A Theory of Change for One-on-One Peer support for older adolescents and young adults

Peer support has become increasingly available as a formal mental health service. However, high quality research and implementation of peer support has been hampered over the years by the lack of theory that clarifies peer support roles and explains exactly how these roles foster positive outcomes for peer support users. Observers have noted that theory is particularly sparse in regard to peer support for older adolescents and young adults, and they have called for theory that not only clarifies roles and mechanisms of impact, but also identifies how peer support for young people might differ from peer support for older adults This qualitative study brought young people with experience providing and using peer support together in small group discussions focused on understanding the activities and outcomes of peer support. This information was used to develop a theory of change that outlines key activities that constitute a one-on-one peer support role for young people, and describes how and why carrying out these activities should lead to positive outcomes. The theory highlights the characteristics of a successful “peerness-based relationship,” and proposes that the development of this kind of relationship mediates other positive outcomes from peer support. The article concludes with a discussion of how this theory can usefully inform the development and specification of peer support roles, training and supervision, and other organizational supports

Rho-associated kinase (ROCK) function is essential for cell cycle progression, senescence and tumorigenesis

Rho-associated kinases 1 and 2 (ROCK1/2) are Rho-GTPase effectors that control key aspects of the actin cytoskeleton, but their role in proliferation and cancer initiation or progression is not known. Here, we provide evidence that ROCK1 and ROCK2 act redundantly to maintain actomyosin contractility and cell proliferation and that their loss leads to cell-cycle arrest and cellular senescence. This phenotype arises from down-regulation of the essential cell-cycle proteins CyclinA, CKS1 and CDK1. Accordingly, while the loss of either Rock1 or Rock2 had no negative impact on tumorigenesis in mouse models of non-small cell lung cancer and melanoma, loss of both blocked tumor formation, as no tumors arise in which both Rock1 and Rock2 have been genetically deleted. Our results reveal an indispensable role for ROCK, yet redundant role for isoforms 1 and 2, in cell cycle progression and tumorigenesis, possibly through the maintenance of cellular contractility

Role of Cyclin B1/Cdc2 Up-Regulation in the Development of Mitotic Prometaphase Arrest in Human Breast Cancer Cells Treated with Nocodazole

Background: During a normal cell cycle, the transition from G 2 phase to mitotic phase is triggered by the activation of the cyclin B1-dependent Cdc2 kinase. Here we report our finding that treatment of MCF-7 human breast cancer cells with nocodazole, a prototypic microtubule inhibitor, results in strong up-regulation of cyclin B1 and Cdc2 levels, and their increases are required for the development of mitotic prometaphase arrest and characteristic phenotypes. Methodology/Principal Findings: It was observed that there was a time-dependent early increase in cyclin B1 and Cdc2 protein levels (peaking between 12 and 24 h post treatment), and their levels started to decline after the initial increase. This early up-regulation of cyclin B1 and Cdc2 closely matched in timing the nocodazole-induced mitotic prometaphase arrest. Selective knockdown of cyclin B1or Cdc2 each abrogated nocodazole-induced accumulation of prometaphase cells. The nocodazole-induced prometaphase arrest was also abrogated by pre-treatment of cells with roscovitine, an inhibitor of cyclin-dependent kinases, or with cycloheximide, a protein synthesis inhibitor that was found to suppress cyclin B1 and Cdc2 up-regulation. In addition, we found that MAD2 knockdown abrogated nocodazole-induced accumulation of cyclin B1 and Cdc2 proteins, which was accompanied by an attenuation of nocodazole-induced prometaphase arrest. Conclusions/Significance: These observations demonstrate that the strong early up-regulation of cyclin B1 and Cdc2 contributes critically to the rapid and selective accumulation of prometaphase-arrested cells, a phenomenon associate

A study of Docetaxel-induced effects in MCF-7 cells by means of Raman microspectroscopy

Chemotherapies feature a low success rate of about 25%, and therefore, the choice of the most effective cytostatic drug for the individual patient and monitoring the efficiency of an ongoing chemotherapy are important steps towards personalized therapy. Thereby, an objective method able to differentiate between treated and untreated cancer cells would be essential. In this study, we provide molecular insights into Docetaxel-induced effects in MCF-7 cells, as a model system for adenocarcinoma, by means of Raman microspectroscopy combined with powerful chemometric methods. The analysis of the Raman data is divided into two steps. In the first part, the morphology of cell organelles, e.g. the cell nucleus has been visualized by analysing the Raman spectra with k-means cluster analysis and artificial neural networks and compared to the histopathologic gold standard method hematoxylin and eosin staining. This comparison showed that Raman microscopy is capable of displaying the cell morphology; however, this is in contrast to hematoxylin and eosin staining label free and can therefore be applied potentially in vivo. Because Docetaxel is a drug acting within the cell nucleus, Raman spectra originating from the cell nucleus region were further investigated in a next step. Thereby we were able to differentiate treated from untreated MCF-7 cells and to quantify the cell–drug response by utilizing linear discriminant analysis models

