The Impact of Relationship Separation on Suicidality and Mental Health

Introduction: Relationship separation is common and can be a significant risk factor for suicidal thoughts and behaviours. However, there exists a paucity of research that explores the relationship between suicidality and separation, and even less focusing on accessible interventions for separated individuals. Methods: A systematic review was conducted to establish the impact of intimate partner relationships on suicidality, specifically how relationship separation contributes to suicidal thoughts and behaviours. An online cross-sectional survey was developed to explore potential predictors of suicidality and to identify challenges, benefits and help-seeking strategies following a relationship separation. A final systematic review was conducted to assess the impact of existing separation interventions on mental health, specifically focusing on suicidal thoughts and behaviours. The results from these studies guided the development of MindCast, a six-session, online podcast program based on Brief Interpersonal Psychotherapy (IPT-B), designed for people who have separated from a relationship. The effectiveness of this intervention was evaluated through a randomised controlled trial of 124 Australian participants who had separated in the last six months. Results: The results of the systematic reviews highlighted that relationship separation and poor quality relationships are likely to be important risk factors for suicidal thoughts and behaviours and are a frequent trigger for a suicide attempt. However, there exists a paucity of trials that adequately assess the effects of non-marital relationship separation interventions on mental health outcomes and none that consider suicidal thoughts and/or behaviours. The cross-sectional study identified greater symptoms of antagonism and disinhibition and less active coping, decreased positive family support, less negative friends and lower self-esteem as being significantly associated with increased odds of suicidal ideation. Qualitative analyses revealed that males were significantly more likely to report “no benefit” to the separation, compared with females who were significantly more likely to report “leaving an abusive and/or negative relationship” and “moving on” as benefits to the relationship break-up. Although the MindCast intervention did not have a significant effect on depression or suicidal ideation, across time, between group effects sizes (post, d = 0.50 and follow-up, d = 0.10) indicated that the MindCast intervention may have the potential to decrease depressive symptoms in people who have separated from a relationship, compared to a control condition. Low post-intervention (n = 30) and follow-up (n = 20) response rates were a primary limitation. Conclusion: The MindCast podcast represents the first self-directed, online podcast developed for people who have separated from an intimate partner relationship. It was also the first study of its kind to adapt IPT, of any form, to a podcast format and to explore the influence of such an intervention on suicidal ideation and broader psychosocial targets. Although the results did not indicate that the intervention was effective in terms of targeting primary mental health outcomes, qualitative feedback suggests that participants were keen to engage in the content. Further, the small to moderate between group effect sizes were encouraging and suggest that significant effects may be observed in an adequately powered trial. Research focusing on suicide prevention and early intervention is needed to continue to identify risk factors and key intervention areas

Detection and Functional Characterization of a 215 Amino Acid N-Terminal Extension in the Xanthomonas Type III Effector XopD

During evolution, pathogens have developed a variety of strategies to suppress plant-triggered immunity and promote successful infection. In Gram-negative phytopathogenic bacteria, the so-called type III protein secretion system works as a molecular syringe to inject type III effectors (T3Es) into plant cells. The XopD T3E from the strain 85-10 of Xanthomonas campestris pathovar vesicatoria (Xcv) delays the onset of symptom development and alters basal defence responses to promote pathogen growth in infected tomato leaves. XopD was previously described as a modular protein that contains (i) an N-terminal DNA-binding domain (DBD), (ii) two tandemly repeated EAR (ERF-associated amphiphillic repression) motifs involved in transcriptional repression, and (iii) a C-terminal cysteine protease domain, involved in release of SUMO (small ubiquitin-like modifier) from SUMO-modified proteins. Here, we show that the XopD protein that is produced and secreted by Xcv presents an additional N-terminal extension of 215 amino acids. Closer analysis of this newly identified N-terminal domain shows a low complexity region rich in lysine, alanine and glutamic acid residues (KAE-rich) with high propensity to form coiled-coil structures that confers to XopD the ability to form dimers when expressed in E. coli. The full length XopD protein identified in this study (XopD1-760) displays stronger repression of the XopD plant target promoter PR1, as compared to the XopD version annotated in the public databases (XopD216-760). Furthermore, the N-terminal extension of XopD, which is absent in XopD216-760, is essential for XopD type III-dependent secretion and, therefore, for complementation of an Xcv mutant strain deleted from XopD in its ability to delay symptom development in tomato susceptible cultivars. The identification of the complete sequence of XopD opens new perspectives for future studies on the XopD protein and its virulence-associated functions in planta

A Systematic Review of Controlled Trials Evaluating Interventions Following Non-Marital Relationship Separation

