Sex Differences in the Effect of Inflammation on Subjective Social Status: A Randomized Controlled Trial of Endotoxin in Healthy Young Adults.

It has been established that inflammation leads to a variety of changes in social experience, but one area of social experience that has been overlooked is subjective social status. Furthermore, given sex differences in the relationship between inflammation and social status, males may be more sensitive to inflammation-induced changes in social status. However, no previous studies in humans have examined this possibility. In the present study, healthy young participants (n = 115) were randomly assigned to receive either endotoxin, an experimental inflammatory challenge, or placebo. Participants reported their subjective social status at baseline (prior to injection), and approximately 2 h later (time of peak inflammatory response for the endotoxin group). Results, using ANCOVA analyses, indicated that males exposed to endotoxin, but not females, reported lower levels of subjective social status at the peak of inflammatory response (vs. placebo). These results suggest that males may be more sensitive to the effects of inflammation in certain social domains, such as perceived social status. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01671150

Goal-Focused Emotion-Regulation Therapy (GET) for young adult survivors of testicular cancer: a pilot randomized controlled trial of a biobehavioral intervention protocol.

BackgroundTesticular cancer diagnosis and treatment, especially given its threat to sexuality and reproductive health, can be distressing in the formative period of young adulthood and the majority of young survivors experience impairing, distressing, and modifiable adverse outcomes that can persist long after medical treatment. These include psychological distress, impairment in pursuit of life goals, persistent physical side effects, elevated risk of secondary malignancies and chronic illness, and biobehavioral burden (e.g., enhanced inflammation, dysregulated diurnal stress hormones). However, few targeted interventions exist to assist young survivors in renegotiating life goals and regulating cancer-related emotions, and none focus on reducing the burden of morbidity via biobehavioral mechanisms. This paper describes the methodology of a randomized controlled biobehavioral trial designed to investigate the feasibility and preliminary impact of a novel intervention, Goal-focused Emotion-Regulation Therapy (GET), aimed at improving distress symptoms, emotion regulation, goal navigation skills, and stress-sensitive biomarkers in young adult testicular cancer patients.MethodsParticipants will be randomized to receive six sessions of GET or Individual Supportive Therapy (ISP) delivered over 8 weeks. In addition to indicators of intervention feasibility, we will measure primary (depressive and anxiety symptoms) and secondary (emotion regulation and goal navigation skills, career confusion) psychological outcomes prior to (T0), immediately after (T1), and 12 weeks after (T2) intervention. Additionally, identified biomarkers will be measured at baseline and at T2.DiscussionGET may have the potential to improve self-regulation across biobehavioral domains, improve overall cancer adjustment, and address the need for targeted supportive care interventions for young adult cancer survivors.Trial registrationClinicaltrials.gov, NCT04150848. Registered on 28 October 2019

Increased risk of depression in non-depressed HIV infected men with sleep disturbance: Prospective findings from the Multicenter AIDS Cohort Study.

ObjectiveSleep disturbance is a known risk factor for depression, but it is not known whether sleep disturbance contributes to greater risk of depression in those infected with human immunodeficiency virus (HIV+) as compared to those uninfected with HIV (HIV-).MethodsUsing data from the Multicenter AIDS Cohort Study, a population-based prospective study of men who have sex with men (MSM), self-reported sleep disturbance (>2 weeks) and depressive symptoms (Clinical Epidemiologic Scale for Depression, CES-D) were assessed every 6 months over 12 years of follow-up. Adjusted mixed effects logistic regression analyses tested whether sleep disturbance predicted depression (CES-D ≥ 16) at the immediate subsequent visit, and so on over 12 years, in non-depressed HIV+(N = 1054; 9556 person-visits) and non-depressed HIV- (N = 1217; 12,680 person-visits). In HIV+ vs. HIV- MSM, linearly estimated average incidence of depression and normalized cumulative rate of depression over 12 years were compared.ResultsIn the HIV+ MSM, sleep disturbance was associated with a significant increase in depression 6 months later (OR = 1.6; 95% CI, 1.30, 1.96), which was significantly greater (P < .05) than in HIV- MSM (OR = 1.16; 95% CI, 0.94, 1.44). HIV status and sleep disturbance interacted (P < .001), such that incidence of depression and normalized cumulative rate of depression were greater in HIV+ with sleep disturbance than in HIV+ without sleep disturbance and HIV- groups (all P's < 0.001).ConclusionsHIV+ persons who report sleep disturbance represent a high risk group to be monitored for depression, and possibly targeted for insomnia treatment to prevent depression. FUND: National Institute of Allergy and Infectious Diseases

Sex differences in the transcriptional response to acute inflammatory challenge: A randomized controlled trial of endotoxin