Lysophosphatidate Induces Chemo-Resistance by Releasing Breast Cancer Cells from Taxol-Induced Mitotic Arrest

Taxol is a microtubule stabilizing agent that arrests cells in mitosis leading to cell death. Taxol is widely used to treat breast cancer, but resistance occurs in 25-69% of patients and it is vital to understand how Taxol resistance develops to improve chemotherapy. The effects of chemotherapeutic agents are overcome by survival signals that cancer cells receive. We focused our studies on autotaxin, which is a secreted protein that increases tumor growth, aggressiveness, angiogenesis and metastasis. We discovered that autotaxin strongly antagonizes the Taxol-induced killing of breast cancer and melanoma cells by converting the abundant extra-cellular lipid, lysophosphatidylcholine, into lysophosphatidate. This lipid stimulates specific G-protein coupled receptors that activate survival signals.In this study we determined the basis of these antagonistic actions of lysophosphatidate towards Taxol-induced G2/M arrest and cell death using cultured breast cancer cells. Lysophosphatidate does not antagonize Taxol action in MCF-7 cells by increasing Taxol metabolism or its expulsion through multi-drug resistance transporters. Lysophosphatidate does not lower the percentage of cells accumulating in G2/M by decreasing exit from S-phase or selective stimulation of cell death in G2/M. Instead, LPA had an unexpected and remarkable action in enabling MCF-7 and MDA-MB-468 cells, which had been arrested in G2/M by Taxol, to normalize spindle structure and divide, thus avoiding cell death. This action involves displacement of Taxol from the tubulin polymer fraction, which based on inhibitor studies, depends on activation of LPA receptors and phosphatidylinositol 3-kinase.This work demonstrates a previously unknown consequence of lysophosphatidate action that explains why autotaxin and lysophosphatidate protect against Taxol-induced cell death and promote resistance to the action of this important therapeutic agent

Understanding Individual and Family Experiences Associated with DUP: Lessons from the Early Assessment and Support Alliance (EASA) Program in Oregon, USA

Research shows that a longer duration of untreated psychosis (DUP) is associated with worse psychiatric outcomes, with average length of DUP of 73 weeks in the U.S. The aim was to examine the DUP period for first episode psychosis in Oregon, with a focus on the processes between the first positive symptoms and first treatment. To investigate DUP, researchers used methods consistent with grounded theory to collect data from 9 participants and their families about the process between onset of psychotic symptoms and entrance into treatment. Results suggest that recognition of symptoms was the primary driver of help-seeking in this study, and this was influenced by type of symptom as well as the presence or absence of supportive others, which in most cases was regular family contact. Implications indicate a need for in-depth research on individual and family recognition of symptoms, as well as underscoring the need for community education

On the Cusp: Pathways to Employment, Education, and Disability in First-Episode Psychosis (FEP)

Thesis (Ph.D.)--University of Washington, 2019Poverty is a persistent problem in serious mental illness (SMI) with adult unemployment rates consistently hovering around 80%. A psychiatric paradigm shift toward early intervention for first-episode psychosis (FEP) has shown promise in supporting employment and education in early stages of treatment, but with mixed outcomes. Theories implicate existing low SES and its associated structural barriers, social drift into disability following onset in early adulthood, and disability status with its accompanying label and stigma, in the maintenance of poverty for this population. Utilizing life course theory and considering that the developmental period before disability is established is a particularly critical intervention point for poverty prevention among this group, it is an urgent research priority to learn how young adults with FEP negotiate employment and/or education and how interventions can facilitate this process. This dissertation explored the ways in which employment, education, or disability trajectories form during the early stages of living with a FEP. Utilizing a standpoint epistemological lens, which seeks to highlight the position of the marginalized, 19 interviews were conducted with a critical case sample of young adults with lived experience of a FEP and early intervention programs to explore the key moments, messages, and structural influences that determined their trajectories towards employment, education, or disability. Results indicate that the initial life disruption from a FEP in young adulthood leads to a suspension of gainful activity, followed by a period of forward progress through overcoming their early experiences with hospitalization and medication regimes, and adjusting their self-concept after the label of psychosis. Mental health professionals sent different messages about disability or capability depending on treatment ideology, while families provided varying levels of support and encouragement based on their own SES and subsequent values. Finally, young adults who were successful in entering the labor market did so by moving into direct career pathways instead of looking for work in the secondary labor market, utilized university disability centers, and found support and direction through their involvement with the council. These conclusions have significant implications for early intervention programs, including targeting early-onset FEP, shifting employment focus to the primary labor market, promoting adjunctive peer-based support, and challenging the professional mental health discourse about disability. Implications for research include the need to better understand the pathways of FEP young adults who are not in education, employment, or training (NEET) and who face additional barriers to accessing employment programs and the labor market