'It's Nothing Like Cancer': Young Adults with Cancer Reflect on Memorable Entertainment Narratives.

A cancer diagnosis in young adulthood disrupts the achievement of developmental milestones, and young adults struggle to make sense of their cancer experience due to a lack of opportunities to both openly talk about cancer and engage in reflective activities. However, entertainment narratives - or stories - may be an alternative to prompt these activities, as narratives can elicit self-expansion that may help fulfill intrinsic needs. One way to think about these narratives is as memorable messages. These messages stick with a person for a long period of time, have an anticipatory socialization effect, and may prompt the sense-making process through narrative communication. Little is known, though, about the use of entertainment narratives among young adults with cancer. We interviewed 25 young adults with cancer about entertainment narratives that were memorable during their cancer experience and how those narratives affected them. From these in-depth, semi-structured interviews, we found that entertainment narratives were generally helpful if they provided distraction from cancer, were relatable, and/or prompted participants to explore their emotions. We found that entertainment narratives were generally harmful if they worsened participants' emotional state, either by exacerbating fears of death and/or depicting cancer unrealistically. Our findings suggest that entertainment narratives are memorable messages, and that helpful messages increased feelings of competence and validation, which could promote psychological adaptation to the disease. Harmful messages increased fear and invalidated participants' difficult experiences, which could lead to greater illness centrality and internalized stigma. Implications for future research are discussed.

Using Social Media for Peer-to-Peer Cancer Support: Interviews With Young Adults With Cancer.

BACKGROUND: Web-based social support can address social isolation and unmet support needs among young adults with cancer (aged 18-39 years). Given that 94% of young adults own and use smartphones, social media can offer personalized, accessible social support among peers with cancer. OBJECTIVE: This study aims to examine the specific benefits, downsides, and topics of social support via social media among young adults with cancer. METHODS: We conducted semistructured interviews with young adults with cancer, aged between 18 and 39 years, who were receiving treatment or had completed treatment for cancer. RESULTS: Most participants (N=45) used general audience platforms (eg, Facebook groups), and some cancer-specific social media (eg, Caring Bridge), to discuss relevant lived experiences for medical information (managing side effects and treatment uncertainty) and navigating life with cancer (parenting and financial issues). Participants valued socializing with other young adults with cancer, making connections outside their personal networks, and being able to validate their emotional and mental health experiences without time and physical constraints. However, using social media for peer support can be an emotional burden, especially when others post disheartening or harassing content, and can heighten privacy concerns, especially when navigating cancer-related stigma. CONCLUSIONS: Social media allows young adults to connect with peers to share and feel validated about their treatment and life concerns. However, barriers exist for receiving support from social media; these could be reduced through content moderation and developing more customizable, potentially cancer-specific social media apps and platforms to enhance one's ability to find peers and manage groups.

Initiation and changes in use of social media for peer support among young adult cancer patients and survivors.

PURPOSE: Social isolation is a prominent challenge for many young adults with cancer. Despite desires for peer-to-peer connections through technology, little is known about how young adults initiate or use social media for support over time. METHODS: We interviewed young adults with cancer (n = 45; age 18-39, in or post cancer treatment) to explore their initiation of social media for support, changes in use over time, and types of connections sought. RESULTS: Young adults with cancer learn about online support through individual personal recommendations, advocacy organizations, or searching on Google or social media. Most were reluctant to use social media support initially because of feeling overwhelmed-from diagnoses, abundance of online information, or demands of participation-and joined when informational and emotional needs arose. Many wished they had joined earlier. Some participants use social media to make close connections while others simply want to "see" others' shared experiences or crowdsource information. CONCLUSION: Young adults with cancer often haphazardly find online support from personal recommendations or Internet searches. Desires for social media connections are not one-size-fits-all; there are important audience segmentations for the degree and type of peer support. IMPLICATIONS FOR CANCER SURVIVORS: Better promotion of online social support options and benefits-early in one's cancer timeline and systematically through healthcare providers, cancer organizations, or family and friends-could improve access to helpful peer-to-peer support.