Background: Sex differences in immune-based disorders are well-established, with female sex associated with a markedly heightened risk of autoimmune disease. Female sex is also overrepresented in other conditions associated with elevated inflammation, including depression, chronic pain, and chronic fatigue. The mechanisms underlying these disparities are unclear. This study used an experimental model of inflammatory challenge to interrogate molecular mechanisms that may contribute to female vulnerability to disorders with an inflammatory basis. Method: In this analysis of a secondary outcome from a randomized controlled trial, 111 participants (67 female) received either a bolus injection of endotoxin (n = 59) or placebo (n = 52). Participants provided blood samples before and 0.5 h post-injection for assessment of differential activation of key pro-inflammatory (i.e., activator protein (AP)-1; nuclear factor (NF)-κB) and immunoregulatory (i.e., glucocorticoid receptor (GR); cAMP response element binding protein (CREB)) signaling pathways via genome-wide expression profiling and promoter-based bioinformatics analyses. Results: Relative to males, females exhibited greater endotoxin-induced increases in bioinformatic measures of CREB transcription factor activity (p's < 0.01). However, contrary to hypotheses, female vs. male sex was not associated with greater increases in activation of NF-κB, AP-1, or GR in response to endotoxin vs. placebo administration. Conclusions: This work suggests CREB signaling as a critical upstream biological pathway that should be further interrogated as a mechanism of female vulnerability to immune-related disorders. Future work should clarify whether increased CREB signaling indicates sex differences in activity of the sympathetic nervous system or other physiological pathways that signal through CREB, such as prostaglandin release

Biomarkers of aging associated with past treatments in breast cancer survivors.

Radiation and chemotherapy are effective treatments for cancer, but are also toxic to healthy cells. Little is known about whether prior exposure to these treatments is related to markers of cellular aging years later in breast cancer survivors. We examined whether past exposure to chemotherapy and/or radiation treatment was associated with DNA damage, telomerase activity, and telomere length 3-6 years after completion of primary treatments in breast cancer survivors (stage 0-IIIA breast cancer at diagnosis). We also examined the relationship of these cellular aging markers with plasma levels of Interleukin (IL)-6, soluble TNF-receptor-II (sTNF-RII), and C-reactive protein (CRP). Ninety-four women (36.4-69.5 years; 80% white) were evaluated. Analyses adjusting for age, race, BMI, and years from last treatment found that women who had prior exposure to chemotherapy and/or radiation compared to women who had previously received surgery alone were more likely to have higher levels of DNA damage (P = .02) and lower telomerase activity (P = .02), but did not have differences in telomere length. More DNA damage and lower telomerase were each associated with higher levels of sTNF-RII (P's < .05). We found that exposure to chemotherapy and/or radiation 3-6 years prior was associated with markers of cellular aging, including higher DNA damage and lower telomerase activity, in post-treatment breast cancer survivors. Furthermore, these measures were associated with elevated inflammatory activation, as indexed by sTNF-RII. Given that these differences were observed many years after the treatment, the findings suggest a long lasting effect of chemotherapy and/or radiation exposure

Vacuum polarization on the brane

We compute the renormalized expectation value of the square of a massless, conformally coupled, quantum scalar field on the brane of a higher-dimensional black hole. Working in the AADD brane-world scenario, the extra dimensions are flat and we assume that the compactification radius is large compared with the size of the black hole. The four-dimensional on-brane metric corresponds to a slice through a higher-dimensional Schwarzschild-Tangherlini black hole geometry and depends on the number of bulk space-time dimensions. The quantum scalar field is in a thermal state at the Hawking temperature. An exact, closed-form expression is derived for the renormalized expectation value of the square of the quantum scalar field on the event horizon of the black hole. Outside the event horizon, this renormalized expectation value is computed numerically. The answer depends on the number of bulk space-time dimensions, with a magnitude which increases rapidly as the number of bulk space-time dimensions increases

Self-reported sleep duration mitigates the association between inflammation and cognitive functioning in hospitalized older men

Examination of predictors of late-life cognitive functioning is particularly salient in at-risk older adults, such as those who have been recently hospitalized. Sleep and inflammation are independently related to late-life cognitive functioning. The potential role of sleep as a moderator of the relationship between inflammation and global cognitive functioning has not been adequately addressed. We examined the relationship between self-reported sleep duration, inflammatory markers, and general cognitive functioning in hospitalized older men. Older men (n = 135; Mean age = 72.9 ± 9.7 years) were recruited from inpatient rehabilitation units at a VA Medical Center to participate in a cross-sectional study of sleep. Participants completed the Mini-Mental State Examination and Pittsburgh Sleep Quality Index, and underwent an 8 a.m. blood draw to measure inflammatory markers [i.e., C-reactive protein (CRP), tumor necrosis factor alpha (TNFα), soluble intercellular adhesion molecule-1 (sICAM-1), and interleukin-6 (IL-6)]. Hierarchical regression analyses (controlling for age, education, race, depression, pain, health comorbidity, and BMI) revealed that higher levels of CRP and sICAM are associated with higher global cognitive functioning in older men with sleep duration ≥6 h (β = -0.19, β = -0.18, p's < 0.05, respectively), but not in those with short sleep durations (p's > 0.05). In elderly hospitalized men, sleep duration moderates the association between inflammation and cognitive functioning. These findings have implications for the clinical care of older men within medical settings