A Web-Based, Positive Emotion Skills Intervention for Enhancing Posttreatment Psychological Well-Being in Young Adult Cancer Survivors (EMPOWER): Protocol for a Single-Arm Feasibility Trial

BACKGROUND: Adolescent and young adult cancer survivors (AYAs) experience clinically significant distress and have limited access to supportive care services. Interventions to enhance psychological well-being have improved positive affect and reduced depression in clinical and healthy populations but have not been routinely tested in AYAs. OBJECTIVE: The aim of this protocol is to (1) test the feasibility and acceptability of a Web-based positive emotion skills intervention for posttreatment AYAs called Enhancing Management of Psychological Outcomes With Emotion Regulation (EMPOWER) and (2) examine proof of concept for reducing psychological distress and enhancing psychological well-being. METHODS: The intervention development and testing are taking place in 3 phases. In phase 1, we adapted the content of an existing, Web-based positive emotion intervention so that it would be suitable for AYAs. EMPOWER targets 8 skills (noticing positive events, capitalizing, gratitude, mindfulness, positive reappraisal, goal setting, personal strengths, and acts of kindness) and is delivered remotely as a 5-week, Web-based intervention. Phase 2 consisted of a pilot test of EMPOWER in a single-arm trial to evaluate feasibility, acceptability, retention, and adherence and to collect data on psychosocial outcomes for proof of concept. In phase 3, we are refining study procedures and conducting a second pilot test. RESULTS: The project was part of a career development award. Pilot work began in June 2015, and data collection was completed in March 2019. The analysis is ongoing, and results will be submitted for publication by May 2020. CONCLUSIONS: If this intervention proves feasible and acceptable, EMPOWER will be primed for a subsequent large, multisite randomized controlled trial. As a scalable intervention, it will be ideally suited for AYA survivors who would otherwise not have access to supportive care interventions to help manage posttreatment distress and enhance well-being. TRIAL REGISTRATION: ClinicalTrials.gov NCT02832154, https://clinicaltrials.gov/ct2/show/NCT02832154. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/1707

Optimizing the measurement of health‐related quality of life in adolescents and young adults with cancer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163469/2/cncr33155.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163469/1/cncr33155_am.pd

Exploring parents’ understandings of their child’s journey into offending behaviours:a narrative analysis

Parents are perhaps the best placed individuals to comment upon their child’s life story, including early life experiences, transitions and their child’s needs. However, research has rarely focussed on the views of parents of young people who have committed serious offences. This research aimed to explore parents’ opinions of which factors may have led to their child becoming involved with the criminal justice system. Interviews were undertaken with six parents who were asked to narrate their child’s life journey into offending behaviours. The data were then analysed using narrative analysis techniques, and a shared story was created which incorporated the main transitional stages in the children’s journeys, as seen by the parents. The findings suggest that it is not just the child, but the whole family who have been in a state of distress throughout the child’s life. Systemic and environmental factors are argued to contribute to this distress, and the use of diagnosis for this population is critically evaluated. The research highlights a life story in which the child’s and family’s distress remains unheard and therefore unresolved. Clinical implications for working with this population are discussed

Enhanced Fusion Pore Expansion Mediated by the Trans-Acting Endodomain of the Reovirus FAST Proteins

The reovirus fusion-associated small transmembrane (FAST) proteins are virus-encoded membrane fusion proteins that function as dedicated cell–cell fusogens. The topology of these small, single-pass membrane proteins orients the majority of the protein on the distal side of the membrane (i.e., inside the cell). We now show that ectopic expression of the endodomains of the p10, p14, and p15 FAST proteins enhances syncytiogenesis induced by the full-length FAST proteins, both homotypically and heterotypically. Results further indicate that the 68-residue cytoplasmic endodomain of the p14 FAST protein (1) is endogenously generated from full-length p14 protein expressed in virus-infected or transfected cells; (2) enhances syncytiogenesis subsequent to stable pore formation; (3) increases the syncytiogenic activity of heterologous fusion proteins, including the differentiation-dependent fusion of murine myoblasts; (4) exerts its enhancing activity from the cytosol, independent of direct interactions with either the fusogen or the membranes being fused; and (5) contains several regions with protein–protein interaction motifs that influence enhancing activity. We propose that the unique evolution of the FAST proteins as virus-encoded cellular fusogens has allowed them to generate a trans-acting, soluble endodomain peptide to harness a cellular pathway or process involved in the poorly understood process that facilitates the transition from microfusion pores to macrofusion and syncytiogenesis

Borderline Personality Disorder Symptoms in College Students: The Complex Interplay between Alexithymia, Emotional Dysregulation and Rumination.

