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Although many emerging adults struggle to gain status and develop social relationships, particularly during the college transition, it remains unclear whether certain personality traits facilitate this transition. Using a longitudinal design, we investigated whether status-related traits-namely, entitlement, intrasexual competitiveness, and dominance-related to the development of status in 91 first-year college students (

Author(s): Kuhlman, Kate R; Robles, Theodore F; Haydon, Marcie D; Dooley, Larissa; Boyle, Chloe C; Bower, Julienne E | Abstract: BackgroundEarly life stress (ELS) has been linked to health disparities across the human lifespan, particularly increased risk for depression and its recurrence. In this study we explore two plausible and competing pathways through which ELS may lead to depression via inflammation.MethodsParticipants (ages 18-22; nn=n41) completed the Early Trauma Inventory as a measure of ELS. Participants then completed consecutive daily diaries of mood and other sickness behavior for the 7ndays prior to and 7ndays after receiving the annual influenza vaccine. Circulating concentrations of plasma interleukin-6 (IL-6) were measured immediately before and 24nhr after vaccination.ResultsELS was not associated with the magnitude of change in IL-6 from pre- to post-vaccine, however, exposure to ELS moderated the association between change in IL-6 from pre- to post-vaccine and changes in both cognitive difficulty and depressed mood. Individuals exposed to greater ELS showed greater psychological sensitivity to increases in IL-6.ConclusionsExposure to ELS may increase sensitivity to peripheral inflammation in the central nervous system. Future studies elaborating on the impact of ELS on the sensitivity of specific neural circuits and cells to inflammation are needed.

[Correction Notice: An Erratum for this article was reported online in Emotion on Sep 5 2019 (see record 2019-52812-001). In the article, two text call outs for figures are incorrect. At the end of the "Negative emotional responses" section under the "Psychological Stress Responses" heading, "(see Figure 7)" should have been deleted. Under the "Negative task-related ruminative thoughts" heading in that same section, "(see Figure 5)" in the first paragraph should be "(see Figure 7)."] Expressing emotions is a common strategy for coping with stress. Yet, little is known about the effects of using this strategy in close relationships, or when and for whom emotional expression is effective. This study examined romantic partner responsiveness and the dispositional tendency to use emotional approach coping (EAC; the processing and expression of emotions) as moderators of the effects of experimentally manipulated emotional expression on stress responses to a laboratory stressor. We brought couples (N = 145) to the lab and randomly assigned 1 partner (the participant) to perform a stressful task. We manipulated whether participants expressed their feelings about the task to their partner (expression vs. no-expression), and whether participants received supportive messages from their partners (as an indicator of partner responsiveness; support vs. no-support). We examined physiological stress responses (cortisol and salivary alpha-amylase [sAA]), negative emotional stress responses (anxiety and self-conscious emotions), and post-task ruminative thoughts. Participants high in EAC showed larger sAA and cortisol responses and reported more negative post-task ruminative thoughts after emotionally expressing to their partners, but partner support mitigated the effect on cortisol. Participants low in EAC showed smaller cortisol responses and reported less negative emotional responses and fewer negative post-task ruminative thoughts after emotionally expressing to their partners. Receiving partner support reduced negative emotional responses for people high in EAC, but increased negative emotional responses for those low in EAC. These results may help explain when and for whom emotional expression is an effective means of coping in the immediate context of a stressor. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Impairments in reality testing are core features of numerous neuropsychiatric conditions. However, relatively few animal models have been developed to assess this critical facet of neuropsychiatric illness, thus impeding our understanding of the underlying central systems and circuits. Using mice in which dominant-negative Disrupted-in-Schizophrenia-1 is expressed throughout central nervous system circuitry (DN-DISC1-PrP), the capacity for an auditory conditioned stimulus (CS) to evoke perceptual processing of an absent sucrose solution was examined. At test, during CS presentations, DN-DISC1-PrP mice consumed more water and displayed a licking profile that is more typically revealed while ingesting a sweet-tasting solution. DN-DISC1-PrP mice also displayed greater c-fos expression in the insular (gustatory) cortex when consuming water in the presence of the CS. This capacity for the CS to more readily substitute for the taste features of the absent sucrose solution in DN-DISC1-PrP mice was attenuated following systemic treatment with the antipsychotic haloperidol. Conversely, social isolation during adolescence promoted the manifestation of these effects. These results provide strong validation for using associative learning procedures to examine dopamine-mediated reality testing associated with insular cortex activation.

Refractory or relapsed diffuse large B-cell lymphoma (DLBCL) often associates with the activated B-cell-like (ABC) subtype and genetic alterations that drive constitutive NF-κB activation and impair B-cell terminal differentiation. Here, we show that DNA damage response by p53 is a central mechanism suppressing the pathogenic cooperation of IKK2ca-enforced canonical NF-κB and impaired differentiation resulting from Blimp1 loss in ABC-DLBCL lymphomagenesis. We provide evidences that the interplay between these genetic alterations and the tumor microenvironment select for additional molecular addictions that promote lymphoma progression, including aberrant coexpression of FOXP1 and the B-cell mutagenic enzyme activation-induced deaminase, and immune evasion through major histocompatibility complex class II downregulation, PD-L1 upregulation, and T-cell exhaustion. Consistently, PD-1 blockade cooperated with anti-CD20-mediated B-cell cytotoxicity, promoting extended T-cell reactivation and antitumor specificity that improved long-term overall survival in mice. Our data support a pathogenic cooperation among NF-κB-driven prosurvival, genetic instability, and immune evasion mechanisms in DLBCL and provide preclinical proof of concept for including PD-1/PD-L1 blockade in combinatorial immunotherapy for ABC-DLBCL.

Previous research has linked exposure to adverse social conditions with DNA damage and accelerated telomere shortening, raising the possibility that chronic stress may impact biological aging pathways, ultimately increasing risk for age-related diseases. Less clear, however, is whether these stress-related effects extend to additional hallmarks of biological aging, including cellular senescence, a stable state of cell cycle arrest. The present study aimed to investigate associations between psychosocial stress and two markers of cellular aging-leukocyte telomere length (LTL) and cellular senescence signal p16INK4a. Seventy-three adults (Mage = 43.0, SD = 7.2; 55% female) with children between 8-13 years of age completed interview-based and questionnaire measures of their exposures to and experiences of stress, as well as daily reports of stress appraisals over an 8-week diary period. Blood samples were used to assess markers of cellular aging: LTL and gene expression of senescent cell signal p16INK4a (CDKN2A). Random effects models covarying for age, sex, ethnicity/race, and BMI revealed that participants with greater chronic stress exposure over the previous 6 months (b = 0.011, p = .04), perceived stress (b = 0.020, p

Effective regulation of the hypothalamic-pituitary-adrenal axis (HPA-axis) has been linked to numerous health outcomes. Within-person variation in diurnal measures of HPA-axis regulation assessed over days, months, and years can range between 50-73% of total variation. In this study of 59 youth (ages 8-13), we quantified the stability of the cortisol awakening response (CAR), the diurnal slope, and tonic cortisol concentrations at waking and bedtime across 8 days (2 sets of 4 consecutive days separated by 3 weeks), 3 weeks, and 3 years. We then compared the stability of these indices across three key developmental factors: age, pubertal status, and sex. Youth provided 4 saliva samples per day (waking, 30 minutes post-waking, before dinner, and before bedtime) for 4 consecutive days during the 3(rd) week of an ongoing 8-week daily diary study. Youth repeated this same sampling procedure 3 weeks and 3 years later. Using multi-level modeling, we computed the amount of variance in diurnal HPA-axis regulation that was accounted for by nesting an individual’s diurnal cortisol indices within days, weeks, or years. Across days, diurnal slope was the most stable index, whereas waking cortisol and CAR were the least stable. All indices except bedtime cortisol were similarly stable when measured across weeks, and all indices were uniformly stable when measured across 3 years. Boys, younger participants, and youth earlier in their pubertal development at study enrollment exhibited greater HPA-axis stability overall compared with females and older, more physically mature participants. We conclude that important within- and between-subjects questions can be answered about health and human development by studying HPA-axis regulation, and selection of the index of interest should be determined in part by its psychometric characteristics. To this end, we propose a decision tree to guide study design for research in pediatric samples by longitudinal timeframe and sample characteristics.

