Diminished Cellular Immunity and Executive Cognitive Functioning Among Middle-Aged and Elderly Adults.

OBJECTIVE: Within the field of psychoneuroimmunology, much attention has been given to immune dysregulation and its impact on cognitive functioning. Some of this work has focused on the association between high levels of basal proinflammatory cytokines and poorer performance on measures of executive functioning; however, effect sizes have been quite small in human studies. METHODS: We investigated whether Epstein-Barr virus (EBV) antibody titers, a marker of immune dysregulation related to cellular immunity, may be associated with executive functioning while also attempting to replicate prior studies using two markers of proinflammatory cytokine production (i.e., circulating and lipopolysaccharide [LPS]-stimulated cytokines [interleukin 6, interleukin 1ß, interferon-γ]). A total of 71 community-dwelling adults (mean [standard deviation] age = 60.87 [6.26] years) who were seropositive for EBV infection participated in the study. RESULTS: Findings indicated that greater EBV antibody titers were associated with poorer performance on measures of the executive functions of inhibition ( B = -2.36, standard error = 1.06, p = .028) and cognitive flexibility ( B = -2.89, standard error = 1.13, p = .013) when including circulating and LPS-stimulated cytokines and other relevant covariates (i.e., age, sex, and body mass index) in linear regression analyses. Neither circulating nor LPS-stimulated cytokines were associated with performance on the cognitive tasks in the regression analyses. CONCLUSIONS: These results suggest that EBV antibody titers may be an indicator of immune dysregulation that is more relevant to executive functioning performance than either circulating or stimulated proinflammatory cytokines among community-dwelling adults.

The mastery lifestyle intervention to reduce biopsychosocial risks for pregnant Latinas and African Americans and their infants: protocol for a randomized controlled trial.

BACKGROUND: Pregnant Mexican Americans (hereafter called Latinas) and Black/African American women are at increased risk for psychological distress, contributing to preterm birth and low birthweight; acculturative stress combined with perceived stress elevates depressive symptoms in Latinas. Based on our prior research using a psychoneuroimmunology framework, we identified psychological and neuroendocrine risk factors as predictors of preterm birth in Latina women that are also identified as risk factors for Black/African American women. METHODS/DESIGN: In this prospective, randomized controlled trial with parallel group design we will explore psychosocial, neuroendocrine, and birth outcome effects of the Mastery Lifestyle Intervention (MLI). The MLI is a culturally relevant, manualized, psychosocial, group intervention integrating two cognitive behavioral therapies for both pregnant Latinas and Black/African American women (total n = 221). Study inclusion criteria are: women with current pregnancy at 14-20 weeks gestation, ability to read and speak English or Spanish, self-identify as Latina of Mexican heritage or Black/African American, 18-45 years old, born in the US or Mexico, and currently living in the US. Participants must receive Medicaid or other government-supported insurance, and meet screening criteria for anxiety, depressive symptoms, or stress. Participants are randomly assigned to either the intervention (MLI) or usual care group (UCG) in groups of 6-8 participants that occur over 6 consecutive weeks. Data are collected at 3 time points: enrollment (14-20 weeks gestation), following treatment (20-26 weeks), and 6 weeks after treatment (32-36 weeks gestation). Additional outcome, mediating, and moderating data are collected from the electronic health record during pregnancy and at birth. Analyses will primarily use generalized linear mixed modeling (GLMM) to evaluate the relationships between predictors and outcomes. DISCUSSION: This RCT will test the efficacy of two combined third generation cognitive behavioral therapies (the MLI), given in a group format over 6 sessions, as compared to a usual prenatal care group, for both Latina and African American pregnant women. If efficacious, it may be provided as an adjunct to routine prenatal care and improve mental health, as well as babies being born too small and too soon. TRIAL REGISTRATION: The trial was retrospectively registered at ClinicalTrials.gov . Bethesda (MD): National Library of Medicine. Identifier NCT05012072 , Reducing Pregnancy Risks: The Mastery Lifestyle Intervention (MLI); August 19, 2021. The trial is currently recruiting participants.

Perceived Social Support and Latent Herpesvirus Reactivation: Testing Main and Stress-Buffering Effects in an Ethnically Diverse Sample of Adults.

