Self-concealment, secrecy, and guilt.

OBJECTIVE: Individuals with a tendency to conceal unflattering information about themselves are more likely to be preoccupied by their secrets and tend to report more negative affect. According to theory, this negative affect is due to self-concealers' conflicting motivation to be authentic in their relationship but fear the negative consequences should they reveal their secrets, which promotes ill-fated attempts to suppress. The purpose of the current study was to test a central component of this model. METHODS: Two studies of adults who were in a romantic relationship and keeping a secret from their partner (combined N = 635; 67.2% women; Mage  = 39.6, SD = 11.9) were surveyed on four biweekly occasions. Multilevel mediation analyses were conducted to test whether preoccupation and suppression mediated the link between self-concealing and negative affect and guilt. RESULTS: The data support the hypotheses. Self-concealers were more preoccupied with and prone to suppress their secret than those low on the trait, which, in turn, predicted greater negative affect and guilt. CONCLUSION: The findings suggest that self-concealers' insecurities and fear of the relational consequences of disclosure set the stage for the debilitating cycle of suppression and preoccupation that leaves them feeling anxious and guilty.

Player-Facing Casino Employees: Engagement with Responsible Gambling Programming and its Association with Referring Players.

This research explores the engagement of player-facing casino employees with GameSense, a responsible gambling (RG) program, and referral of players to GameSense. We surveyed 280 employees across three casinos in Massachusetts that use this RG program as part of their RG strategy. We found that although most player-facing casino employees were aware of GameSense, slightly over half visited a GameSense Information Center, and about two-thirds interacted with a GameSense Advisor. In terms of the reason for visiting, Latent Class Analysis (LCA) revealed three distinct classes: Comprehensive Interests, RG Interests, and Focused Interests. As for those who have yet to visit, LCA two classes emerged: RG Proficiency Beliefs and Tempered RG Proficiency Beliefs. Engaged employees were more likely to refer players to GameSense, highlighting the need for targeted approaches addressing the diverse interests of player-facing employees for engaging or not engaging with GameSense. These findings underscore the importance of have player-facing casino employees engage with RG programming, and targeted approached for engagement, to enhance the efficacy of RG initiatives, and contribute to a more robust RG framework within the gambling industry.

Mindfulness-based stress reduction and cognitive function among breast cancer survivors: A randomized controlled trial.

BACKGROUND: Breast cancer (BC) survivors frequently report changes in cognition after chemotherapy. Mindfulness may benefit survivors by mitigating cancer-related cognitive impairment. As part of a larger study investigating the effects of mindfulness-based stress reduction (MBSR) for BC survivors living with neuropathic pain, the authors assessed whether MBSR would have an effect on cognitive outcomes. METHODS: Participants were randomized to an MBSR intervention group (n = 30) or a waitlist control group (n = 30). Cognitive assessments were administered at 3 time points: at baseline, 2 weeks, and 3 months post-MBSR in the intervention group and at equivalent time intervals for the control group. Multilevel models were used to assess whether MBSR significantly improved task performance at each time point. RESULTS: MBSR participants showed a significantly greater reduction in prospective and retrospective memory failures at 2 weeks postintervention. No effects of MBSR were noted for objective assessments. CONCLUSIONS: These results suggest that MBSR training reduces subjective (but not objective) memory-related impairments in BC survivors who receive treatment with chemotherapy. This study provides insight into a noninvasive intervention to ameliorate memory difficulties in BC survivors.

A Rapamycin-Activated Caspase 9-Based Suicide Gene.

Engineered T cell therapies show considerable promise in the treatment of refractory malignancies. Given the ability of engineered T cells to engraft and persist for prolonged periods along with unpredicted toxicities, incorporation of a suicide gene to allow selective depletion after administration is desirable. Rapamycin is a safe and widely available immunosuppressive pharmaceutical that acts by heterodimerization of FKBP12 with the FRB fragment of mTOR. The apical caspase caspase 9 is activated by homodimerization through its CARD domain. We developed a rapamycin-induced caspase 9 suicide gene. First, we showed that caspase 9 could be activated by a two-protein format with replacement of the CARD domain with both FRB and FKBP12. We next identified an optimal compact single-protein rapamycin caspase 9 (rapaCasp9) by fusing both FRB and FKBP12 with the catalytic domain of caspase 9. Functionality of rapaCasp9 when co-expressed with a CD19 CAR was demonstrated in vitro and in vivo.