A child's social relationships serve critical functions during development. The interface between a child's social world and their immune system, particularly innate immunity, which helped children survive in the face of infections, nutritional scarcity, and violence throughout human history, is the focus of this Annual Research Review. This article reviews the state of research on social relationships and innate immune inflammation during childhood. Warmth and rejection in childhood social relationships, as well as physical trauma and unpredictable social environments, were not consistently related to circulating inflammatory markers such as interleukin-6 and C-reactive protein during childhood. Instead, links between social environments and inflammation were observed in studies that focus on children with greater background risk factors, such as low family socioeconomic status, family history of mood disorders, or presence of chronic interpersonal stressors combined with acute episodic stressors. In addition, studies on worse childhood social environments and greater inflammation in adulthood were more consistent. Warmth and rejection in the social environment may be related to sensitivity of immune cells to the anti-inflammatory actions of glucocorticoids, though this is primarily observed in adolescent women at risk for depression. Additional mechanistic evidence suggests that greater warmth and less rejection are related to processes that regulate inflammation, including greater expression of the glucocorticoid receptor gene and lower expression of genes that are responsive to the pro-inflammatory transcription factor NF-kappa B. The article concludes by discussing implications of the interface between a child's social relationships and inflammation for mental health and other recent (on evolutionary timescales) health threats, as well as recommendations for future research, and recommendations for researchers interested in integrating inflammatory measures in developmental research.

The mental health toll of common school problems that many children encounter every day is not well understood. This study examined individual differences in mood reactivity to naturally occurring school problems using daily diaries, and assessed their prospective associations with youth mental health, three years later. At baseline, 47 children ages 8 to 13 years described common problems at school and mood on a daily basis, for 8 weeks. Thirty-three youth returned for follow-up three years later at ages 11 to 17 years. Children and parents also completed one-time questionnaires about youth mental health at baseline and follow-up. There were individual differences in the within-person associations between school problems and same-day and next-day mood. A greater tendency to react to school problems with more negative mood or less positive mood on the same day predicted more parent-rated internalizing and externalizing problems and child ratings of depression symptoms three years later, relative to baseline levels of symptoms. Daily diaries can help to identify specific targets of psychosocial interventions in real world settings.

Generativity, or concern for and contribution to the well-being of younger generations, plays an important role in successful aging. The purpose of this study was to develop a novel, writing-based intervention to increase feelings of generativity and test the effect of this intervention on well-being and inflammation in a sample of older women. Participants in this study (n=73; mean age = 70.9 years, range 60–86 years) were randomly assigned to a 6-week generativity writing condition (writing about life experiences and sharing advice with others) or a control writing condition (neutral, descriptive writing). Self-reported measures of social well-being, mental health, and physical health, as well as objective measures of systemic and cellular levels of inflammation (plasma pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-α; genome-wide RNA transcriptional profiling), were assessed pre- and post-intervention. The generativity intervention led to significant improvements across multiple domains, including increases in participation in social activities, decreases in psychological distress, more positive expectations regarding aging in the physical health domain, and decreases in pro-inflammatory gene expression. Thus, this study provides preliminary evidence for the ability of a novel, low-cost, low-effort intervention to favorably impact inflammation and well-being in older women. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov

The study of immune and inflammatory markers in saliva has gained increased attention in recent years with the advancements in assay technology and a heightened focus on cross-systems biology and psychoneuroimmunology. Salivary immune markers are important for the study of both oral and systemic health. Salivary inflammation, in particular, has been widely examined across many fields as both an area of interest and a source of confounding variance. In this chapter, we discuss the opportunities and challenges of studying immune markers in saliva and review the current state of knowledge regarding the study of salivary immune biomeasures, including salivary cytokines, C-reactive protein, and immunoglobulins. Analysis and interpretation issues particularly important for studying immune-related analytes, such as the impact of oral and systemic health, the interpretation of the serum–saliva correlation, and multisystem measurement and analysis techniques, are discussed. Finally, we discuss future directions for the study of salivary immune markers and applications of this research to clinical care and health monitoring and surveillance programs.

The increased risk of Richter transformation (RT) in patients with chronic lymphocytic leukaemia (CLL) due to Epstein-Barr virus (EBV) reactivation during immunosuppressive therapy with fludarabine other targeted agents remains controversial. Among 31 RT cases classified as diffuse large B-cell lymphoma (DLBCL), seven (23%) showed EBV expression. In contrast to EBV- tumours, EBV+ DLBCLs derived predominantly from IGVH-hypermutated CLL, and they also showed CLL-unrelated IGVH sequences more frequently. Intriguingly, despite having different cellular origins, clonally related and unrelated EBV+ DLBCLs shared a previous history of immunosuppressive chemo-immunotherapy, a non-germinal centre DLBCL phenotype, EBV latency programme type II or III, and very short survival. These data suggested that EBV reactivation during therapy-related immunosuppression can transform either CLL cells or non-tumoural B lymphocytes into EBV+ DLBCL. To investigate this hypothesis, xenogeneic transplantation of blood cells from 31 patients with CLL and monoclonal B-cell lymphocytosis (MBL) was performed in Rag2-/- IL2γc-/- mice. Remarkably, the recipients' impaired immunosurveillance favoured the spontaneous outgrowth of EBV+ B-cell clones from 95% of CLL and 64% of MBL patients samples, but not from healthy donors. Eventually, these cells generated monoclonal tumours (mostly CLL-unrelated but also CLL-related), recapitulating the principal features of EBV+ DLBCL in patients. Accordingly, clonally related and unrelated EBV+ DLBCL xenografts showed indistinguishable cellular, virological and molecular features, and synergistically responded to combined inhibition of EBV replication with ganciclovir and B-cell receptor signalling with ibrutinib in vivo. Our study underscores the risk of RT driven by EBV in CLL patients receiving immunosuppressive therapies, and provides the scientific rationale for testing ganciclovir and ibrutinib in EBV+ DLBCL. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Background Inflammation plays a role in mood and behavior that may be relevant to identifying risk factors and treatment for depression and other stress-related illnesses. The purpose of this study was to examine whether fluctuations in inflammation following a mild immune stimulus were associated with changes in daily reported features of depression for up to a week in a healthy sample of young adults. Methods Forty-one undergraduate students completed daily diaries of mood, feelings of social disconnection, sleep, and physical symptoms for one week before and after receiving the seasonal influenza vaccine. Circulating plasma interleukin-6 (IL-6) was measured via blood samples taken immediately before and one day after vaccination. Results There was a significant increase in circulating IL-6 from pre- to post-intervention (p = .008), and there was significant variability in the magnitude of IL-6 change. Greater increases in IL-6 were associated with greater mood disturbance on post-vaccine days, specifically depressed mood and cognitive symptoms. Conclusions Minor increases in inflammation were associated with corresponding increases in features of depression, and these associations occurred in the absence of any physical symptoms. The influenza vaccine could be used to probe causal relationships with a high degree of ecological validity, even in high-risk and vulnerable populations, to better understand the role of inflammation in the pathogenesis of depression.