The effect of a relationship separation on wellbeing is substantial. However, without divorce parameters, individuals in dating or cohabiting relationships may struggle to access support mechanisms. A systematic review was conducted to identify controlled trials of interventions targeting individuals who have experienced a non-marital relationship separation, to supplement the divorce literature. The aim of the review was to assess the impact of these interventions on mental health. Five articles were identified through PsycINFO, PsycARTICLES and Medline databases. Overall, two of the trials reported a significant improvement in specific mental health outcomes at post-test and/or follow-up. Of the two trials demonstrating efficacy in mental health outcomes, one used a weekly, forgiveness-based group intervention and the other was a writing-based, self-initiated intervention. A lack of trials testing theory-driven interventions for relationship separation is of particular concern. Limitations of the existing literature and corresponding directions for future research are discussed.This research and DK are supported by the National Health and Medical Research Council (NHMRC) Centre of Research Excellence in Suicide Prevention (1042580). PJB and ALC are supported by National Health and Medical Research Council (NHMRC) fellowships 1083311 and 1013199

Study of the microRNA expression profile of foreskin derived mesenchymal stromal cells following inflammation priming

Background: Due to their self-renewal capacity, multi-lineage potential, and immunomodulatory properties, mesenchymal stromal cells (MSCs) are an attractive tool for different therapeutic strategies. Foreskin (FSK), considered as a biological waste material, has already been shown to be a valuable source of MSCs. Besides their typical fibroblast like morphology and International Society for cellular Therapy compliant phenotype, foreskin-MSCs (FSK-MSCs) are clonogenic, and highly proliferative cells with multi-lineage and strong immunomodulatory capacities. Of importance, FSK-MSCs properly adjust their fate following exposure to inflammatory signals. Being potent regulators of gene expression, miRNAs are involved in modulating nearly all cellular processes and in orchestrating the roles of different immune cells. In this study, we characterized the miRNome of FSK-MSCs by determining the expression profile of 380 different miRNAs in inflammation primed vs. control non-primed cells. Methods: TaqMan low density array (TLDA) was performed to identify dysregulated miRNAs after exposing FSK-MSCs to inflammatory signals. Quantitative real-time RT-PCR was carried out to validate the observations. DIANA-miRPath analysis web server was used to identify potential pathways that could be targeted by the dysregulated miRNAs. Results: Sixteen miRNAs were differentially expressed in inflammation-primed vs. non-primed FSK-MSCs. The expression level of miR-27a, -145, -149, -194, -199a, -221, -328, -345, -423-5p, -485-3p, -485-5p, -615-5p and -758 was downregulated whilst that of miR-155, -363 and -886-3p was upregulated. Target pathway prediction of those differentially expressed miRNAs identified different inflammation linked pathways. Conclusions: After determining their miRNome, we identified a striking effect of inflammatory signals on the miRNAs' expression levels in FSK-MSCs. Our results highlight a potential role of miRNAs in modulating the transcription programs of FSK-MSCs in response to inflammatory signals. Further, we propose that specific miRNAs could serve as interesting targets to manipulate some functions of FSK-MSCs, thus ameliorating their therapeutic potential.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Data on nitric oxide production by human bone marrow-derived mesenchymal stromal cells

Due to its anti-inflammatory and immunosuppressive potential, Nitric oxide (NO), a gaseous radical, is of special importance during graft-versus-host diseases (GVHD) and feoto-maternal tolerance. NO is a major mediator of murine mesenchymal stromal cells (MSCs)-immunosuppressive capacity. In this data article, we characterized NO production by human bone marrow-derived MSCs (hBMSCs). MSCs, isolated from healthy donors (n=5), were defined according to the International Society for cellular Therapy (ISCT) guidelines. Based on a fluorometric detection system, and upon using Nitrite (NO2−)/Nitrate ( NO3−) Assay Kit, the amounts of NO metabolites ( NO2− and NO3−) produced by hBMSCs, being grown in a culture medium either lacking (constitutive condition) or containing IL-4, IL-10 or a pro-inflammatory cytokine cocktail made of IL-1β, TNF-α, IFN-α and IFN-γ, were assessed. All assays were carried out in triplicates and the mean values are reported. The data from this study supports and corroborates the discussion associated with our previously published work entitled “The Immunomodulatory Potential of Mesenchymal Stromal Cells: A Story of a Regulatory Network” (Najar et al., 2016) [1]

Mesenchymal stromal cells of the bone marrow and natural killer cells: cell interactions and cross modulation.

Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are multipotent progenitor cells that have shown promise for several different therapeutic applications. As they are able to modulate the function of several types of immune cells, BM-MSCs are highly important in the field of cell-based immunotherapy. Understanding BM-MSC-natural killer (NK) cell interactions is crucial for improving their therapeutic efficiency. Here, we observed that the type of NK cell-activating cytokine (e.g. IL-2, IL-12, IL-15 and IL-21) strongly influenced the outcomes of their interactions with BM-MSCs. The expression patterns of the ligands (CD112, CD155, ULPB-3) and receptors (LAIR, NCR) mediating the cross-talk between BM-MSCs and NK cells were critically modulated following co-culture. BM-MSCs partially impaired NK cell proliferation but up-regulated their secretion of IFN-γ and TNF-α. As they are cytotoxic, activated NK cells induced the killing of BM-MSCs. Indeed, BM-MSCs triggered the degranulation of NK cells and increased their release of perforin and granzymes. Interestingly, activated NK cells induced ROS generation within BM-MSCs that caused their decreased viability and reduced expression of serpin B9. Collectively, our observations reveal that BM-MSC-NK cell interactions may impact the immunobiology of both cell types. The therapeutic potential of BM-MSCs will be significantly improved once these issues are well characterized.info:eu-repo/semantics/publishe

Immunological impact of Wharton's Jelly mesenchymal stromal cells and natural killer cell co-culture.