Both Emotional Cascade Theory and Linehan's Biosocial Theory suggest dysregulated behaviors associated with Borderline Personality Disorder (BPD) emerge, in part, because of cycles of rumination, poor emotional recognition and poor emotion regulation. In this study we examined relationships between rumination, alexithymia, and emotion regulation in predicting dysregulated behaviors associated with BPD (e.g. self-harm, substance use, aggression), and explored both indirect and moderating effects among these variables. The sample comprised 2261 college students who completed self-report measures of the aforementioned constructs. BPD symptoms, stress, family psychological illness, and alexithymia exerted direct effects on behaviors. Symptoms had an indirect effect on behaviors through rumination, alexithymia and emotional dysregulation. In addition, the relationship between symptoms and dysregulated behaviors was conditional on level of rumination and alexithymia. Implications for early identification and treatment of BPD and related behaviors in college settings are discussed

A Virus-Encoded Cell–Cell Fusion Machine Dependent on Surrogate Adhesins

The reovirus fusion-associated small transmembrane (FAST) proteins function as virus-encoded cellular fusogens, mediating efficient cell–cell rather than virus–cell membrane fusion. With ectodomains of only ∼20–40 residues, it is unclear how such diminutive viral fusion proteins mediate the initial stages (i.e. membrane contact and close membrane apposition) of the fusion reaction that precede actual membrane merger. We now show that the FAST proteins lack specific receptor-binding activity, and in their natural biological context of promoting cell–cell fusion, rely on cadherins to promote close membrane apposition. The FAST proteins, however, are not specifically reliant on cadherin engagement to mediate membrane apposition as indicated by their ability to efficiently utilize other adhesins in the fusion reaction. Results further indicate that surrogate adhesion proteins that bridge membranes as close as 13 nm apart enhance FAST protein-induced cell–cell fusion, but active actin remodelling is required for maximal fusion activity. The FAST proteins are the first example of membrane fusion proteins that have specifically evolved to function as opportunistic fusogens, designed to exploit and convert naturally occurring adhesion sites into fusion sites. The capacity of surrogate, non-cognate adhesins and active actin remodelling to enhance the cell–cell fusion activity of the FAST proteins are features perfectly suited to the structural and functional evolution of these fusogens as the minimal fusion component of a virus-encoded cellular fusion machine. These results also provide a basis for reconciling the rudimentary structure of the FAST proteins with their capacity to fuse cellular membranes

Analysis of Spatial Point Patterns in Nuclear Biology

There is considerable interest in cell biology in determining whether, and to what extent, the spatial arrangement of nuclear objects affects nuclear function. A common approach to address this issue involves analyzing a collection of images produced using some form of fluorescence microscopy. We assume that these images have been successfully pre-processed and a spatial point pattern representation of the objects of interest within the nuclear boundary is available. Typically in these scenarios, the number of objects per nucleus is low, which has consequences on the ability of standard analysis procedures to demonstrate the existence of spatial preference in the pattern. There are broadly two common approaches to look for structure in these spatial point patterns. First a spatial point pattern for each image is analyzed individually, or second a simple normalization is performed and the patterns are aggregated. In this paper we demonstrate using synthetic spatial point patterns drawn from predefined point processes how difficult it is to distinguish a pattern from complete spatial randomness using these techniques and hence how easy it is to miss interesting spatial preferences in the arrangement of nuclear objects. The impact of this problem is also illustrated on data related to the configuration of PML nuclear bodies in mammalian fibroblast cells

Crosstalk between Medulloblastoma Cells and Endothelium Triggers a Strong Chemotactic Signal Recruiting T Lymphocytes to the Tumor Microenvironment

Cancer cells can live and grow if they succeed in creating a favorable niche that often includes elements from the immune system. While T lymphocytes play an important role in the host response to tumor growth, the mechanism of their trafficking to the tumor remains poorly understood. We show here that T lymphocytes consistently infiltrate the primary brain cancer, medulloblastoma. We demonstrate, both in vitro and in vivo, that these T lymphocytes are attracted to tumor deposits only after the tumor cells have interacted with tumor vascular endothelium. Macrophage Migration Inhibitory Factor (MIF)” is the key chemokine molecule secreted by tumor cells which induces the tumor vascular endothelial cells to secrete the potent T lymphocyte attractant “Regulated upon Activation, Normal T-cell Expressed, and Secreted (RANTES).” This in turn creates a chemotactic gradient for RANTES-receptor bearing T lymphocytes. Manipulation of this pathway could have important therapeutic implications