This study examined the within-and between-person associations between daily negative events - peer problems, academic problems and interparental conflict - and diurnal cortisol in school-age children. Salivary cortisol levels were assessed four times per day (at wakeup, 30min later, just before dinner and at bedtime) on eight days in 47 youths ages 8-13 years old (60% female; M age=11.28, SD=1.50). The relative contributions of within- and between-person variances in each stressor were estimated in models predicting same-day diurnal cortisol slope, same-day bedtime cortisol, and next morning wakeup cortisol. Children who reported more peer problems on average showed flatter slopes of cortisol decline from wakeup to bedtime. However, children secreted more cortisol at wakeup following days when they had reported more peer or academic problems than usual. Interparental conflict was not significantly associated with diurnal cortisol. Findings from this study extend our understanding of short-term cortisol responses to naturally occurring problems in daily life, and help to differentiate these daily processes from the cumulative effects of chronic stress.

A robust body of scientific evidence has indicated that being embedded in high-quality close relationships and feeling socially connected to the people in one's life is associated with decreased risk for all-cause mortality as well as a range of disease morbidities. Despite mounting evidence that the magnitude of these associations is comparable to that of many leading health determinants (that receive significant public health resources), government agencies, health care providers and associations, and public or private health care funders have been slow to recognize human social relationships as either a health determinant or health risk marker in a manner that is comparable to that of other public health priorities. This article evaluates current evidence (on social relationships and health) according to criteria commonly used in determining public health priorities. The article discusses challenges for reducing risk in this area and outlines an agenda for integrating social relationships into current public health priorities. (PsycINFO Database Record

Objective Salivary cortisol is increasingly used as a longitudinal indicator of change in neuroendocrine regulation and as a predictor of health outcomes in youth. The purpose of this study was to describe which indices of HPA-axis functioning are sensitive to changes in parent-child conflict over a three week period and to explore the time course under which these changes can be measured. Methods Youth (n = 47; ages 8–13) completed daily diaries of their conflict with parents for 56 days. On days 17–18 and 38–39, youth contributed saliva samples upon waking, 30-minutes post-waking, afternoon, and bedtime. We assessed change in average diurnal HPA-axis functioning between day 17–18 and day 38–39 as a function of the slopes of change in parent-child conflict over 3 weeks. Results Increasing parent-child conflict was positively associated with concurrent increases in total cortisol output (AUCg), flattening of the diurnal slope, and increases in cortisol at bedtime, but not with change in the cortisol awakening response (CAR). Further, associations between parent-child conflict and both AUCg and bedtime cortisol were observed with at least 14 days of daily diary reporting, whereas any additional ratings of conflict beyond 3 days of daily diaries did not improve model fit for changes in diurnal slope. Conclusions This study demonstrates the within-subject up-regulation of the HPA-axis across three weeks in a healthy sample of youth exposed to natural increases in family conflict. In particular, cortisol at bedtime may be the HPA-axis index that is most sensitive to change over time in parent-child conflict, above and beyond conflict occurring that day. Further, when testing associations between family stressors and diurnal cortisol, the optimal schedule for assessing parent-child conflict varies for different indices of HPA-axis functioning.

Special Issue Guest Editor's Note: In this article the authors discuss potential benefits of normative exposure to stress in children's daily lives, emphasizing development of emotion regulation and coping and functioning of the neuroendocrine and immune systems. In the paired article, "Work-Family Conflict and Health Among Working Parents: Potential Linkages for Family Science and Social Neuroscience" (this issue, pp. 176-190), Grzywacz and Smith examine the stress-based, biobehavioral framework underlying paid work, parenting, and health research and then summarize selected areas of social neuroscience research with a focus on stress and health research as having the potential to further our understanding of how different work-family experiences should be conceived as "stressors" and, if so, how they may get "under the skin" to affect health outcomes.Repeated exposure to chronic stressors like family violence can be detrimental to the mental and physical health of children (Repetti, Taylor, & Seeman, 2002). But these models can be taken too far when extended down in a linear fashion to normative levels of stress exposure. Mild and moderate levels of stress do not necessarily have the same effects on health and development as do high levels of chronic stress, only at a lower level of magnitude. Figure 1 depicts a theoretical inverted U-shaped curve that may better approximate the effects of stress on child development.Thex axisdepictslevelsofexposure,ranging from "very low" to "very high," that reflect a combination of the intensity, frequency, and duration of multiple stressors. Increasing exposure is associated with a decline in functioning only on the right side of the figure, after crossing the midpoint. Most children experience stressors that fall within the broad center of the continuum, where there is a much flatter association with health and development. Although children are potentially exposed to many sources of stress both inside and outside of the home, which can have additive and multiplicative effects, in this article we focus primarily on family stressors. Our goals are to outline potential benefits of exposures to levels of family stress that are in the low to medium range, as well as to review the major biological stress-response systems and the possibilities of showing tolerable responses to high levels of stress.In this article we discuss two, partially overlapping, levels of stress exposure that we have labeled normative and moderate. In our use of the term, a normative level of stress spreads across the low-to-medium range of the x axis in Figure 1. It encompasses daily experiences with common family interactions and events that generate brief, mild expressions of negative affect (e.g., parent-child conflict, family demands, parental disappointment and associated feelings of irritability, frustration, disappointment, and sadness) and occasional events that are more stressful but not outside the ordinary realm of life (e.g., witnessing arguments between parents). We define moderate levels of stress exposure as spanning the medium-to-high sections of the x axis. This is also a very wide range; it includes chronically stressful conditions, such as growing up in neighborhoods with high crime rates, and stressful events, such as parental arguments that recur on a frequent basis, as well as events that are not normative, such as parental divorce. Moderate levels of stress exposure can be associated with poor developmental and health outcomes; our analysis highlights the role of protective factors in these settings.We are concerned with the effects that normative and moderate levels of stress have on the developing child's biological and psychological stress response systems. As we will discuss, normative stressors typically elicit what some have called a "positive" stress response; moderate stressors usually generate more intense emotional and physiological reactions but, under certain supportive conditions, can elicit a "tolerable" stress response (National Scientific Council on the Developing Child, 2005/2014). …

Previous research has linked exposure to adverse social conditions such as chronic stress with DNA damage and accelerated telomere shortening, raising the possibility that psychological stress may impact biological aging pathways, ultimately increasing risk for age-related diseases. Less clear, however, is whether this leads to cell growth arrest and cellular senescence. The present study examined daily diary reports of stress appraisals in 73 parents (Mage = 43.0, SD = 7.2; 55% female) over an 8-week period, along with interview-based and questionnaire (Perceived Stress Scale) measures of adverse exposure to and experience of stress, and markers of cellular aging. Participant blood samples were used to assess two markers of cellular aging: gene expression of senescent cell signal p16INK4a (CDKN2A) and leukocyte telomere length. Random effects models covarying for age, sex, ethnicity, and BMI revealed that participants with greater chronic stress exposure during the 6 months prior to study entry (β = .01, p = .04), higher self-reported perceived stress (β = .02, p < .001), and accumulated daily stress appraisals over the 8-week period (β = .01, p = .01) showed increased gene expression of p16INK4a. No significant associations with telomere length were found. Findings extend previous work on the impact of stress on biological aging by complementing traditional measures of stress exposure with assessments of daily experiences and linking these measures to an accumulation of senescent cells. This study supports the hypothesis that chronic stress is associated with accelerated aging by inducing cellular senescence, a common pathophysiology in age-related diseases.