OBJECTIVE: Perceived social support is consistently associated with physical health outcomes, and one potential physiological mechanism underlying this association is immune function. In this study, we tested both the main and stress-buffering effects of perceived social support on cellular immunity measured via latent herpesvirus reactivation. METHODS: Data were collected from a community-based sample of 1443 ethnically diverse adults between the ages of 25 and 90 years. Participants self-reported measures of perceived social support, stressful life events, daily hassles, and perceived stress, and provided a blood sample to assess antibody titers to the herpes simplex virus type 1 and Epstein-Barr virus (EBV). RESULTS: In accordance with the main effect hypothesis, results indicated that perceived social support was directly associated with EBV viral capsid antigen antibody titers (ß = -0.06, 95% confidence interval = -0.12 to -0.01, p = .029). Perceived social support, however, did not interact with stressful life events, daily hassles, or perceived stress to influence latent herpesvirus reactivation (p values > .05). Neither race/ethnicity nor age moderated any of the interactions between perceived social support and the stress measures on latent herpesvirus reactivation (p values > .10). CONCLUSIONS: Overall, the current study supports the main effect hypothesis, according to which higher levels of perceived social support were associated with lower levels of herpesvirus antibody titers.

Immune sensitization during 1 year in the Antarctic high-altitude Concordia Environment.

BACKGROUND: Antarctica is a challenging environment for humans. It serves as a spaceflight ground analog, reflecting some conditions of long-duration exploration class space missions. The French-Italian Concordia station in interior Antarctica is a high-fidelity analog, located 1000 km from the coast, at an altitude of 3232 m. The aim of this field study was to characterize the extent, dynamics, and key mechanisms of the immune adaptation in humans overwintering at Concordia for 1 year. METHODS: This study assessed immune functions in fourteen crewmembers. Quantitative and phenotypic analyses from human blood were performed using onsite flow cytometry together with specific tests on receptor-dependent and receptor-independent functional innate and adaptive immune responses. Transcriptome analyses and quantitative identification of key response genes were assessed. RESULTS: Dynamic immune activation and a two-step escalation/activation pattern were observed. The early phase was characterized by moderately sensitized global immune responses, while after 3-4 months, immune responses were highly upregulated. The cytokine responses to an ex vivo stimulation were markedly raised above baseline levels. These functional observations were reflected at the gene transcriptional level in particular through the modulation of hypoxia-driven pathways. CONCLUSIONS: This study revealed unique insights into the extent, dynamics, and genetics of immune dysfunctions in humans exposed for 1 year to the Antarctic environment at the Concordia station. The scale of immune function was imbalanced toward a sensitizing of inflammatory pathways.

Psychological and Biological Pathways Linking Perceived Neighborhood Characteristics and Body Mass Index.

BACKGROUND: Perceived neighborhood characteristics are linked to obesity, however, the mechanisms linking these two factors remain unknown. PURPOSE: This study aimed to examine associations between perceived neighborhood characteristics and body mass index (BMI), establish whether indirect pathways through psychological distress and inflammation are important, and determine whether these associations vary by race/ethnicity. METHODS: Participants were 1,112 adults enrolled in the Texas City Stress and Health Study. Perceived neighborhood characteristics were measured using the Perceived Neighborhood Scale. Psychological distress was measured with the Center for Epidemiological Studies Depression Scale, Perceived Stress Scale and mental health subscale of the Short Form Health Survey-36. Markers of inflammation included C-reactive protein, interleukin-6, and tumor necrosis factor receptor-1. Associations were examined with Structural Equation Modeling. RESULTS: A model linking neighborhood characteristics with BMI through direct and indirect (i.e., psychological distress and inflammation) paths demonstrated good fit with the data. Less favorable perceived neighborhood characteristics were associated with greater psychological distress (B = -0.87, ß = -0.31, p < .001) and inflammation (B = -0.02, ß = -0.10, p = .035). Psychological distress and inflammation were also significantly associated with BMI (Bdistress = 0.06, ß = 0.08, p = .006; Binflammation = 4.65, ß = 0.41, p < .001). Indirect paths from neighborhood characteristics to BMI via psychological distress (B = -0.05, ß = -0.03, p = .004) and inflammation (B = -0.08, ß = -0.04, p = .045) were significant. In multiple group analysis, a model with parameters constrained equal across race/ethnicity showed adequate fit suggesting associations were comparable across groups. CONCLUSION: Our study extends the literature by demonstrating the importance of neighborhood perceptions as correlates of BMI across race/ethnicity, and highlights the role of psychological and physiological pathways.

