Current challenges in understanding immune cell functions during septic syndromes.

BACKGROUND: Sepsis is a dynamic infectious disease syndrome characterized by dysregulated inflammatory responses. RESULTS: Despite decades of research, improvements in the treatment of sepsis have been modest. These limited advances are likely due, in part, to multiple factors, including substantial heterogeneity in septic syndromes, significant knowledge gaps in our understanding of how immune cells function in sepsis, and limitations in animal models that accurately recapitulate the human septic milieu. The goal of this brief review is to describe current challenges in understanding immune cell functions during sepsis. We also provide a framework to guide scientists and clinicians in research and patient care as they strive to better understand dysregulated cell responses during sepsis. CONCLUSIONS: Additional, well-designed translational studies in sepsis are critical for enhancing our understanding of the role of immune cells in sepsis.

Platelet-monocyte aggregate formation and mortality risk in older patients with severe sepsis and septic shock.

BACKGROUND: Aging-related changes in platelet and monocyte interactions may contribute to adverse outcomes in sepsis but remain relatively unexamined. We hypothesized that differential platelet-monocyte aggregate (PMA) formation in older septic patients alters inflammatory responses and mortality. METHODS: We prospectively studied 113 septic adults admitted to the intensive care unit with severe sepsis or septic shock. Patients were dichotomized a priori into one of two groups: older (age ≥ 65 years, n = 28) and younger (age < 65 years, n = 85). PMA levels were measured in whole blood via flow cytometry within 24 hours of admission. Plasma levels of IL-6 and IL-8, proinflammatory cytokines produced by monocytes upon PMA formation, were determined by commercial assays. Patients were followed for the primary outcome of 28-day, all-cause mortality. RESULTS: Elevated PMA levels were associated with an increased risk of mortality in older septic patients (hazard ratio for mortality 5.64, 95% confidence interval 0.64-49.61). This association remained after adjusting for potential confounding variables in multivariate regression. Receiver operating curve analyses demonstrated that PMA levels greater than or equal to 8.43% best predicted 28-day mortality in older septic patients (area under the receiver operating curve 0.82). Plasma IL-6 and IL-8 levels were also significantly higher in older nonsurvivors. In younger patients, neither PMA levels nor plasma monokines were significantly associated with mortality. CONCLUSIONS: Increased PMA formation, and associated proinflammatory monokine synthesis, predicts mortality in older septic patients. Although larger studies are needed, our findings suggest that heightened PMA formation in older septic patients may contribute to injurious inflammatory responses and an increased risk of mortality.

Posttraumatic stress disorder and responses to couple conflict: implications for cardiovascular risk.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is associated with increased risk of coronary heart disease (CHD) and difficulties in intimate relationships. Greater frequency and severity of couple conflict and greater cardiovascular reactivity to such conflict might contribute to CHD risk in those with PTSD, but affective and physiological responses to couple conflict have not been examined previously in this population. METHOD: In a preliminary test of this hypothesis, 32 male veterans of the Iraq and Afghanistan Wars with PTSD and their female partners, and 33 control male veterans without PTSD and their female partners completed relationship quality assessments and a conflict discussion task. PTSD diagnosis was confirmed through diagnostic interviews and questionnaires. State anger, state anxiety, and cardiovascular measures (i.e., blood pressure, heart rate) were recorded during baseline and the conflict discussion. RESULTS: Compared with controls, PTSD couples reported greater couple conflict and less warmth, and displayed pronounced increases in anger and greater increases in systolic blood pressure in response to the conflict task (all ps < .05; range η2: .05-.24). Partners in the PTSD group exhibited similar, if not greater, responses as veterans. CONCLUSIONS: This was the first investigation to document emotional and cardiovascular responses to couple conflict in veterans with PTSD and their partners. PTSD was associated with greater frequency and severity of couple conflict, and greater anger and cardiovascular reactivity to conflict discussions. Anger and physiological responses to couple discord might contribute to CHD risk in veterans with PTSD, and perhaps their partners, as well.

Communication behaviors and patient and caregiver emotional concerns: a description of home hospice communication.