Interparental conflict is a common source of psychosocial stress in the lives of children. The purpose of this study was to examine the association between recent interparental conflict and one component of the physiological stress response system, the hypothalamic-pituitary-adrenal (HPA)-axis. Parents of 42 children (ages 8-13 years) completed daily diaries of interparental conflict for 8 weeks. At the end of the 8 weeks, youth participated in the Trier Social Stress Test for Children (TSST-C) while providing 2 pre- and 4 poststress salivary cortisol samples. Youth whose fathers reported a pattern of increasing interparental conflict over the past 8 weeks demonstrated an exaggerated HPA-axis response to acute stress. Mother-reported interparental conflict was not associated with children's HPA-axis responses without accounting for fathers' reports. When accounting for fathers' reports, the offspring of mothers reporting higher average daily interparental conflict demonstrated an attenuated HPA-axis response to the stressor. By estimating both average exposure and recent patterns of change in exposure to conflict, we address the circumstances that may prompt attenuation versus sensitization of the HPA-axis in the context of interparental conflict. We conclude that the HPA-axis is sensitive to proximal increases in interparental conflict which may be one pathway through which stress affects health across development, and that incorporating father's reports is important to understanding the role of the family environment in stress responses. This study further demonstrates the value of using intensive repeated measures and multiple reporters to characterize children's psychosocial environment. (PsycINFO Database Record

BACKGROUND: Alterations in reward processing are a central feature of depression and may be influenced by inflammation. Indeed, inflammation is associated with deficits in reward-related processes in animal models and with dysregulation in reward-related neural circuitry in humans. However, the downstream behavioral manifestations of such impairments are rarely examined in humans. METHODS: The influenza vaccination was used to elicit a mild inflammatory response in 41 healthy young adults (age range: 18–22, 30 female). Participants provided blood samples and completed behavioral measures of three key aspects of reward—reward motivation, reward learning, and reward sensitivity—before and 1 day after receiving the influenza vaccine. RESULTS: The influenza vaccine led to mild but significant increases in circulating levels of the pro-inflammatory cytokine interleukin-6 (IL-6) (p < .001). Consistent with hypotheses, increases in IL-6 predicted lower reward motivation (p = .029). However, contrary to hypotheses, increases in IL-6 predicted increased performance on a reward learning task (p = .043) and were not associated with changes in reward sensitivity (p’s > .288). CONCLUSIONS: These findings contribute to an emerging literature on the nuanced associations between inflammation and reward and demonstrate that even mild alterations in inflammation are associated with multiple facets of reward processing.

A wealth of evidence has implicated inflammation in the development of depression. Yet, the heterogeneous nature of depression has impeded efforts to understand, prevent, and treat the disease. The purpose of this integrative review is to summarize the connections between inflammation and established core features of depression that exhibit more homogeneity than the syndrome itself: exaggerated reactivity to negative information, altered reward processing, decreased cognitive control, and somatic syndrome. For each core feature, we first provide a brief overview of its relevance to depression and neurobiological underpinnings, and then review evidence investigating a potential role of inflammation. We focus primarily on findings from experimental paradigms of exogenously-induced inflammation. We conclude that inflammation likely plays a role in exaggerated reactivity to negative information, altered reward reactivity, and somatic symptoms. There is less evidence supporting an effect of inflammation on cognitive control as assessed by standard neuropsychological measures. Finally, we discuss implications for future research and recommendations for how to test the role of inflammation in the pathogenesis of heterogeneous psychiatric disorders.

Friction is a normal part of everyday family life. Parents use conflictual, irritable behavior to communicate that their spouses or children have engaged in unwanted actions. Unfortunately, turbulence in one relationship tends to spread into other relationships, and discord seems to be particularly contagious between the marital and parent-child dyads. The effects of discord in one dyad on the other may amplify the long-term negative outcomes of frequent marital and parent-child conflict that are observed in all members of the family.Marital discord is associated with parents' harshness, inconsistency, psychological control, and reduced acceptance of and sensitivity with their children (Benson, Buehler, & Gerard, 2008; Buehler, Benson, & Gerard, 2006; Klausli & Owen, 2011; for reviews on this topic, see Erel & Burman, 1995; Krishnakumar & Buehler, 2000). In fact, the link between marital discord and parenting may partly explain the association between highly conflictual marriages and child emotional outcomes (Chung, Flook, & Fuligni, 2009; Schulz, Waldinger, Hauser, & Allen, 2005). In the reverse direction, a more limited literature indicates that difficulties between parents and children also affect marital relationships and parents' emotional distress (Almeida, Wethington, & Chandler, 1999; Jenkins, Simpson, Dunn, Rasbash, & O'Connor, 2005; VanderValk, Spruijt, de Goede, & Meeus, 2007).Traditional correlational designs limit the potential for new knowledge about the spread of conflict within families. Although tensions in the marital and parent-child dyads are known to be closely linked, the research literature has less to say about the day-to-day mechanisms by which difficulty in one dyad is transmitted to the other. As a result, researchers have called for process-oriented research to begin to clarify the why and how of established associations between marital and parent-child discord (Cummings & Davies, 2002). Examining daily within-family conflict processes offers an opportunity to take a more detailed look at one potential step along the long pathway from one day's conflictual encounters to long-standing patterns of relational, behavioral, and emotional disturbances in parents and children. Furthermore, assessing short-term within-person processes allows the examination of the day-to-day effects of conflict against the backdrop of the individual's own typical behavior (as opposed to the whole sample's typical behavior), which limits the influence of individual traits, shared genes and environments, and Gene × Environment interactions. This process-level examination offers unique information about daily fluctuations in behavior as compared to the broad associations between marital and parent-child conflict described in cross-sectional and longterm prospective studies.One mechanism by which tension in one family dyad may affect the other dyad on a daily basis is the short-term effects that conflictual encounters have on parents' behavior. Spillover occurs when a stressful experience in one context (e.g., marital conflict) has a direct short-term impact on an individual's affect or behavior in another context (e.g., by increasing the parent's irritability in an interaction with a child; Almeida et al., 1999; Bolger, DeLongis, Kessler, & Wethington, 1989; Repetti, 1987, 1994). A handful of studies have examined short-term effects of marital and parent-child conflict on other family dyads using within-subject methods such as daily diaries (Almeida et al., 1999; Bolger, DeLongis, Kessler, & Wethington, 1989; Chung et al., 2009; Kitzmann, 2000; Margolin, Christensen, & John, 1996). These studies have observed a link from marital conflict to tension in the parent-child relationship on the same or the next day, including both affective (e.g., increases in distressed mood) and behavioral (e.g., disagreements) changes (Almeida et al., 1999; Bolger, DeLongis, Kessler, & Wethington, 1989; Chung et al. …

Despite their functional similarities, peripheral lymphoid tissues are remarkably different according to their developmental properties and structural characteristics, including their specified vasculature. Access of leukocytes to these organs critically depends on their interactions with the local endothelium, where endothelial cells are patterned to display a restricted set of adhesion molecules and other regulatory compounds necessary for extravasation. Recent advances in high throughput analyses of highly purified endothelial subsets in various lymphoid tissues as well as the expansion of various transgenic animal models have shed new light on the transcriptional complexities of lymphoid tissue vascular endothelium. This review is aimed at providing a comprehensive analysis linking the functional competence of spleen and intestinal lymphoid tissues with the developmental programming and functional divergence of their vascular specification, with particular emphasis on the transcriptional control of endothelial cells exerted by Nkx2.3 homeodomain transcription factor.