Pilot Study of the Mastery Lifestyle Intervention.

BACKGROUND: Recognizing the effects of acculturation on quality of life and emotional health, especially during pregnancy, we developed an intervention that would target these factors in order to improve maternal well-being during the prenatal period and potentially improve infant outcomes, particularly preterm birth for Mexican-American women (Latinas). OBJECTIVE: The purpose of these pilot studies was to test the acceptability, feasibility, and preliminary efficacy of the mastery lifestyle intervention (MLI) to decrease depressive and anxiety symptoms and improve coping as implemented in prenatal clinics with culturally homogenous groups of Latinas. METHODS: The MLI was tested in three small pilot studies (n = 15), one in El Paso, Texas (an urban area), and two in Bastrop, Texas (a rural area outside Austin), for acceptability and feasibility. A pretest/posttest, quasi-experimental design was used with pregnant self-identified Mexican-American Latinas at 14-20 weeks' gestation. Measures of anxiety, depressive symptoms, and positive and negative coping were used. RESULTS: Feasibility was a success in terms of implementation of the MLI in an active prenatal clinic setting and the use of electronic tablets for data collection and entry of data into REDcap. Satisfaction was high, with the location of the MLI being at their primary OB/GYN clinic. Participants reported that six intervention sessions appear to be ideal as was the class length of 1.5 to 2 hours. On Cohen's d, there were medium to large effect size decreases in depressive and anxiety symptoms and small to medium effect size decreases in the use of negative coping strategies and small effect sizes for increases in positive coping strategies. DISCUSSION: Pilot testing of the MLI indicated that it was well accepted from the participants and feasible as a culturally tailored behavioral therapy administered in a group setting by nurse practitioners. Our initial pilot results also suggest preliminary efficacy as indicated by moderate to large Cohen's d effect sizes for depression and anxiety.

An Evaluation of Perceived Health Risk and Depressive Symptoms Before a Disaster in Predicting Postdisaster Inflammation.

OBJECTIVE: Exposure to major life stressors is associated with subsequent enhanced inflammation-related disease processes. Depressive symptoms exacerbate stress-induced inflammatory responses. Moreover, those who report a high degree of perceived health risk before being exposed to a major life stressor such as a disaster are at risk for poor health outcomes. The present study examined whether perceived health risk and depressive symptoms before a disaster were associated with postdisaster inflammation markers. METHODS: The sample included 124 participants (mean [standard deviation] age = 55 [16] years; 69% women). At a baseline visit, participants completed self-report measures of perceived health risk and depressive symptoms (Center for Epidemiologic Studies Depression Scale) in addition to a blood draw for the assessment of inflammation markers (C-reactive protein, tumor necrosis factor receptor 1, and interleukin 6). All participants lived near a large petrochemical complex where an unexpected explosion occurred. A second blood sample was obtained 2 to 6 months after the explosion. RESULTS: No significant differences in inflammation markers were found between predisaster and postdisaster assessment (p > .21). An interaction between predisaster perceived health risk and depressive symptoms in predicting postdisaster circulating inflammation markers was identified (Cohen f = 0.051). Specifically, predisaster perceived health risk was associated with postdisaster circulating inflammation markers if predisaster depressive symptoms were greater than 8.10 on the Center for Epidemiologic Studies Depression Scale. CONCLUSIONS: These findings add to our understanding of the complex interactions between stress, depression, and immune responses. Indeed, findings provide a potential mechanism (i.e., inflammation) explaining the association between exposure to major life stressors and negative mental and physical health outcomes.

Objectively Measured Social Integration Is Associated With an Immune Risk Phenotype Following Marital Separation.