The Dark Side of Authenticity: Feeling "Real" While Gambling Interacts with Enhancement Motives to Predict Problematic Gambling Behavior.

Engaging in activities that make people feel authentic or real is typically associated with a host of positive psychological and physiological outcomes (i.e., being authentic serves to increase well-being). In the current study, we tested the idea that authenticity might have a dark side among people engaged in an addictive or risky behavior (gambling). To test this possibility, we assessed gamblers (N = 61) who were betting on the National Hockey League playoff games at a sports bar. As predicted, people who felt authentic when gambling reported behavior associated with problem gambling (high frequency of betting) as well as problematic play (a big monetary loss and a big monetary win). Moreover, such behavior and gambling outcomes were particularly high among people who were motivated to gamble for the purpose of enhancement. The interaction of feeling authentic when betting and gambling for purposes of enhancing positive emotions proved especially troublesome for problematic forms of play. Implications of authenticity as a potential vulnerability factor for sports betting and other types of gambling are discussed.

Participation and well-being poststroke: evidence of reciprocal effects.

OBJECTIVE: To explore reciprocal effects between participation and emotional and physical well-being during the first 2 years poststroke. DESIGN: Prospective cohort study. SETTING: Community. PARTICIPANTS: An inception cohort of adults (N=67) who had been discharged from an acute stroke unit or stroke rehabilitation unit after a first stroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participation (Reintegration to Normal Living Index), emotional well-being (General Well-being Schedule), and physical well-being (General Self-rating of Health Question) were measured at 6, 9, 12, 18, and 24 months poststroke. Hierarchical linear modeling was used to examine the association between participation and change in well-being, controlling for sex, age, impairment (discharge FIM), and median neighborhood income. RESULTS: Greater engagement in valued activities was significantly associated with subsequent improvement in emotional well-being. The effect of participation on change in physical well-being was marginal. Higher levels of well-being also predicted subsequent increases in participation, with emotional well-being effects moderated by income, and physical well-being effects moderated by level of impairment. CONCLUSIONS: Our results support a 2-pronged approach to addressing well-being poststroke where efforts to improve affect and boost participation are simultaneously applied.

TLR3 agonist improves survival to secondary pneumonia in a double injury model.

BACKGROUND: Toll-like receptors (TLR) can initiate various immune responses and are therefore activated under diverse infectious states. Previous studies have focused on TLR3 primarily as an antiviral pathway. However, recent research has demonstrated its efficacy in bacterial infection. Having developed a murine double injury model of cecal ligation and puncture (CLP) followed by Pseudomonas aeruginosa (Pa), we hypothesized that targeted administration of Poly I:C, a TLR3 agonist, would protect mice against secondary pneumonia. MATERIAL AND METHODS: B6 mice underwent CLP followed 4 d afterward by an intranasal dose of Pa. Animals were given Poly I:C or vehicle (phosphate-buffered saline) intranasally 24 h post CLP and every day thereafter for a total of 6 d. For acute studies, mice were sacrificed at two time points, 4 d post CLP and 1 d post pneumonia (Pa). RESULTS: Poly I:C treatment led to a significant improvement in survival (69% versus 33%). Cytokine analysis from bronchioalveolar lavage displayed significant differences both immediately before and after pneumonia. Bronchioalveolar lavage cultures taken at 24 h post double injury showed significantly higher colony counts in the lungs of control animals compared with those of Poly I:C animals. Measurements of TLR3 expression showed significant increases within both the immune and lung epithelial cells of Poly I:C-treated mice. Finally, the lungs of treated animals had significant increases in lymphocytes and innate cells. CONCLUSIONS: The prophylactic treatment applied in this clinically relevant model further illustrates the overarching hypothesis of immune dysfunction and the possibility of corrective immune modulation within the setting of sepsis.

Community peer support among individuals living with spinal cord injury.