Older adults make up a larger proportion of the population and are living longer than in any time in previous history, which has important implications for their social relationships. This essay reviews key theory and research on changes in social networks over the lifespan, the benefits (and costs) of social relationships for physical health, and the health impact of loss of social relationships during older age. Methodological innovations are shedding new light on the specific biological mechanisms that explain how high and low quality social relationships can impact health, and we review these innovations in different contexts: marriage and loneliness. While social networks generally decrease in size across the lifespan, there is considerable potential for expanding social networks and forming new relationships in later life. However, the research literature on forming new friendships and intimate relationships in older adults is quite limited. Thus, this essay concludes by describing key issues and methodological challenges involved in studying new relationship formation in older adults. Keywords: social relationships; health; aging; older adults; close relationships; friendship; dating; loneliness; marriage; social support

Regulatory T (Treg) cells can weaken antitumor immune responses, and inhibition of their function appears to be a promising therapeutic approach in cancer patients. Mice with targeted deletion of the gene encoding the Cl-/HCO3- anion exchanger AE2 (also termed SLC4A2), a membrane-bound carrier involved in intracellular pH regulation, showed a progressive decrease in the number of Treg cells. We therefore challenged AE2 as a potential target for tumor therapy, and generated linear peptides designed to bind the third extracellular loop of AE2, which is crucial for its exchange activity. Peptide p17AE2 exhibited optimal interaction ability and indeed promoted apoptosis in mouse and human Treg cells, while activating effector T-cell function. Interestingly, this linear peptide also induced apoptosis in different types of human leukemia, lymphoma and multiple myeloma cell lines and primary malignant samples, while it showed only moderate effects on normal B lymphocytes. Finally, a macrocyclic AE2 targeting peptide exhibiting increased stability in vivo was effective in mice xenografted with B-cell lymphoma. These data suggest that targeting the anion exchanger AE2 with specific peptides may represent an effective therapeutic approach in B-cell malignancies.

To characterise the genetics of splenic marginal zone lymphoma (SMZL), we performed whole exome sequencing of 16 cases and identified novel recurrent inactivating mutations in Kruppel-like factor 2 (KLF2), a gene whose deficiency was previously shown to cause splenic marginal zone hyperplasia in mice. KLF2 mutation was found in 40 (42%) of 96 SMZLs, but rarely in other B-cell lymphomas. The majority of KLF2 mutations were frameshift indels or nonsense changes, with missense mutations clustered in the C-terminal zinc finger domains. Functional assays showed that these mutations inactivated the ability of KLF2 to suppress NF-κB activation by TLR, BCR, BAFFR and TNFR signalling. Further extensive investigations revealed common and distinct genetic changes between SMZL with and without KLF2 mutation. IGHV1-2 rearrangement and 7q deletion were primarily seen in SMZL with KLF2 mutation, while MYD88 and TP53 mutations were nearly exclusively found in those without KLF2 mutation. NOTCH2, TRAF3, TNFAIP3 and CARD11 mutations were observed in SMZL both with and without KLF2 mutation. Taken together, KLF2 mutation is the most common genetic change in SMZL and identifies a subset with a distinct genotype characterised by multi-genetic changes. These different genetic changes may deregulate various signalling pathways and generate cooperative oncogenic properties, thereby contributing to lymphomagenesis.

The effects of kappa opioid receptors (KOR) on motivated behavior are well established based on studies in male rodents, but relatively little is known about the effects of KOR in females. We examined the effects of KOR activation on conditioned place aversion and social interaction in the California mouse (Peromyscus californicus). Important differences were observed in long-term (place aversion) and short-term (social interaction) effects. Females but not males treated with a 2.5. mg/kg dose of U50,488 formed a place aversion, whereas males but not females formed a place aversion at the 10. mg/kg dose. In contrast the short term effects of different doses of U50,488 on social interaction behavior were similar in males and females. Acute injection with 10. mg/kg of U50,488 (but not lower doses) reduced social interaction behavior in both males and females. The effects of U50,488 on phosphorylated extracellular signal regulated kinase (pERK) and p38 MAP kinase were cell type and region specific. Higher doses of U50,488 increased the number of pERK neurons in the ventrolateral bed nucleus of the stria terminals in males but not females, a nucleus implicated in male aggressive behavior. In contrast, both males and females treated with U50,488 had more activated p38 cells in the nucleus accumbens shell. Unexpectedly, cells expressing activated p38 co-expressed Iba-1, a widely used microglia marker. In summary we found strong sex differences in the effects of U50,488 on place aversion whereas the acute effects on U50,488 induced similar behavioral effects in males and females. © 2014 Elsevier B.V.

Increases in inflammation have been linked to meaningful changes in mood and behavior. Individuals exposed to ELS may be particularly vulnerable to the behavioral effects of inflammation. In the present study, participants reported on exposure to early life stress via the Early Trauma Inventory (ETI). Participants then completed a daily mood diary for 14 days. On the 7th day, participants received the flu vaccine. Plasma IL-6 assessed immediately prior to vaccination and 24-h later was used as the measure of inflammatory activation. Individuals in this study (n = 41; Mage = 18.48, SDage = 0.74) were exposed to a wide range of stressful life events during childhood, METI = 4.49, SDETI = 4.02. Exposure to more ELS was not associated with higher baseline IL-6, r=.03, p=.87, or increase in IL-6 following vaccine exposure, r=-.13, p=.40. However, there was a significant interaction between ELS and the magnitude of IL-6 increase, b=.14, SE=.06, p=.029. There was no association between IL-6 response and depressed mood among individuals with 5 or fewer early life events, b=-.49, SE=.69, p=.49, whereas individuals with a score of 6 or more showed greater decrements in mood with a larger IL-6 response, b = 1.68, SE=.53, p=.01. Exposure to ELS may sensitize individuals to the behavioral effects of acute increases in inflammation. Increased vulnerability to the behavioral effects of inflammation may explain the lifelong health disparities associated with childhood adversity.

Previous research has linked exposure to chronic stress with DNA damage and accelerated telomere shortening, raising the possibility that psychosocial stress may impact biological aging pathways, ultimately increasing risk for age-related diseases. Less clear, however, is whether this leads to cell growth arrest and cellular senescence. 73 parents ( M age = 43.0, SD = 7.2; 55% female) completed interview-based and questionnaire (Perceived Stress Scale) measures of their adverse exposure to and experience of stress, as well as daily reports of stress appraisals over an 8-week diary period. Blood samples were used to assess markers of cellular aging: leukocyte telomere length and gene expression of senescent cell signal p16INK4a ( CDKN2A ). Random effects models covarying for age, sex, ethnicity/race, and BMI revealed that participants with greater chronic stress exposure over the previous 6 months ( b = 0.01, p = .04), global perceived stress ( b = 0.02, p .001), and accumulated daily stress appraisals over the 8-week period ( b = 0.01, p = .01) showed increased gene expression of p16INK4a. No significant associations with telomere length were found. Findings extend previous work on the impact of stress on biological aging by linking chronic stress exposure and daily stressful experiences to an accumulation of senescent cells. Findings support the hypothesis that chronic stress is associated with accelerated aging by inducing cellular senescence, a common pathophysiology in age-related diseases.

Attachment theory provides a conceptual framework for understanding intersections between personality and close relationships in adulthood. Moreover, attachment has implications for stress-related physiology and physical health. We review work on normative processes and individual differences in the attachment behavioral system, as well as their associations with biological mechanisms related to health outcomes. We highlight the need for more basic research on normative processes and physiology and discuss our own research on individual differences in attachment and links with physiology. We then describe a novel perspective on attachment and physiology, wherein stress-related physiological changes may also be viewed as supporting the social-cognitive and emotion regulatory functions of the attachment system through providing additional energy to the brain, which has implications for eating behavior and health. We close by discussing our work on individual differences in attachment and restorative processes, including sleep and skin repair, and by stressing the importance of developing biologically plausible models for describing how attachment may impact chronic illness.

SummaryEarlier work demonstrated that the transcription factor C/EBPα can convert immature and mature murine B lineage cells into functional macrophages. Testing >20 human lymphoma and leukemia B cell lines, we found that most can be transdifferentiated at least partially into macrophage-like cells, provided that C/EBPα is expressed at sufficiently high levels. A tamoxifen-inducible subclone of the Seraphina Burkitt lymphoma line, expressing C/EBPαER, could be efficiently converted into phagocytic and quiescent cells with a transcriptome resembling normal macrophages. The converted cells retained their phenotype even when C/EBPα was inactivated, a hallmark of cell reprogramming. Interestingly, C/EBPα induction also impaired the cells’ tumorigenicity. Likewise, C/EBPα efficiently converted a lymphoblastic leukemia B cell line into macrophage-like cells, again dramatically impairing their tumorigenicity. Our experiments show that human cancer cells can be induced by C/EBPα to transdifferentiate into seemingly normal cells at high frequencies and provide a proof of principle for a potential new therapeutic strategy for treating B cell malignancies.