Due to their easier isolation, multilineage potential, and immunomodulatory capacity, Wharton's Jelly-derived mesenchymal stromal cells (WJ-MSCs) exhibit promising efficacy in the field of regenerative medicine and immunotherapy. Characterization of WJ-MSCs-natural killer (NK) cells crosstalk is required for ameliorating the medicinal value of WJ-MSCs. Here, we revealed that the outcome of WJ-MSCs-NK cells crosstalk varied according to the type of cytokines (IL-2, IL-12, IL-15 and IL-21) utilized to activate NK cells. Differently activated NK cells exerted distinct cytotoxicities against WJ-MSCs causing their probable death. Cell surface ligands (CD112, CD155, ULPB-3) and receptors (LAIR, CD226, CD314, CD335, CD336 and CD337) governing the interaction between NK cells and their targets, exhibited altered expression profiles following the co-culture with WJ-MSCs. Although partly inhibited NK cell proliferation, WJ-MSCs enhanced activated NK-cell-mediated secretion of IFN-γ and TNF-α. Moreover, WJ-MSCs reinforced NK cells' degranulation as well as secretion of perforin and granzymes. On the other hand, WJ-MSCs displayed only slight increase in ROS generation but significant decrease in A1 and C1 serpins expression following co-culture with activated NK cells. Altogether, our results highlight that WJ-MSCs-NK cells interaction may affect both cell type features and, therefore, their therapeutic properties.info:eu-repo/semantics/publishe

Immunomodulatory effects of foreskin mesenchymal stromal cells (FSK-MSCs) on natural killer (NK) cells.

Foreskin-mesenchymal stromal cells (FSK-MSCs) are immune-privileged thus making them valuable immunotherapeutic cell product. Characterization of the relationship between FSK-MSCs and natural killer (NK) cells is essential to improve cell-based therapy. In the present study, we studied for the first time FSK-MSCs-NK interaction and showed that the result of such cross talk was robustly dependent on the type of cytokines (IL-2, IL-12, IL-15 and IL-21) employed to activate NK cells. Distinctly activated-NK cells showed uneven cytotoxicity against FSK-MSCs, triggering their death in fine. The expression of different cell-surface ligands (CD112, CD155, ULPB-3) and receptors (LAIR, KIRs) ensuring such interaction was altered following co-culture of both populations. Despite their partial negative effect on NK cell proliferation, FSK-MSCs boosted the capacity of activated NK-cells to secrete IFN-γ and TNF-α. Moreover, FSK-MSCs enhanced degranulation of NK cells, reinforced secretion of perforin and granzymes, whilst only modestly increased ROS production. On the other hand, FSK-MSCs-mediated expression of C1 and B9 serpins was significantly lowered in the presence of activated NK cells. Altogether, our results highlight major immunological changes following FSK-MSCs-NK interaction. Understanding these outcomes will therefore enhance the value of the therapeutic strategy. This article is protected by copyright. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Differences in mental health service use between urban and rural areas of Australia

Objective: To examine differences in use of mental health services between residents of rural, regional, and metropolitan areas of Australia in a population-based sample of adults who meet clinical criteria for a mental disorder. Method: Participants in this study were drawn from the Assessing Mental Health survey, which included 2,374 participants who met criteria for one or more mental disorders or reported suicidal ideation in the past month. Rates of self-reported use of specific services for mental health problems (doctor/general practitioner, social worker, hospital, psychologist, psychiatrist, or counsellor) were compared between areas of residence, with subsequent logistic regression analyses used to account for potential confounds for variations in service use. Results: There were no differences in overall rates of use of professional services for mental health problems. There were also no significant differences in help seeking from specific sources, with the exception of psychologists. People in rural areas were 26% less likely to report having sought help from a psychologist in the past year than those in metropolitan areas (18% vs. 24%). This discrepancy was not accounted for by stigma, but attenuated after adjustment for severity of psychological distress and demographic factors. Conclusion: Little evidence of differences in help seeking in rural Australia compared to urban centres was observed, with the important exception of psychological service use. Further research is needed to characterise disparities in quality and accessibility of care.Calvert Jones Foundation; Ian Potter Foundation; Medical Research Future Fund, Grant/Award Number: 1150698; National Health and Medical Research Council, Grant/Award Numbers: 1043952, 115870