The Toll-like receptor 4 agonist monophosphoryl lipid a augments innate host resistance to systemic bacterial infection.

Monophosphoryl lipid A (MPLA) is a Toll-like receptor 4 (TLR4) agonist that is currently used as a vaccine adjuvant in humans. In this study, we evaluated the effect of MPLA treatment on the innate immune response to systemic bacterial infections in mice. Mice treated with MPLA after burn injury showed improved survival and less local and systemic dissemination of bacteria in a model of Pseudomonas aeruginosa burn wound infection. Prophylactic treatment with MPLA significantly enhanced bacterial clearance at the site of infection and reduced systemic dissemination of bacteria despite causing attenuation of proinflammatory cytokine production during acute intra-abdominal infection caused by cecal ligation and puncture. Administration of MPLA at 1 h after CLP also improved bacterial clearance but did not alter cytokine production. MPLA treatment increased the numbers of granulocytes, double-positive myeloid cells, and macrophages at sites of infection and increased the percentage and total numbers of myeloid cells mediating phagocytosis of bacteria. Depletion of Ly6G(+) neutrophils, but not macrophages, eliminated the ability of MPLA treatment to improve bacterial clearance. The immunomodulatory effects of MPLA were absent in TLR4-deficient mice. In conclusion, these studies show that MPLA treatment significantly augments the innate immune response to bacterial infection by enhancing bacterial clearance despite the attenuation of proinflammatory cytokine production. The enhanced bacterial clearance is mediated, in part, by increased numbers of myeloid cells with effective phagocytic functions at sites of infection and is TLR4 dependent.

Mice depleted of alphabeta but not gammadelta T cells are resistant to mortality caused by cecal ligation and puncture.

The present study was undertaken to determine whether the mice depleted of alphabeta or gammadelta T cells show resistance to acute polymicrobial sepsis caused by cecal ligation and puncture (CLP). T-cell receptor beta knockout (betaTCRKO) and T-cell receptor delta knockout (deltaTCRKO) mice were used. An additional group of mice was treated with an antibody against the alphabeta T-cell receptor to induce alphabeta T-cell depletion; a subset of alphabeta T cell-deficient mice was also treated with anti-asialoGM1 to deplete natural killer (NK) cells. The mice underwent CLP and were monitored for survival, temperature, acid-base balance, bacterial counts, and cytokine production. The betaTCRKO mice and the wild-type mice treated with anti-beta T-cell receptor (anti-TCRbeta) antibody showed improved survival after CLP compared with wild-type mice. The treatment of alphabeta T cell-deficient mice with anti-asialoGM1further improved survival after CLP, especially when the mice were treated with imipenem. The improved survival observed in alphabeta T cell-deficient mice was associated with less hypothermia, improved acid-base balance, and decreased production of the proinflammatory cytokines interleukin (IL) 6 and macrophage inflammatory protein (MIP) 2. Compared with wild-type controls, the overall survival was not improved in deltaTCRKO mice. The concentrations of IL-6 and MIP-2 in plasma and cytokine mRNA expression in tissues were not significantly different between wild-type and deltaTCRKO mice. These studies indicate that mice depleted of alphabeta but not of gammadelta T cells are resistant to mortality in an acutely lethal model of CLP. The depletion of NK cells caused further survival benefit in alphabeta T cell-deficient mice. These findings suggest that alphabeta T and NK cells mediate or facilitate CLP-induced inflammatory injury.

Effects of aging on mortality, hypothermia, and cytokine induction in mice with endotoxemia or sepsis.