NKX2 homeobox family proteins have a role in cancer development. Here we show that NKX2-3 is overexpressed in tumour cells from a subset of patients with marginal-zone lymphomas, but not with other B-cell malignancies. While Nkx2-3-deficient mice exhibit the absence of marginal-zone B cells, transgenic mice with expression of NKX2-3 in B cells show marginal-zone expansion that leads to the development of tumours, faithfully recapitulating the principal clinical and biological features of human marginal-zone lymphomas. NKX2-3 induces B-cell receptor signalling by phosphorylating Lyn/Syk kinases, which in turn activate multiple integrins (LFA-1, VLA-4), adhesion molecules (ICAM-1, MadCAM-1) and the chemokine receptor CXCR4. These molecules enhance migration, polarization and homing of B cells to splenic and extranodal tissues, eventually driving malignant transformation through triggering NF-κB and PI3K-AKT pathways. This study implicates oncogenic NKX2-3 in lymphomagenesis, and provides a valid experimental mouse model for studying the biology and therapy of human marginal-zone B-cell lymphomas., Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness, FIS-PI12/00202 (to J.A.M.-C.), RTICC-RD12/0036/0063 (to J.A.M-C.), RTICC-RD12/0036/0068 (to M.J.C and F.P.), RTICC-RD12/0036/0022 (to J.L.F-L.), RTICC-RD12/ 0036/0070 (to J.C.), RTICC-RD12/0036/0010 (to B.B.), RTICC- RD12/0036/0044 (to M.J.B.) and RTICC-RD12/0036/0069 (to J.M.H.R. and M.G.); by Worldwide Cancer Research project grant 15-1322 (to J.A.M.-C., Y.R.C. and M.-Q.D.); by BFU2011-30097 (to Y.R.C); by MINECO SAF2013-45787-R and Marie Curie Programme FP7-PIIF-2012-328177 (to S.R.); by the French-Spanish CITTIL project (to F.P., X.A., J.A.M.-C., C.B. and P. Brousset); by SAF2012-32810, SAF2014-57791-REDC; PIE14/00066, BIO/SA32/ 14 and CSI001U14 (to I.S.G); by FIS-ISCIII projects PI13/00160 and PI14/00025, and Fundación Inocente Inocente (to C.C.); by Deutsche Krebshilfe, Molecular Mechanisms in Malignant Lymphomas Network Project (to R.S.); by the Institut Universitaire de France (to P. Brousset); by the Broad Medical Research Program of The Eli and Edythe Broad Foundation and the Hungarian Scientific Research Fund (OTKA K108429) (to P. Balogh)

Dopamine is known to influence motivational processes, however the precise role of this neurotransmitter remains a contentious issue. In the current study we sought to further characterize dopamine signaling in reward-based decision-making and consummatory behavior in mice, via lateral ventricle infusion of the dopamine D2 receptor antagonist eticlopride. In Experiment 1, we examined effort-based decision-making, in which mice had a choice between one lever, where a single response led to the delivery of a low value reward (2% sucrose); and a second lever, which led to a higher value reward (20% sucrose) that gradually required more effort to obtain. As the response schedule for the high value reward became more strict, low dose (4μg in 0.5μl) central infusions of eticlopride biased preference away from the high value reward, and toward the lever that led to the low value reward. Similarly, a higher dose of eticlopride (8μg in 0.5μl) also disrupted choice responding for the high value reward, however it did so by increasing omissions. In Experiment 2, we assessed the effects of eticlopride on consumption of 20% sucrose. The antagonist led to a dose-dependent reduction in intake, and through an analysis of licking microstructure, it was revealed that this in part reflected a reduction in the motivation to engage in consummatory behavior, rather than alterations in the evaluation of the reward. These results suggest that disruptions in D2 receptor signaling reduce the willingness to engage in effortful operant responding and consumption of a desirable outcome.

Norovirus infections are increasingly being recognized as important causes of diarrhea in hematopoietic stem cell transplantation (HSCT) recipients. This retrospective study aimed to evaluate the cumulative incidence, risk factors, and outcomes of norovirus infection in pediatric HSCT recipients. Among 55 patients age

Early life family conflict is associated with physical health problems later in life, but little is known about the biological pathways through which conflict at home exerts it deleterious effects on health. The goal of this study was to investigate the associations between naturalistically assessed conflict in everyday family environments and diurnal cortisol in preschool-aged children.Forty-four children aged 3-5 from two-parent families provided six saliva samples per day over 2 days from a Saturday morning through Sunday night. For a full day on either Saturday or Sunday, children wore a child version of the Electronically Activated Recorder, a digital voice recorder that records ambient sounds while participants go about their daily lives. Parents provided reports of child externalizing behaviors as well as daily reports of child conflicts.Diurnal salivary cortisol over the two weekend days of the study.Greater Electronically Activated Recorder-assessed child conflict at home was associated with children having lower cortisol at wakeup (p.009) and flatter diurnal cortisol slopes (p.007). These associations remained significant even after controlling for parent reports of child externalizing behaviors, parent reports of daily child conflicts, and child age and sex.These findings indicate that taking into consideration everyday conflicts at home may be key to our understanding of stress-health links in young children.

To evaluate the clinical utility of a salivary α-amylase (sAA) biosensor for assessing oral surgery-related stress responses and the differential effect of the personality trait of pain catastrophizing.A prospective cohort study was conducted in 76 healthy subjects who underwent elective removal of their third molars. Along with subjects' self-reports of anxiety and pain, biosensor-facilitated measurements of sAA levels were obtained at multiple time points during the preoperative consult, surgery, and postsurgical follow-up visits. In addition, subjects completed the Pain Catastrophizing Scale at baseline. Mixed-effect regression models examined changes in sAA levels and self-report ratings within and across visits and the contribution of pain catastrophizing.The sAA levels were lower during surgery and postsurgical follow-up compared with the consult visit (P.01). The sAA levels decreased during the surgery visit (P.05) and did not change during the consult or follow-up visits. Individuals who reported greater helplessness to pain manifested higher sAA levels during the surgery visit (P.05). Self-reported anxiety ratings were highest during the surgery visit, and pain ratings were highest during the follow-up visit.The sAA levels did not show the predicted increases during the surgery visit compared with the consult and postsurgical follow-up visits or increases during the surgery visit. However, individuals who reported responding to pain with helplessness had higher sAA levels in anticipation of surgery, providing proof of concept for the value of point-of-care assessments of surgery-induced stresses and the differential effect of personality traits.

The purpose of this study was to present the characteristics and outcome of patients with proven pheochromocytoma or paraganglioma who had false-negative iodine-123 metaiodobenzylguanidine single photon emission computed tomography (123I-MIBG SPECT). Twenty-one patients with false-negative 123I-MIBG SPECT (7 males, 14 females), aged 13–55 years (mean: 41.40 years), were included. We classified them as nonmetastatic or metastatic according to the stage of the disease at the time of false-negative 123I-MIBG SPECT study, the location and size of the tumor, plasma and urinary catecholamine and metanephrine levels, genetic mutations, and outcome in terms of occurrence and progression of metastases and death. Thirteen patients were evaluated for metastatic tumors, while the remaining eight were seen for nonmetastatic disease. All primary tumors and multiple metastatic foci did not show avid 123I-MIBG uptake regardless of the tumor diameter. The majority of patients had extraadrenal tumors with hypersecretion of normetanephrine or norepinephrine. SDHB mutations were present in 52% (n=11) of cases, RET mutation in 4% (n=1), and the rest were apparently sporadic. Twenty-four percent (n=5) had metastatic disease on initial presentation. Fourteen patients were followed for 3–7 years. Of them, 71% (n=10) had metastatic disease and the majority had SDHB mutations. Nine are still alive, while five (four with SDHB) died due to metastatic disease. We concluded that false-negative 123I-MIBG SPECT is frequently related to metastatic tumors and usually due to SDHB mutations with unfavorable prognosis. We therefore recommend that patients with false-negative 123I-MIBG SPECT be tested for SDHB mutations and undergo more regular and close follow-up.