Background: Close relationships play an integral role in human development, and robust evidence links marital separation and divorce to poor health outcomes. Social integration may play a key role in this association. In many ways, the study of marital separation and divorce provides an ideal model system for a more complete understanding of the association between life stress and physical health. Purpose: The current study investigated associations among objectively measured social integration, psychological distress, and biomarkers of immune health in recently separated adults (N = 49). Methods: We collected four measures of immune functioning-interleukin-6, C-reactive protein, and antibody titers to latent cytomegalovirus and Epstein-Barr virus-that were combined to yield a viral-Immune Risk Profile. To assess how variability in social integration is associated with immunological correlates following the end of a marriage, we incorporated observational ecological momentary assessment data using a novel methodology (the Electronically Activated Recorder). Results: We found that objectively measured social behaviors are associated with concurrent viral-Immune Risk Profile scores over and above the effects of psychological distress and that psychological distress may be linked to biomarkers of immune health through social integration. Conclusions: This research expands current knowledge of biomarkers of immune health after divorce and separation and includes a new methodology for objective measures of social engagement.

Reactivation of Latent Epstein-Barr Virus: A Comparison after Exposure to Gamma, Proton, Carbon, and Iron Radiation.

Among the many stressors astronauts are exposed to during spaceflight, cosmic radiation may lead to various serious health effects. Specifically, space radiation may contribute to decreased immunity, which has been documented in astronauts during short- and long-duration missions, as evidenced by several changes in cellular immunity and plasma cytokine levels. Reactivation of latent herpes viruses, either directly from radiation of latently infected cells and/or from perturbation of the immune system, may result in disease in astronauts. Epstein‒Barr virus (EBV) is one of the eight human herpes viruses known to infect more than 90% of human adults and persists for the life of the host without normally causing adverse effects. Reactivation of several latent viruses in astronauts is well documented, although the mechanism of reactivation is not well understood. We studied the effect of four different types of radiation, (1) 137Cs gamma rays, (2) 150-MeV protons, (3) 600 MeV/n carbon ions, and (4) 600 MeV/n iron ions on the activation of lytic gene transcription and of reactivation of EBV in a latently infected cell line (Akata) at doses of 0.1, 0.5, 1.0, and 2.0 Gy. The data showed that for all doses used in this study, lytic gene transcription was induced and median viral loads were significantly higher for all types of radiation than in corresponding control samples, with the increases detected as early as four days post-exposure and generally tapering off at later time points. The viability and size of EBV-infected Akata cells were highly variable and exhibited approximately the same trend in time for all radiation types at 0.1, 0.5, 1.0, and 2.0 Gy. This work shows that reactivation of viruses can occur due to the effect of different types of radiation on latently infected cells in the absence of changes or cytokines produced in the immune system. In general, gamma rays are more effective than protons, carbon ions, and iron ions in inducing latent virus reactivation, though these high-energy particles did induce more sustained and later reactivation of EBV lytic gene transcription. These findings also challenge the common relative biological effectiveness concept that is often used in radiobiology for other end points.

Psychological, cultural and neuroendocrine profiles of risk for preterm birth.

BACKGROUND: Preterm birth remains a major obstetrical problem and identification of risk factors for preterm birth continues to be a priority in providing adequate care. Therefore, the purpose of this study was to elucidate risk profiles for preterm birth using psychological, cultural and neuroendocrine measures. METHODS: From a cross sectional study of 515 Mexican American pregnant women at 22-24 weeks gestation, a latent profile analysis of risk for preterm birth using structural equation modeling (SEM) was conducted. We determined accurate gestational age at delivery from the prenatal record and early ultrasounds. We also obtained demographic and prenatal data off of the chart, particularly for infections, obstetrical history, and medications. We measured depression (Beck Depression Inventory), mastery (Mastery scale), coping (The Brief Cope), and acculturation (Multidimensional Acculturation Scale) with reliable and valid instruments. We obtained maternal whole blood and separated it into plasma for radioimmunoassay of Corticotrophin Releasing Hormone (CRH). Delivery data was obtained from hospital medical records. RESULTS: Using a latent profile analysis, three psychological risk profiles were identified. The "low risk" profile had a 7.7% preterm birth rate. The "moderate risk" profile had a 12% preterm birth rate. The "highest risk" profile had a 15.85% preterm birth rate. The highest risk profile had double the percentage of total infections compared to the low risk profile. High CRH levels were present in the moderate and highest risk profiles. CONCLUSION: These risk profiles may provide a basis for screening for Mexican American women to predict risk of preterm birth, particularly after they are further validated in a prospective cohort study. Future research might include use of such an identified risk profile with targeted interventions tailored to the Hispanic culture.