PURPOSE/OBJECTIVES: To identify and describe communication behaviors used by hospice nurses when eliciting and addressing concerns of patients with cancer and their caregivers. DESIGN: Secondary analysis. SETTING: Home hospice in Salt Lake City, UT. SAMPLE: Audio recordings from seven patient and caregiver dyads and five hospice nurses. METHODS: Audio recordings were coded using the Roter Interaction Analysis System for patient and caregiver concern statements indicating negative affect and distress and the surrounding nurse communication behaviors. Concern content was categorized using domains developed by the National Consensus Project for Quality Palliative Care. MAIN RESEARCH VARIABLES: Patient and caregiver concern statements and nurse communication behaviors. FINDINGS: 180 patient and caregiver speaking turns containing concerns were identified across 31 hospice visits. Patients and caregivers expressed at least one concern in the vast majority of visits. The most prevalent distress areas reflected psychological and physical issues. Nurses used proportionally more positive emotion statements before patient and caregiver concerns, compared to the visit overall. Nurses asked proportionally more physical questions after concern statements. Nurses also used more emotional responses before and after patient and caregiver concerns, relative to the entire visit. CONCLUSIONS: Patients with cancer and caregivers frequently talk about distressing issues. Hospice nurses use specific communication behaviors to elicit and address those issues. IMPLICATIONS FOR NURSING: Home hospice provides a venue to examine nurse communication behaviors used to elicit and respond to patient and caregiver distress. These strategies could be taught to nurses who encounter patient distress less frequently or are less comfortable with emotional conversations.

Alterations in platelet function during aging: clinical correlations with thromboinflammatory disease in older adults.

Platelets have a dynamic functional repertoire that mediates hemostatic and inflammatory responses. Many of these functions are altered in older adults, promoting a prothrombotic, proinflammatory milieu and contributing to risk of adverse clinical events. Drawing primarily from human studies, this review summarizes important aspects of aging-related changes in platelets. The relationship between altered platelet functions and thrombotic and inflammatory disorders in older adults is highlighted. Established and developing antiplatelet therapies for the treatment of thrombotic and inflammatory disorders are also discussed in light of these data.

Cellular aging and restorative processes: subjective sleep quality and duration moderate the association between age and telomere length in a sample of middle-aged and older adults.

STUDY OBJECTIVES: To examine whether subjective sleep quality and sleep duration moderate the association between age and telomere length (TL). DESIGN: Participants completed a demographic and sleep quality questionnaire, followed by a blood draw. SETTING: Social Neuroscience Laboratory. PARTICIPANTS: One hundred fifty-four middle-aged to older adults (age 45-77 y) participated. Participants were excluded if they were on immunosuppressive treatment and/or had a disease with a clear immunologic (e.g., cancer) component. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Subjective sleep quality and sleep duration were assessed using the Pittsburgh Sleep Quality Index (PSQI) and TL was determined using peripheral blood mononuclear cells (PBMCs). There was a significant first-order negative association between age and TL. Age was also negatively associated with the self-reported sleep quality item and sleep duration component of the PSQI. A significant age × self-reported sleep quality interaction revealed that age was more strongly related to TL among poor sleepers, and that good sleep quality attenuated the association between age and TL. Moreover, adequate subjective sleep duration among older adults (i.e. greater than 7 h per night) was associated with TL comparable to that in middle-aged adults, whereas sleep duration was unrelated to TL for the middle-aged adults in our study. CONCLUSIONS: The current study provides evidence for an association between sleep quality, sleep duration, and cellular aging. Among older adults, better subjective sleep quality was associated with the extent of cellular aging, suggesting that sleep duration and sleep quality may be added to a growing list of modifiable behaviors associated with the adverse effects of aging.

The stress-buffering effects of functional social support on ambulatory blood pressure.

