations to the intervention and its implementation, most of which were made during pre-implementation. Participants (n = 77) and facilitators (n = 30) who completed qualitative interviews reported that these strategies largely improved the implementation of the intervention across key outcomes and aligned with the study's intervention and implementation theory of change models. Participants and facilitators also proposed additional strategies for improving reach, implementation and maintenance of this community-based psychosocial intervention.

Mixed-methods evaluation of a group psychosocial intervention for refugee, migrant and host community women in Ecuador and Panamá: Results from the Entre Nosotras cluster randomized feasibility trial.

Community-based psychosocial interventions are key elements of mental health and psychosocial support; yet evidence regarding their effectiveness and implementation in humanitarian settings is limited. This study aimed to assess the appropriateness, acceptability, feasibility and safety of conducting a cluster randomized trial evaluating two versions of a group psychosocial intervention. Nine community clusters in Ecuador and Panamá were randomized to receive the standard version of the Entre Nosotras intervention, a community-based group psychosocial intervention co-designed with community members, or an enhanced version of Entre Nosotras that integrated a stress management component. In a sample of 225 refugees, migrants and host community women, we found that both versions were safe, acceptable and appropriate. Training lay facilitators to deliver the intervention was feasible. Challenges included slow recruitment related to delays caused by the COVID-19 pandemic, high attrition due to population mobility and other competing priorities, and mixed psychometric performance of psychosocial outcome measures. Although the intervention appeared promising, a definitive cluster randomized comparative effectiveness trial requires further adaptations to the research protocol. Within this pilot study we identified strategies to overcome these challenges that may inform adaptations. This comparative effectiveness design may be a model for identifying effective components of psychosocial interventions.

Evaluating the feasibility of a group psychosocial intervention for migrant and host community women in Ecuador and Panamá: protocol for a multi-site feasibility cluster trial.

BACKGROUND: Community- and strengths-based psychosocial interventions are central to mental health and psychosocial support guidelines, but rigorous evidence regarding the effectiveness of these interventions is limited. The complexity and variability that is inherent to many community-based psychosocial interventions requires innovative strategies in order to facilitate the comparability and synthesis across research studies without compromising the fit and appropriateness of interventions to specific study populations and context. Entre Nosotras is a community-based psychosocial intervention developed for migrant and host community women that is designed to be flexible enough to enable integration of external intervention components and adaptable to diverse study contexts and populations. This protocol describes a study that aims to evaluate the appropriateness, acceptability, and feasibility of integrating a standardized stress management intervention into Entre Nosotras. METHODS: This study will evaluate the appropriateness, acceptability, feasibility, and safety of intervention and research procedures for a cluster randomized comparative effectiveness trial conducted in Ecuador and Panamá with migrant and host community women. In this feasibility trial, we will allocate communities nested within the three study sites to the integrated Entre Nosotras + stress management intervention versus Entre Nosotras alone through stratified randomization. Migrant and host community women residing in these study communities who report low to moderate levels of distress will be allocated to the intervention condition that their community is assigned (n = 220 total). We will collect quantitative measures of psychosocial wellbeing, psychological distress, coping, social support, and functioning from study participants. We will collect quantitative measures of fidelity and facilitator competencies through observation and facilitator self-assessment. Data on appropriateness, acceptability, feasibility, and safety will be gathered from participants and facilitators through quantitative assessments at 0, 5, and 10 weeks post-enrollment and qualitative interviews conducted with all facilitators and a subset of 70 study participants during the post-intervention follow-up period. DISCUSSION: Results from this feasibility trial will determine whether a multi-site cluster randomized comparative effectiveness trial of an adaptable community-based psychosocial intervention for migrant and host community women is relevant, acceptable, and feasible. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05130944 . Registered November 23, 2021-retrospectively registered.

Community-based participatory design of a psychosocial intervention for migrant women in Ecuador and Panama.

There is increasing evidence supporting the effectiveness of scalable mental health and psychosocial support (MHPSS) interventions delivered by non-specialists for improving wellbeing among migrant populations in humanitarian settings. Balancing fidelity in the implementation of evidence-based MHPSS interventions with their fit to the needs and preferences of new populations and contexts remains a challenge when introducing MHPSS interventions in new settings. This paper describes a community-based participatory approach to MHPSS intervention design incorporating processes to promote local adaptability and fit while maintaining standardized elements of existing MHPSS interventions. We conducted a mixed-methods study to design a community-based MHPSS intervention that fit the mental health and psychosocial needs of migrant women in three sites in Ecuador and Panama. Drawing from a set of community-based participatory research methods, we identified the priority mental health and psychosocial needs among migrant women, co-developed intervention mechanisms that aligned with those needs, matched mechanisms to existing psychosocial intervention components, and iteratively piloted and refined the intervention with community stakeholders. The resulting intervention was a five-session, lay facilitator-delivered group intervention titled, Entre Nosotras ('among/between us'). The intervention combined elements of individual and community problem solving, psychoeducation, stress management, and social support mobilization to address prioritized problems including psychological distress, safety, community connectedness, xenophobia and discrimination, and social support. This research outlines an emphasis on the social dimension of psychosocial support, as well as a process for balancing fit and fidelity in intervention design and implementation.