Peer support is widely assumed to help individuals with spinal cord injury (SCI) adjust, yet the evidence is mixed. We propose that peer support may be more likely to promote adjustment when informal support is lacking. To test this hypothesis, 135 individuals living with SCI receiving peer support (46.7% female; Mage = 42.36, SD = 14.83) completed an online survey assessing aspects of and satisfaction with the peer support and family/friend support that they were receiving as well as measures of adjustment. Although those reporting receiving more peer support were not any better adjusted than those reporting less, individuals who were more satisfied with the peer support they received reported better adjustment. Moreover, the relation of satisfaction with peer support with depressive symptoms was dependent on the level of family/friend support. These findings suggest that peer support is most effective among those lacking support from family and friends.

IL-15 prevents apoptosis, reverses innate and adaptive immune dysfunction, and improves survival in sepsis.

IL-15 is a pluripotent antiapoptotic cytokine that signals to cells of both the innate and adaptive immune system and is regarded as a highly promising immunomodulatory agent in cancer therapy. Sepsis is a lethal condition in which apoptosis-induced depletion of immune cells and subsequent immunosuppression are thought to contribute to morbidity and mortality. This study tested the ability of IL-15 to block apoptosis, prevent immunosuppression, and improve survival in sepsis. Mice were made septic using cecal ligation and puncture or Pseudomonas aeruginosa pneumonia. The experiments comprised a 2 x 2 full factorial design with surgical sepsis versus sham and IL-15 versus vehicle. In addition to survival studies, splenic cellularity, canonical markers of activation and proliferation, intracellular pro- and antiapoptotic Bcl-2 family protein expression, and markers of immune cell apoptosis were evaluated by flow cytometry. Cytokine production was examined both in plasma of treated mice and splenocytes that were stimulated ex vivo. IL-15 blocked sepsis-induced apoptosis of NK cells, dendritic cells, and CD8 T cells. IL-15 also decreased sepsis-induced gut epithelial apoptosis. IL-15 therapy increased the abundance of antiapoptotic Bcl-2 while decreasing proapoptotic Bim and PUMA. IL-15 increased both circulating IFN-gamma, as well as the percentage of NK cells that produced IFN-gamma. Finally, IL-15 increased survival in both cecal ligation and puncture and P. aeruginosa pneumonia. In conclusion, IL-15 prevents two immunopathologic hallmarks of sepsis, namely, apoptosis and immunosuppression, and improves survival in two different models of sepsis. IL-15 represents a potentially novel therapy of this highly lethal disorder.

Finding meaning in a traumatic loss: a families approach.

Meaning-making, like much of coping research, has been conceptualized and assessed as an individual-centered phenomenon. On the premise that most traumas affect families as a whole, we assessed the extent to which meanings following a traumatic loss were congruent within families. Qualitative and quantitative data from family members coping with the loss of a family member in a mine explosion indicated moderate family congruence in meanings and global well-being. Furthermore, greater family similarity in meaning was associated with less depressive affect in individuals (pseudo R(2) = .063), but was not associated with individual differences in well-being. The research highlights the important role that families play in coping with trauma.

Increased susceptibility to Candida infection following cecal ligation and puncture.

Secondary infection following septic insult represents a significant cause of morbidity and mortality in hospitalized patients. Sepsis induced immunosuppression is a major factor in the host's susceptibility to nosocomial infections and Candida albicans accounts for a growing number of these. Given the importance of improving our understanding of the immune response to sepsis and the increasing rates of C. albicans infections, we sought to develop a murine model of double injury consisting of primary peritonitis, i.e., cecal ligation and puncture (CLP), followed by a secondary challenge of C. albicans. As observed in previous work, after primary injury the immune profile of the host changes over time. Therefore, while keeping the mortality rates from the respective individual injuries low, we altered the timing of the secondary injury between two post-CLP time points, day two and day four. Mice subjected to C. albicans infection following CLP have significantly different survival rates dependent upon timing of secondary injury. Animals challenged with C. albicans at two days post CLP had 91% mortality whereas animals challenged at four days had 47% mortality. This improvement in survival at four days was associated with restoration of innate cell populations and as evidenced by stimulated splenocytes, increases in certain inflammatory cytokines. In addition, we show that susceptibility to C. albicans infection following CLP is dependent upon the depth of immunosuppression. Although at four days post-CLP there is a partial reconstitution of the immune system, these animals remain more susceptible to infection compared to their single injury (C. albicans alone) counterparts. Collectively, these studies demonstrate that immunosuppression following initial septic insult changes over time. This novel, two hit model of CLP followed by Candida provides additional insight into the immune compromised state created by primary peritonitis, and thereby opens up another avenue of investigation into the causes and possible cures of an emerging clinical problem.