OBJECTIVE: Social support is a reliable predictor of cardiovascular health. According to the buffering hypothesis, stress is 1 mechanism by which support is able to affect physiological processes. However, most of the experimental evidence for the hypothesis comes from laboratory studies. Ambulatory blood pressure (ABP) protocols examine participants in their natural environment, where they are more likely to encounter personally relevant real-world stressors. Furthermore, prior work shows that examining support by its specific functional components reveals additional independent links to health. METHODS: The current study aimed to examine the stress-buffering effects of functional social support on ABP. One hundred eighty-eight participants completed a 1-day ABP assessment along with measures of functional social support and both global perceived stress and momentary stress at time of reading. RESULTS: RESULTS indicated main effects for both stress measures. Global support, emotional, tangible, and informational support only moderated the effects of momentary stress, but not global stress, in predicting ABP. Informational support was the most consistent stress-buffering predictor of ABP, predicting both ambulatory systolic and diastolic blood pressure. CONCLUSIONS: The predicted values in ABP for informational support achieved health-relevant differences, emphasizing the value of examining functional support beyond global support alone.

Relationships and cardiovascular risk: perceived spousal ambivalence in specific relationship contexts and its links to inflammation.

OBJECTIVES: Although perceiving one's social ties as sources of ambivalence has been linked to negative health outcomes, the more specific contexts by which such relationships influence health remain less studied. We thus examined if perceived spousal relationship quality in three theoretically important contexts (i.e., support, capitalization, everyday life) predicted inflammation. METHOD: Ninety-four married couples completed measures of perceived spousal positivity and negativity in support, capitalization, and everyday contexts. These scores were used to derive an index of relationship ambivalence whereby interactions were rated as containing both positive and negative aspects. Serum levels of IL-6, fibrinogen, and CRP were assessed from plasma. RESULTS: Perceiving ambivalence toward one's spouse in a support context was linked to greater inflammation even when considering health behaviors, relationship-specific romantic attachment style, spouse negativity/positivity ratings, and overall marital satisfaction. Perceiving ambivalence toward a spouse during capitalization predicted higher fibrinogen levels only, whereas no links were found with perceived spousal ambivalence in everyday life contexts. CONCLUSION: Perceptions of ambivalence during support may be a particularly important relational context in which marital ties influence health.

The quality of spouses' social networks contributes to each other's cardiovascular risk.

OBJECTIVES: Although the quality of one's own social relationships has been related to cardiovascular morbidity and mortality, whether a partner's social network quality can similarly influence one's cardiovascular risk is unknown. In this study we tested whether the quality of a partner's social networks influenced one's own ambulatory blood pressure (ABP). METHODS: The quality of 94 couples' social networks was determined using a comprehensive model of relationships that separates out social ties that are sources of positivity(supportive), negativity (aversive), and both positivity and negativity (ambivalent). We then utilized statistical models (actor-partner analyses) that allowed us to separate out the links between one's own social network quality on ABP (actor influences), a partner's social network quality on ABP (partner influences), and a couple's network quality combined on ABP (actor X partner interactions). RESULTS: Independent of one's own relationship quality, results showed that an individual's ABP was lower if their spouse had more supportive ties, and higher if a spouse had more aversive and ambivalent ties. In addition, couples' networks in combination were associated with higher ABP but only if both had a low number of supportive ties, or a high number of aversive or ambivalent ties. CONCLUSIONS: These data suggest that the social ties of those we have close relationships with may influence our cardiovascular risk and opens new opportunities to capitalize on untapped social resources or to mitigate hidden sources of social strain.

Specific dimensions of perceived support and ambulatory blood pressure: which support functions appear most beneficial and for whom?

Perceived support has been related to lower cardiovascular morbidity and mortality. However, little is known about the specific functional components of support responsible for such links. We tested if emotional, informational, tangible, and belonging support predicted ambulatory blood pressure (ABP) and interpersonal interactions (e.g., responsiveness), and if such links were moderated by gender. In this study, 94 married couples underwent 12 h of ABP monitoring during daily life which included a night at home with their spouse. They completed a short-form of the interpersonal support evaluation list that provides information on total (global) support, as well as specific dimensions of support. Results revealed that global support scores did not predict ABP during daily life. However, separating out distinct support components revealed that emotional support was a significant predictor of lower ambulatory systolic and diastolic blood pressure, primarily for women. Finally, emotional support predicted greater partner responsiveness and self-disclosure, along with less perceived partner negativity although these results were not moderated by gender. These data are discussed in terms of the importance of considering specific support components and the contextual processes that might influence such links.

Psychological pathways linking social support to health outcomes: a visit with the "ghosts" of research past, present, and future.