Obesity-Modified CD4+ T-Cells Promote an Epithelial-Mesenchymal Transition Phenotype in Prostate Cancer Cells.

Obesity is associated with low-grade chronic inflammation, and metabolic dysregulation. Evidence shows that chronic inflammation inhibits protective immunity mediated by CD4+ T cells. Additionally, obesity-induced inflammation affects prostate cancer progression. However, the effect of obesity on CD4+ T-cell- response to prostate cancer is not well understood. To investigate whether obesity induces changes in CD4+ T cell cytokine profile, cytokine expression was measured in splenic CD4+ T-cells from 10-week-old male C57Bl/6 mice exposed to conditioned media (CM) from macrophages grown in sera from obese subjects. Additionally, expression levels of key regulators of Epithelial-Mesenchymal Transition (EMT) were measure in prostate cancer epithelial cells exposed to conditioned media from obesity-modified T-cells. Cell migration and invasion was measured in prostate cancer epithelial cells exposed to CM from obesity-modified CD4+ T-cells. Obesity suppressed the expression of IFNγ and IL-2 in CD4+ T-cells but up-regulated the expression of IL-6. Prostate epithelial cancer cells exposed to conditioned media from obesity-modified T cell increased the expression of EMT markers and showed a higher invasive and migratory capacity.

Adipocyte-Specific Ablation of PU.1 Promotes Energy Expenditure and Ameliorates Metabolic Syndrome in Aging Mice.

Objective: Although PU.1/Spi1 is known as a master regulator for macrophage development and function, we have reported previously that it is also expressed in adipocytes and is transcriptionally induced in obesity. Here, we investigated the role of adipocyte PU.1 in the development of the age-associated metabolic syndrome. Methods: We generated mice with adipocyte-specific PU.1 knockout, assessed metabolic changes in young and older adult PU.1fl/fl (control) and AdipoqCre PU.1fl/fl (aPU.1KO) mice, including body weight, body composition, energy expenditure, and glucose homeostasis. We also performed transcriptional analyses using RNA-Sequencing of adipocytes from these mice. Results: aPU.1KO mice have elevated energy expenditure at a young age and decreased adiposity and increased insulin sensitivity in later life. Corroborating these observations, transcriptional network analysis indicated the existence of validated, adipocyte PU.1-modulated regulatory hubs that direct inflammatory and thermogenic gene expression programs. Conclusion: Our data provide evidence for a previously uncharacterized role of PU.1 in the development of age-associated obesity and insulin resistance.

Age-related increase in IL-17 activates pro-inflammatory signaling in prostate cells.

BACKGROUND: A close relationship between aging, inflammation, and prostate cancer is widely accepted. Aging is accompanied by a progressive increase in pro-inflammatory cytokines, including interleukin 17 (IL-17), a key pro-inflammatory cytokine that becomes dysregulated with age. However, the contribution of IL-17 to age-related prostate tumorigenesis remains unclear. The aim of this study was to investigate the role of age-related IL-17 dysregulation in prostate tumorigenesis. METHODS: Serum and splenic T-lymphocytes from young GPAT-1 knock-out aging-mimic T cell mice as well as young and aged wild-type mice were collected. shRNA was used to knock down the IL-17 receptor in LNCaP prostate cancer cells and RWPE-1 non-transformed prostate epithelial cells, which were then exposed to the mouse sera or conditioned media from stimulated T-lymphocytes. NF-κB activation, NF-κB target gene expression, and cell proliferation were all measured in these cells by luciferase assay, qPCR, Western blot analysis, and MTT assay, respectively. RESULTS: T-lymphocyte-secreted IL-17 from aging-mimic mice induced NF-κB activity and target gene expression in LNCaP and RWPE-1 cells. It also promoted proliferation of these cells. CONCLUSION: Aging-mimic T cell mice produce increased levels of IL-17, which stimulates the pro-inflammatory NF-κB pathway in prostate epithelial cells. NF-κB increases inflammation, carcinogenesis and metastatic potential in the prostate. These findings provide evidence that the dysregulation of cytokine production seen in aged T cells may directly contribute to the increased risk for prostate cancer in the elderly.

Mitochondrial glycerol-3-phosphate acyltransferase-1 is essential for murine CD4(+) T cell metabolic activation.