Aging is accompanied by an altered stress response that underlies increased susceptibility of the elderly patients to physiological stress such as infection and sepsis. In the present study, we investigated the effects of aging on mortality, hypothermia, and cytokine induction in mouse models of intra-abdominal sepsis and endotoxemia. Systemic inflammation associated with either cecal ligation/puncture (CLP) or injection with bacterial endotoxin, lipopolysaccharide (LPS), resulted in a significantly elevated mortality rate in aged (24 months) compared to young (4 months) mice. The aged mice also showed profound hypothermia during these inflammatory stresses; the severity of hypothermia at the early phase of sepsis or endotoxemia could predict the mortality of individual animals. The stress-mediated induction of interleukin-1beta, interleukin-6, and interleukin-10 (IL-1beta, IL-6, and IL-10) in the circulating blood tended to be higher with aging in both CLP and LPS models, and in particular, the induction of IL-6 was significantly augmented with aging. The serum level of IL-6 showed a strong correlation with degrees of hypothermia. In the heart and lungs, the induction of mRNA for IL-6 and IL-10 was also significantly enhanced with aging. These results clearly demonstrate an age-associated increase in mortality, hypothermia, and induction of IL-6 during endotoxemia and sepsis.

A multimeric model for murine anti-apoptotic protein Bcl-2 and structural insights for its regulation by post-translational modification.

A monomeric model for murine antiapoptotic protein Bcl-2 was constructed by comparative modeling with the software suite MPACK (EXDIS/DIAMOD/FANTOM) using human Bcl-xL as a template. The monomeric model shows that murine Bcl-2 is an all alpha-helical protein with a central (helix 5) hydrophobic helix surrounded by amphipathic helices and an unstructured loop of 30 residues connecting helices 1 and 2. It has been previously shown that phosphorylation of Ser 70 located in this loop region regulates the anti-apoptotic activity of Bcl-2. Based on our current model, we propose that this phosphorylation may result in a conformational change that aids multimer formation. We constructed a model for the Bcl-2 homodimer based on the experimentally determined 3D structure of the Bcl-xL: Bad peptide complex. The model shows that it will require approximately a half turn in helix 2 to expose hydrophobic residues important for the formation of a multimer. Helices 5 and 6 of the monomeric subunit Bcl-2 have been proposed to form an ion-channel by associating with helices 5 and 6 of another monomeric subunit in the higher-order complex. In the multimeric model of Bcl-2, helices 5 and 6 of each subunit were placed distantly apart. From our model, we conclude that a global conformational change may be required to bring helices 5 and 6 together during ion-channel formation.

Interferon-gamma production is suppressed in thermally injured mice: decreased production of regulatory cytokines and corresponding receptors.

Thermal injury to 40% or more of the total body surface area poses a significant risk for the development of opportunistic infections that increase complications and mortality. Altered cytokine induction profiles, including suppression of the Th1 cytokines IFN-gamma and IL-12 and elevations in the anti-inflammatory cytokine IL-10, are believed to contribute to burn-associated immunosuppression and the development of sepsis. The specific changes that lead to altered cytokine production following major burns are not known. We examined the effects of burn injuries to 40% of the mouse body surface on IFN-gamma induction in the major IFN-gamma-producing cell types of the spleen. Additionally, effects on key IFN-gamma-regulatory cytokines were examined after bacterial challenge. We report that in vivo induction of IFN-gamma in natural killer lymphocytes is suppressed in burned mice. Splenic IFN-gamma was suppressed at both the mRNA and protein levels. Early suppression was associated with impairments in both the macrophage/dendritic cell and lymphocyte populations, whereas persistent suppression was associated with impaired lymphocyte function and decreased responsiveness to IFN-gamma-inducing factors. IFN-gamma production could be restored by neutralization of the upregulated cytokine IL-10. Induction of the IFN-gamma-inducers IL-15, IL-12, and IL-2 was also impaired after burn injury, whereas IL-18 levels remained unaffected. Exogenous application of these suppressed cytokines to isolated splenocytes did not restore IFN-gamma to sham levels, indicating a loss of responsiveness to these factors. Expression of the IL-2, IL-12, and IL-15 receptors was suppressed after thermal injury. We conclude that burn-associated suppression of IFN-gamma is due to deficient production of inducing factors and their receptors, leading to severe impairments in cellular IFN-gamma induction pathways.