Contemporary models postulate the importance of psychological mechanisms linking perceived and received social support to physical health outcomes. In this review, we examine studies that directly tested the potential psychological mechanisms responsible for links between social support and health-relevant physiological processes (1980s-2010). Inconsistent with existing theoretical models, no evidence was found that psychological mechanisms such as depression, perceived stress, and other affective processes are directly responsible for links between support and health. We discuss the importance of considering statistical/design issues, emerging conceptual perspectives, and limitations of our existing models for future research aimed at elucidating the psychological mechanisms responsible for links between social support and physical health outcomes.

Social relationships and health: is feeling positive, negative, or both (ambivalent) about your social ties related to telomeres?

OBJECTIVES: The quality of one's personal relationships has been linked to morbidity and mortality across different diseases. As a result, it is important to examine more integrative mechanisms that might link relationships across diverse physical health outcomes. In this study, we examine associations between relationships and telomeres that predict general disease risk. These questions are pursued in the context of a more comprehensive model of relationships that highlights the importance of jointly considering positive and negative aspects of social ties. METHOD: One hundred thirty-six individuals from a community sample (ages 48 to 77 years) completed the social relationships index, which allows a determination of relationships that differ in their positive and negative substrates (i.e., ambivalent, supportive, aversive, indifferent). Telomere length was determined from peripheral blood mononuclear cells via quantitative polymerase chain reaction. RESULTS: Participants who had a higher number of ambivalent ties in their social networks evidenced shorter telomeres. These results were independent of other relationship types (e.g., supportive) and standard control variables (e.g., age, health behaviors, and medication use). Gender moderated the links between ambivalent ties and telomere length, with these associations seen primarily in women. Follow-up analyses revealed that the links between ambivalent ties and telomeres were primarily due to friendships, parents, and social acquaintances. CONCLUSION: Consistent with epidemiological findings, these data highlight a novel and integrative biological mechanism by which social ties may affect health across diseases and further suggest the importance of incorporating positivity and negativity in the study of specific relationships and physical health.

Subliminal activation of social ties moderates cardiovascular reactivity during acute stress.

OBJECTIVE: The quality of one's personal relationships has been reliably linked to important physical health outcomes, perhaps through the mechanism of physiological stress responses. Most studies of this mechanism have focused on whether more conscious interpersonal transactions influence cardiovascular reactivity. However, whether such relationships can be automatically activated in memory to influence physiological processes has not been determined. The primary aims of this study were to examine whether subliminal activation of relationships could influence health-relevant physiological processes and to examine this question in the context of a more general relationship model that incorporates both positive and negative dimensions. METHOD: We randomly assigned participants to be subliminally primed with existing relationships that varied in their underlying positivity and negativity (i.e., indifferent, supportive, aversive, ambivalent). They then performed acute psychological stressors while cardiovascular and self-report measures were assessed. RESULTS: Priming negative relationships was associated with greater threat, lower feelings of control, and higher diastolic blood pressure reactivity during stress. Moreover, priming relationships high in positivity and negativity (ambivalent ties) was associated with the highest heart rate reactivity and greatest respiratory sinus arrhythmia decreases during stress. Exploratory analyses during the priming task itself suggested that the effects of negative primes on biological measures were prevalent across tasks, whereas the links to ambivalent ties was specific to the subsequent stressor task. CONCLUSIONS: These data highlight novel mechanisms by which social ties may impact cardiovascular health, and further suggest the importance of incorporating both positivity and negativity in the study of relationships and physical health.

Social support and the reactivity hypothesis: conceptual issues in examining the efficacy of received support during acute psychological stress.

Social support has been reliably related to better physical health outcomes. One influential model suggests that social support is related to lower cardiovascular disease mortality because it reduces the potentially deleterious consequences of cardiovascular reactivity during acute stress. However, received support and perceived support are separable constructs and epidemiological research suggests variability in links between received support and health. This is important because most social support and acute laboratory stress studies are essentially based on the receipt of support. In this paper, we focus on the conceptualization of received support and its implications for understanding links to support laboratory reactivity paradigms. This analysis highlights the role of theoretically important task, recipient, and provider categories of factors that moderate the effectiveness of received support, as well as the need to examine links between naturalistic perceptions of support and cardiovascular reactivity during stress.