Glycerol-3-phosphate acyltransferase-1 is the first rate limiting step in de novo glycerophospholipid synthesis. We have previously demonstrated that GPAT-1 deletion can significantly alter T cell function resulting in a T cell phenotype similar to that seen in aging. Recent studies have suggested that changes in the metabolic profile of T cells are responsible for defining specific effector functions and T cell subsets. Therefore, we determined whether T cell dysfunction in GPAT-1 (-/-) CD4(+) T cells could be explained by changes in cellular metabolism. We show here for the first time that GPAT-1 (-/-) CD4(+) T cells exhibit several key metabolic defects. Striking decreases in both the oxygen consumption rate (OCR) and the extracellular acidification rate (ECAR) were observed in GPAT-1 (-/-) CD4(+) T cells following CD3/CD28 stimulation indicating an inherent cellular defect in energy production. In addition, the spare respiratory capacity (SRC) of GPAT-1 (-/-) CD4+ T cells, a key indicator of their ability to cope with mitochondrial stress was significantly decreased. We also observed a significant reduction in mitochondrial membrane potential in GPAT-1 (-/-) CD4(+) T cells compared to their WT counterparts, indicating that GPAT-1 deficiency results in altered or dysfunctional mitochondria. These data demonstrate that deletion of GPAT-1 can dramatically alter total cellular metabolism under conditions of increased energy demand. Furthermore, altered metabolic response following stimulation may be the defining mechanism underlying T cell dysfunction in GPAT-1 (-/-) CD4(+) T cells. Taken together, these results indicate that GPAT-1 is essential for the response to the increased metabolic demands associated with T cell activation.

Age-related alterations in T-lymphocytes modulate key pathways in prostate tumorigenesis.

BACKGROUND: The primary risk for prostate cancer is aging, often associated with inflammation. Evidence implicates progressive age-related immune dysfunction with increased prostate cancer incidence and mortality. The aged T-cell response is characterized by increased production of pro-inflammatory cytokines, which could significantly contribute to prostate tumorigenesis through induction of key inflammation-mediated pro-survival factors. METHODS: T-cell function of the young (<6 month-old) glycerol-3-phosphate acyltransferase-1 (GPAT-1) knock-out mouse mimics many of the hallmarks observed in an aged (>22-month-old) mouse. Serum and splenic T-lymphocytes from young GPAT-1(-/-) (6 months) and aged wild type (22 months) mice were collected for in vitro studies, including a cytokine immunoarray for serum cytokine levels, luciferase assays for NF-κB activation and Western blot analyses for protein expression. RESULTS: The T-cell cytokine profile of the GPAT-1(-/-) mice mirrored that observed in aged wild type mice, including higher expression levels of IL-17. Serum- and T-cell-derived factors induced NF-κB activity in normal, non-transformed and prostate cancer epithelial cells, correlating with re-localization of NF-κB and increased protein expression of downstream targets of NF-κB. CONCLUSION: The aging and aging-mimic mice produced circulating factors that induce pro-inflammatory pathways in prostate cells, most notably NF-κB. These findings provide evidence that an aged T-cell may directly contribute to the increased risk for prostate cancer in the elderly and establish that the GPAT-1(-/-) model, which mimics many of the characteristics of an aged immune system, is a viable tool for investigating this novel area of cancer risk.

Hepatic lipid metabolism changes in short- and long-term prehepatic portal hypertensive rats.

AIM: To verify the impairment of the hepatic lipid metabolism in prehepatic portal hypertension. METHODS: The concentrations of free fatty acids, diacylglycerol, triglycerides, and phospholipids were assayed by using D-[U-14C] glucose incorporation in the different lipid fractions and thin-layer chromatography and cholesterol was measured by spectrophotometry, in liver samples of Wistar rats with partial portal vein ligation at short- (1 mo) and long-term (1 year) (i.e. portal hypertensive rats) and the control rats. RESULTS: In the portal hypertensive rats, liver phospholipid synthesis significantly decreased (7.42 +/- 0.50 vs 4.70 +/- 0.44 nCi/g protein; P < 0.01) and was associated with an increased synthesis of free fatty acids (2.08 +/- 0.14 vs 3.36 +/- 0.33 nCi/g protein; P < 0.05), diacylglycerol (1.93 +/- 0.2 vs 2.26 +/- 0.28 nCi/g protein), triglycerides (2.40 +/- 0.30 vs 4.49 +/- 0.15 nCi/g protein) and cholesterol (24.28 +/- 2.12 vs 57.66 +/- 3.26 mg/g protein; P < 0.01). CONCLUSION: Prehepatic portal hypertension in rats impairs the liver lipid metabolism. This impairment consists in an increase in lipid deposits (triglycerides, diacylglycerol and cholesterol) in the liver, accompanied by a decrease in phospholipid synthesis.