Factors promoting greater preoccupation with a secret.

The secrets that are most taxing to one's health and well-being are those that are the most preoccupying to the secret-keeper. However, it is currently unclear what makes a secret preoccupying. We conducted a four-wave longitudinal study to assess four factors that should contribute to one's degree of preoccupation with a secret kept from one's spouse/romantic partner: perceived cost of revealing the secret, frequency of cues, fear of discovery, and individual differences in self-concealment. Multilevel modelling of data from an online sample of 143 adults (51% women, 49% men; Mage  = 39.9, SD = 9.3) keeping a secret from their spouse/partner indicated that all four factors independently and positively predict greater preoccupation with a secret. Further, the first three factors also significantly predicted how preoccupied one would be with one's secret two weeks later, taking into account how preoccupied one was with the secret at present. We conclude that the characteristics of the secret, as well as the secret-keeper, can contribute to how preoccupying a secret is to an individual.

Secrets, Psychological Health, and the Fear of Discovery.

Keeping secrets from one's partner has been associated with lower well-being and relationship satisfaction. Previous research has suggested that individual differences in self-concealment account for these effects. However, we propose that the fear of discovery (FoD)-defined as the fear that one's secret may be revealed by means other than deliberate disclosure-predicts the extent to which secrets affect well-being beyond the effects attributable to individual differences. Both a cross-sectional and a longitudinal survey (combined N = 471; 54.4% female; Mage = 39.5) of adults in romantic relationships confirmed that FoD predicted greater preoccupation with the secret, more negative affect, and less relationship satisfaction and commitment beyond that of self-concealment. Multilevel modeling in Study 2 indicated that changes in FoD predicted changes in preoccupation over time. The data are consistent with the notion that FoD promotes greater preoccupation, greater negative affect, and lower levels of relationship well-being.

On being loyal to a casino: The interactive influence of tier status and disordered gambling symptomatology on attitudinal and behavioral loyalty.

BACKGROUND AND AIMS: Casino loyalty programs are marketing strategies designed to foster attitudinal (i.e., identification and satisfaction) and behavioral (i.e., spending) loyalty among gamblers by offering rewards to members. Casino loyalty programs use a tier-based structure to segment members who spend more money into higher tiers, where they receive better rewards (compared to lower tiered members). Tier-based structures may encourage increased expenditure among patrons, especially among players living with a gambling disorder. The current work aimed to examine whether tier status and disordered gambling symptomatology interact to predict attitudinal and behavioral loyalty. METHODS: Study 1 used a cross-sectional design to examine whether tier status and disordered gambling symptomatology interact to predict self-reported loyalty among a sample of American casino loyalty program members (N = 396). In Study 2, archival player account data from Canadian casino loyalty program members (N = 649) were analyzed to examine whether tier status and disordered gambling symptomatology interact to predict objective measures of behavioral loyalty. RESULTS: The greatest effect of tier status on attitudinal and behavioral loyalty was observed among non-problem gamblers in the highest tiers. Tier status, however, did not influence loyalty among members high in disordered gambling symptomatology. DISCUSSION: Results suggest that once gambling has become problematic, loyalty programs may not influence player attitudes and behaviors. Non-problem gamblers may be particularly susceptible to the tiered structure of the programs. CONCLUSION: Non-problem gamblers may benefit from casino loyalty programs in the short-term but longitudinal research is needed to understand the long-term influence of membership.

Characterization and modulation of the immunosuppressive phase of sepsis.