Research on psychological influences on physiology primarily focuses on biological responses during stressful challenges, and how those responses can become dysregulated with prolonged or repeated exposure to stressful circumstances. At the same time, humans spend considerable time recovering from those challenges, and a host of biological processes involved in restoration and repair take place during normal, non-stressed activities. We review restorative biological processes and evidence for links between psychosocial factors and several restorative processes including sleep, wound healing, antioxidant production, DNA repair, and telomerase function. Across these biological processes, a growing body of evidence suggests that experiencing negative emotional states, including acute and chronic stress, depressive symptoms, and individual differences in negative affectivity and hostility, can influence these restorative processes. This review calls attention to restorative processes as fruitful mechanisms and outcomes for future biobehavioral research.

This study examines the effects of actor and partner attachment security on cortisol responses to discussions of personal and relationship concerns with a romantic partner. Dating couples (N = 30) completed two 20-min discussions and provided saliva samples at 4 time points before and after. Hierarchical linear modeling revealed that among women, higher levels of partner avoidance predicted greater cortisol reactivity to both discussions and among men, higher levels of actor anxiety predicted greater reactivity to the relationship concern discussion. These findings extend previous work by demonstrating that the effects of attachment on physiology vary by gender and by discussion context, which informs our understanding of how individual differences in attachment moderate the effects of romantic relationships on health. The quality of close relationships has a powerful influence on physical health. Individuals in less distressed, higher quality marriages are in better health (Burman & Maroglin, 1992) and experience smaller declines in health as they age (Umberson, Williams, Powers, Liu, & Needham, 2006) than individuals in low-quality marriages. One pathway by which relationship quality may ultimately affect health involves activity in the hypothalamic–pituitary–adrenal (HPA) axis and production of the hormone cortisol. Short-term

BACKGROUND To estimate the incidence of aneuploidy in relation to patients' characteristics, the type of hormonal stimulation and their response to induction of multiple follicular growth, 4163 first polar bodies (PB1s) were analyzed. METHODS Five hundred and forty four infertile couples underwent 706 assisted conception cycles (640 with poor prognosis indications and 66 controls) in which chromosomal analysis of PB1 for the chromosomes 13, 15, 16, 18, 21 and 22 was performed. Results were evaluated in a multivariate analysis. RESULTS The proportion of normal oocytes was directly correlated (P < 0.01) with (i) the number of mature oocytes and (ii) the establishment of a clinical pregnancy; and inversely correlated (P < 0.01) with (i) female age, (ii) causes of female infertility (endometriosis, abortions, ovulatory factor), (iii) poor prognosis indications (female age, number of previous cycles, multiple poor prognosis indications), (iv) number of FSH units per oocyte and (v) number of FSH units per metaphase II oocyte. There was a weak significance of frequency (P < 0.05) between type of abnormality (originated by chromatid predivision, chromosome non-disjunction or combined mechanisms in the same oocyte) and groups of the studied variables, rather than to a specific abnormality or a specific chromosome. CONCLUSIONS The type of infertility had a significant effect on errors derived from the first meiotic division, whose incidence was significantly higher in the presence of endometriosis or of an ovulatory factor, and in women that experienced repeated abortions. Each aneuploidy event was found to be dependent not on a specific variable, but on groups of variables. In addition, the tendency of chromosomal abnormalities to occur simultaneously implies that the deriving aneuploidies can be of any type.

This journal suppl. entitled: Abstracts of the 26th Annual Meeting of the European Society of Human Reproduction and Embryology, Rome, Italy, 27-30 June 2010

Behavioral scientists have increasingly included inflammatory biology as mechanisms in their investigation of psychosocial dynamics on the pathobiology of disease. However, a lack of standardization of inclusion and exclusion criteria and assessment of relevant control variables impacts the interpretation of these studies. The present paper reviews and discusses human biobehavioral factors that can affect the measurement of circulating markers of inflammation. Keywords relevant to inflammatory biology and biobehavioral factors were searched through PubMed. Age, sex, and hormonal status, socioeconomic status, ethnicity and race, body mass index, exercise, diet, caffeine, smoking, alcohol, sleep disruption, antidepressants, aspirin, and medications for cardiovascular disease are all reviewed. A tiered set of recommendations as to whether each variable should be assessed, controlled for, or used as an exclusion criteria is provided. These recommendations provide a framework for observational and intervention studies investigating linkages between psychosocial and behavioral factors and inflammation.

The experience of positive affect (PA) is related to a variety of health benefits such as increased longevity, decreased morbidity, and less experience of pain (reviewed in Pressman & Cohen, 2005). Several prospective studies show that PA predicts decreased morbidity, such as lower incidence of stroke in older adults (Ostir, Markides, Peek, & Goodwin, 2001), and lower incidence of developing symptoms of the common cold after inoculation with cold virus (Cohen, Doyle, Turner, Alper, & Skoner, 2003). iThese studies importantly demonstrated that the effects of PA are independent of disease processes, as participants were healthy at baseline, and that dispositional or trait PA showed effects on morbidity independent of the effects of negative affect. Moreover, prospective effects of trait PA were observed in a range of health outcomes (e.g., pregnancy outcomes, injury, stroke, and hospital readmission). The specific mechanisms through which trait PA influences health operate through two general frameworks proposed by Pressman and Cohen (2005). One proposed framework is a direct effects model, in which trait PA impacts behaviors and biological systems relevant for health in general, irrespective of its effects on responses to stress. For example, individuals with high trait PA may be more likely to engage in health-promoting behaviors or have lower tonic levels of catecholamines or glucocorticoid hormones. By contrast, in a stress-buffering model, dispositional levels of PA may “buffer” against the harmful biological and health consequences of exposure to stressors. Individuals with high trait PA may be able to cope more effectively with stressful events and consequently, may not experience the negative health consequences of psychological stress. This stress-buffering hypothesis is consistent with Fredrickson’s “Broaden and Build” theory of positive emotions (Fredrickson, 1998), in which positive emotions result in the building of social, intellectual, and physical resources by broadening action tendencies and generating psychological resources (Salovey, Rothman, Detweiler, & Steward, 2000). Thus, social and psychological resources available to individuals high in trait PA may be drawn upon when challenged with stressful events. Regardless of whether PA influences health through direct effects or by buffering stress, there is some evidence for specific biological mechanisms that may tie PA to health, including neuroendocrine and immune function (Cohen et al., 2003; Marsland, Cohen, Rabin, & Manuck, 2006; Steptoe, Wardle, & Marmot, 2005). An additional biological mechanism that may explain links between trait PA and health is processes involved in skin repair and wound healing, which are clinically relevant and can be measured in a brief period of time in healthy individuals. The skin is the largest organ of the body. The outermost layer of the skin, the stratum corneum, has a number of protective “barrier” functions, including defending against microbes; keeping the skin cohesive and intact despite physical damage; protecting the interior against chemical absorption, ultraviolet rays, and extreme temperature; and preventing water loss (Elias, 2005). If the skin barrier is compromised by wounding, all the previously described functions are impaired, which further impair recovery from skin damage, protection against future damage, and susceptibility to infectious illness. Much like inflammatory processes, which have multiple effects on the organism and are of considerable interest to health psychologists (Kiecolt-Glaser, McGuire, Robles, & Glaser, 2002), problems with skin repair and wound healing extend to other important biological activities that protect and preserve our health. More generally, wound healing provides a model system for understanding the impact of psychological factors on health within a short period of time. Exposure to acute and chronic stress is related to delayed healing of full-thickness wounds (e.g., punch biopsy) that penetrate both the epidermis and underlying dermis (reviewed in Christian, Graham, Padgett, Glaser, & Kiecolt-Glaser, 2006). Psychological stress may also disrupt the skin’s ability to recover its function as a barrier against moisture loss and pathogens after more minor disruption, such as damage to the stratum corneum. Across several studies, skin barrier recovery was reduced by 10%–15% following a brief laboratory stressor (Altemus, Rao, Dhabhar, Ding, & Granstein, 2001; Robles, 2007). Approximately 30% recovery was achieved at 3 h after skin disruption during medical school examinations, compared to 45% recovery during the end of winter and spring vacation (Garg et al., 2001). These studies suggest that skin barrier recovery may be a useful model for examining the impact of psychosocial factors such as psychological stress on health and suggest a pathway through which trait PA may impact health. However, few studies published to date have explored the role of individual difference characteristics, such as trait PA, on wound healing in response to stress. This study tested whether individual differences in trait PA are related to skin barrier recovery, and whether the role of trait PA in wound healing is consistent with the direct effects model or the stress-buffering model. In this study, we assessed trait levels of PA and negative affect (NA) in participants, who were then randomly assigned to go through a brief psychological stressor or no stressor. The direct effects model predicts that individuals with greater trait PA will show faster skin barrier recovery, regardless of the presence of psychological stress, while the stress-buffering model predicts that greater trait PA will be related to faster skin barrier recovery in individuals undergoing a stressor. Based on previous work on the effects of PA on reducing the negative psychological and biological impact of psychological stress (Steptoe et al., 2005; Tugade & Fredrickson, 2004) and the effects of psychological stress on skin barrier recovery (Altemus et al., 2001; Garg et al., 2001), we predicted that greater trait PA would be related to faster skin barrier recovery following exposure to a laboratory stressor, consistent with the stress-buffering model.