Sepsis continues to cause significant morbidity and mortality in critically ill patients. Studies of patients and animal models have revealed that changes in the immune response during sepsis play a decisive role in the outcome. Using a clinically relevant two-hit model of sepsis, i.e., cecal ligation and puncture (CLP) followed by the induction of Pseudomonas aeruginosa pneumonia, we characterized the host immune response. Second, AS101 [ammonium trichloro(dioxoethylene-o,o')tellurate], a compound that blocks interleukin 10 (IL-10), a key mediator of immunosuppression in sepsis, was tested for its ability to reverse immunoparalysis and improve survival. Mice subjected to pneumonia following CLP had different survival rates depending upon the timing of the secondary injury. Animals challenged with P. aeruginosa at 4 days post-CLP had approximately 40% survival, whereas animals challenged at 7 days had 85% survival. This improvement in survival was associated with decreased lymphocyte apoptosis, restoration of innate cell populations, increased proinflammatory cytokines, and restoration of gamma interferon (IFN-gamma) production by stimulated splenocytes. These animals also showed significantly less P. aeruginosa growth from blood and bronchoalveolar lavage fluid. Importantly, AS101 improved survival after secondary injury 4 days following CLP. This increased survival was associated with many of the same findings observed in the 7-day group, i.e., restoration of IFN-gamma production, increased proinflammatory cytokines, and decreased bacterial growth. Collectively, these studies demonstrate that immunosuppression following initial septic insult increases susceptibility to secondary infection. However, by 7 days post-CLP, the host's immune system has recovered sufficiently to mount an effective immune response. Modulation of the immunosuppressive phase of sepsis may aid in the development of new therapeutic strategies.

Sepsis induces extensive autophagic vacuolization in hepatocytes: a clinical and laboratory-based study.

Autophagy is the regulated process cells use to recycle nonessential, redundant, or inefficient components and is an adaptive response during times of stress. In addition to its function in enabling the cell to gain vital nutrients in times of stress, autophagy can also be involved in elimination of intracellular microorganisms, tumor suppression, and antigen presentation. Because of difficulty in diagnosing autophagy, few clinical studies have been performed. This study examined whether autophagy occurs in hepatocytes during sepsis. Electron microscopy (EM) was performed on liver samples obtained from both an observational clinical cohort of six septic patients and four control patients as well as liver specimens from mice with surgical sepsis (by cecal ligation and puncture) or sham operation. EM demonstrated increased autophagic vacuoles in septic vs nonseptic patients. Randomly selected fields (3000 microm(2)) from control and septic patients contained 1.2+/-1.5 vs 5.3+/-3.3 (mean+/-s.d.) complex lysosomal/autophagolysosomal structures per image respectively (P<0.001). In rare instances, hepatocytes with autophagic vacuoles appeared to be unequivocally committed to death. Membrane alterations (membrane vacuoles, invagination into adjacent organelles, and myelin figure-like changes) occur in a subpopulation of mitochondria in sepsis, but other hepatocyte organelles showed no consistent ultrastructural injury. Findings in murine sepsis paralleled those of patients, with 7.2+/-1.9 vs 38.7+/-3.9 lysosomal/autophagolysosomal structures in sham and septic mice, respectively (P=0.002). Quantitative RT-PCR demonstrated that sepsis induced the upregulation of select apoptosis and cytokine gene expression with minimal changes in the core autophagy genes in liver. In conclusion, hepatocyte autophagic vacuolization increases during sepsis and is associated with mitochondrial injury. However, it is not possible to determine whether the increase in autophagic vacuolization is an adaptive response or a harbinger of cell death.

An anti-apoptotic peptide improves survival in lethal total body irradiation.

Cell penetrating peptides (CPPs) have been used to deliver the anti-apoptotic Bcl-xL-derived BH4 peptide to prevent injury-induced apoptosis both in vitro and in vivo. Here we demonstrate that the nuclear localization sequence (NLS) from the SV40 large T antigen has favorable properties for BH4 domain delivery to lymphocytes compared to sequences based on the HIV-1 TAT sequence. While both TAT-BH4 and NLS-BH4 protected primary human mononuclear cells from radiation-induced apoptotic cell death, TAT-BH4 caused persistent membrane damage and even cell death at the highest concentrations tested (5-10 microM) and correlated with in vivo toxicity as intravenous administration of TAT-BH4 caused rapid death. The NLS-BH4 peptide has significantly attenuated toxicity compared to TAT-BH4 and we established a dosing regimen of NLS-BH4 that conferred a significant survival advantage in a post-exposure treatment model of LD90 total body irradiation.

Effects of aging on the immunopathologic response to sepsis.