Resumen Objetivos Adaptar al espanol la terminologia del tracto urinario inferior en el ambito pediatrico con motivo del informe de la ICCS de 2006 Material y metodologia se han mantenido discusiones en la Reunion de Consenso en conceptos y terminologia en la que han participado miembros de Grupos Espanol de Urodinamica y de la Sociedad Iberoamericana de Neurourologia y Uroginecologia (SINUG) Resultados y conclusiones Se ofrecen las nuevas definiciones y terminologia estandarizada en espanol, que tiene en cuenta los cambios realizados en el ambito de los adultos y los nuevos resultados en la investigacion. Se presentan los terminos ingleses (frecuentemente entre parentesis). Se discuten algunas propuestas (usualmente en las notas al pie)

The majority of adults sleep with a partner, and for a significant proportion of couples, sleep problems and relationship problems co-occur, yet there has been little systematic study of the association between close relationships and sleep. The association between sleep and relationships is likely to be bi-directional and reciprocal—the quality of close relationships influences sleep and sleep disturbances or sleep disorders influence close relationship quality. Therefore, the purpose of the present review is to summarize the extant research on 1) the impact of co-sleeping on bed partner's sleep; 2) the impact of sleep disturbance or sleep disorders on relationship functioning; and 3) the impact of close personal relationship quality on sleep. In addition, we provide a conceptual model of biopsychosocial pathways to account for the covariation between relationship functioning and sleep. Recognizing the dyadic nature of sleep and incorporating such knowledge into both clinical practice and research in sleep medicine may elucidate key mechanisms in the etiology and maintenance of both sleep disorders and relationship problems and may ultimately inform novel treatments.

Splenic marginal zone lymphoma is a rare lymphoma. Loss of 7q31 and somatic mutations affecting the NOTCH2 and KLF2 genes are the commonest genomic aberrations. Epigenetic changes can be pharmacologically reverted; therefore, identification of groups of patients with specific epigenomic alterations might have therapeutic relevance. Here we integrated genome-wide DNA-promoter methylation profiling with gene expression profiling, and clinical and biological variables. An unsupervised clustering analysis of a test series of 98 samples identified 2 clusters with different degrees of promoter methylation. The cluster comprising samples with higher-promoter methylation (High-M) had a poorer overall survival compared with the lower (Low-M) cluster. The prognostic relevance of the High-M phenotype was confirmed in an independent validation set of 36 patients. In the whole series, the High-M phenotype was associated with IGHV1-02 usage, mutations of NOTCH2 gene, 7q31-32 loss, and histologic transformation. In the High-M set, a number of tumor-suppressor genes were methylated and repressed. PRC2 subunit genes and several prosurvival lymphoma genes were unmethylated and overexpressed. A model based on the methylation of 3 genes (CACNB2, HTRA1, KLF4) identified a poorer-outcome patient subset. Exposure of splenic marginal zone lymphoma cell lines to a demethylating agent caused partial reversion of the High-M phenotype and inhibition of proliferation.

Chronically elevated systemic inflammation has a dramatic impact on health for older individuals. As stress-related responses, both hostility and pain perception may contribute to inflammation which in turn may maintain negative emotion and pain over time. We used structural equation modeling to examine the degree to which trait hostility and pain were uniquely associated with C-reactive protein (CRP) and serum IL-6 levels over a 6-year span in a sample of older adults. The sample included 113 present or former caregivers of a spouse with dementia and 101 non-caregivers. After accounting for depression, health behaviours, and other risk factors, which were also assessed longitudinally, pain and, to a lesser extent, hostility were uniquely associated with plasma levels of CRP but not IL-6. When examined separately, the association between pain and CRP was significant only for caregivers, while the association between hostility and CRP was comparable for the two groups. These findings suggest that hostility may play a role in a cycle of inflammation among older adults, and that pain may be particularly problematic for those under chronic stress. Our results also shed light on inflammation as a mechanism underlying the effects of hostility on cardiovascular disease morbidity and mortality.

To examine the independent and interactive contribution of positive and negative behaviors during marital conflict to changes in adrenocorticotropic hormone (ACTH) and cortisol, behavioral and endocrine data were collected from 90 newlywed couples during a 30-minute conflict task. Positive and negative behaviors were coded by the Marital Interaction Coding System. High levels of husbands' positive behavior and high couple negativity were related to steeper ACTH and cortisol declines in wives. Low levels of wives' positive behavior and high couple negativity were related to flatter declines in wives' cortisol. Supportiveness during highly negative interactions contributed to steeper ACTH and cortisol declines in wives, suggesting that constructively engaging in discussions promotes adaptive physiological responses to interpersonal conflict.

Background: Health system delay (HSD) is an important issue in tuberculosis (TB) control. This report investigates HSD and associated factors in a cohort of Spanish culture-confirmed TB patients. Methods: Data were collected from clinical records. Using logistic regression with two different cut-off points to define HSD (median and 75th percentile), adjusted odds ratios were used to estimate the association between HSD and different variables. Results: A total of 5184 culture-confirmed TB cases were included. Median and 75th percentile HSD were 6 and 25 days respectively. HSD significantly greater than the median was associated with: age >44 years, past or present intravenous drug use, diagnosis at a primary-care centre, prior preventive therapy, positive histology, request for drug-sensitivity testing, presence of silicosis or neoplasia in addition to TB, presence of non-TB related symptoms, and gastrointestinal site. HSD greater than the 75th percentile was related to the same variables, with the exception of diagnosis at a primary-care centre, positive histology, silicosis, non-TB-related symptoms and gastrointestinal site, for which the association disappeared; in contrast, an association with female gender emerged. Conclusion: Despite free health care being universally available in Spain, there are some groups of TB patients whose treatment is unduly delayed.