OBJECTIVE: Aging is associated with increased inflammation following sepsis. The purpose of this study was to determine whether this represents a fundamental age-based difference in the host response or is secondary to the increased mortality seen in aged hosts. DESIGN: Prospective, randomized controlled study. SETTING: Animal laboratory in a university medical center. SUBJECTS: Young (6-12 weeks) and aged (20-24 months) FVB/N mice. INTERVENTIONS: Mice were subjected to 2 x 25 or 1 x 30 cecal ligation and puncture (CLP). MEASUREMENTS AND MAIN RESULTS: Survival was similar in young mice subjected to 2 x 25 CLP and aged mice subjected to 1 x 30 CLP (p = 0.15). Young mice subjected to 1 x 30 CLP had improved survival compared with the other groups (p < 0.05). When injury was held constant but mortality was greater, both systemic and peritoneal levels of tumor necrosis factor-alpha, interleukin (IL)-6, IL-10, and monocyte chemotactic protein-1 were elevated 24 hours after CLP in aged animals compared with young animals (p < 0.05). When mortality was similar but injury severity was different, there were no significant differences in systemic cytokines between aged mice and young mice. In contrast, peritoneal levels of tumor necrosis factor-alpha, IL-6, and IL-10 were higher in aged mice subjected to 1 x 30 CLP than young mice subjected to 2 x 25 CLP despite their similar mortalities (p < 0.05). There were no significant differences in either bacteremia or peritoneal cultures when animals of different ages sustained similar injuries or had different injuries with similar mortalities. CONCLUSIONS: Aged mice are more likely to die of sepsis than young mice when subjected to an equivalent insult, and this is associated with increases in both systemic and local inflammation. There is an exaggerated local but not systemic inflammatory response in aged mice compared with young mice when mortality is similar. This suggests that systemic processes that culminate in death may be age independent, but the local inflammatory response may be greater with aging.

Deletion of MyD88 markedly attenuates sepsis-induced T and B lymphocyte apoptosis but worsens survival.

Sepsis induces widespread lymphocyte apoptosis, resulting in impaired immune defenses and increased morbidity and mortality. There are multiple potential triggers or signaling molecules involved in mediating death signals. Elucidating the specific signaling pathways that are involved in mediating lymphocyte apoptosis may lead to improved therapies of this lethal disorder. We investigated a number of key cellular receptors and intracellular signaling pathways that may be responsible for apoptotic cell death. Specifically, we investigated the role of pathogen-associated molecular patterns (TLR2, TLR4, and IL-1R), intracellular signaling proteins (MyD88 and TRIF), cytoplasmic transcription factors (STAT1 and STAT4), and the MAPK pathway (JNK1) in sepsis-induced lymphocyte apoptosis. Studies were performed in the cecal ligation and puncture (CLP) model of sepsis using specific gene-targeted deletions. CLP-induced lymphocyte apoptosis was evaluated 20 h post-operation by active caspase-3 and TUNEL staining. Surprisingly, the only genetic construct that ameliorated T and B lymphocyte sepsis-induced apoptosis ( approximately 80% and 85%, respectively) occurred in MyD88(-/-) mice. Despite the marked decrease in sepsis-induced apoptosis, MyD88(-/-) mice had a worsened survival. In conclusion, lymphocyte death in sepsis likely involves multiple pathogen-sensing receptors and redundant signaling pathways. MyD88 was effective in blocking apoptosis, as it is essential in mediating most pathogen recognition pathways; however, MyD88 is also critical for host survival in a model of severe peritonitis.

Effects of weight teasing and gender on body esteem in youth: A longitudinal analysis from the REAL study.

Weight teasing is associated with body dissatisfaction, but no study has examined the differential impact of the teasing source's gender. This study examined whether the longitudinal relationship between weight teasing (by peers), weight-related comments (by parents) and body esteem differed by the teasing sources' gender, and whether these relationships were moderated by victims' weight status and demographic factors. A school-based sample (N = 1197 at Time 1; 60% female) of adolescents completed surveys over approximately 2 years (Time 1-Time 3). Multilevel modeling showed that teasing from a male peer had a stronger, negative association with appearance esteem for female victims than males. Although weight teasing was more prevalent among youth with overweight/obesity, teasing from female peers had a stronger negative association with weight esteem for adolescents of average weight. Results suggest the weight teasing sources' gender may differentially impact the victims' body esteem, and highlights the need to consider these factors in weight teasing prevention strategies.