Terrestrial stress analogs for spaceflight associated immune system dysregulation.

Recent data indicates that dysregulation of the immune system occurs and persists during spaceflight. Impairment of immunity, especially in conjunction with elevated radiation exposure and limited clinical care, may increase certain health risks during exploration-class deep space missions (i.e. to an asteroid or Mars). Research must thoroughly characterize immune dysregulation in astronauts to enable development of a monitoring strategy and validate any necessary countermeasures. Although the International Space Station affords an excellent platform for on-orbit research, access may be constrained by technical, logistical vehicle or funding limitations. Therefore, terrestrial spaceflight analogs will continue to serve as lower cost, easier access platforms to enable basic human physiology studies. Analog work can triage potential in-flight experiments and thus result in more focused on-orbit studies, enhancing overall research efficiency. Terrestrial space analogs generally replicate some of the physiological or psychological stress responses associated with spaceflight. These include the use of human test subjects in a laboratory setting (i.e. exercise, bed rest, confinement, circadian misalignment) and human remote deployment analogs (Antarctica winterover, undersea, etc.) that incorporate confinement, isolation, extreme environment, physiological mission stress and disrupted circadian rhythms. While bed rest has been used to examine the effects of physical deconditioning, radiation and microgravity may only be simulated in animal or microgravity cell culture (clinorotation) analogs. This article will characterize the array of terrestrial analogs for spaceflight immune dysregulation, the current evidence base for each, and interpret the analog catalog in the context of acute and chronic stress.

Anti-cytomegalovirus antibody levels stratify human immune profiles across the lifespan.

Human cytomegalovirus (hCMV) is a ubiquitous latent persistent herpesvirus infecting 60-90% of the population worldwide. hCMV carriage in immunocompetent people is asymptomatic; thus, hCMV can be considered a component of normative aging. However, hCMV powerfully modulates many features of the immune, and likely other, systems and organs. Questions remain as to how hCMV carriage affects the human host. We used anti-CMV antibody titers as a stratifying criterion to examine the impact of "intensity" of hCMV infection as a potential biomarker of aging, inflammation, and immune homeostasis in a cohort of 247 participants stratified into younger (21-40 years) and older (> 65 years of age) groups. We showed that anti-CMV antibody titers increased with age and directly correlated to increased levels of soluble tumor necrosis factor (sTNFR) I in younger but not older participants. CD8 + cell numbers were reduced in the older group due to the loss in CD8 + T naïve (Tn) cells. In CMV carriers and, in particular, in anti-CMV Ab-high participants, this loss was mitigated or reversed by an increase in the numbers of CD8 + T effector memory (Tem) and T effector memory reexpressing CD45RA (Temra) cells. Analysis of CD38, HLA-DR, and CD57 expression revealed subset (CD4 or CD8)-specific changes that correlated with anti-CMV Ab levels. In addition, anti-CMV Ab levels predicted anti-CMV CD8 T cell responsiveness to different CMV open reading frames (ORFs) selectively in older participants, which correlated to the transcriptional order of expression of specific CMV ORFs. Implications of these results for the potential predictive value of anti-CMV Ab titers during aging are discussed.

Characterization of Epstein-Barr virus reactivation in a modeled spaceflight system.

Epstein-Barr virus (EBV) is the causative agent of mononucleosis and is also associated with several malignancies, including Burkitt's lymphoma, Hodgkin's lymphoma, and nasopharyngeal carcinoma, among others. EBV reactivates during spaceflight, with EBV shedding in saliva increasing to levels ten times those observed pre-and post-flight. Although stress has been shown to increase reactivation of EBV, other factors such as radiation and microgravity have been hypothesized to contribute to reactivation in space. We used a modeled spaceflight environment to evaluate the influence of radiation and microgravity on EBV reactivation. BJAB (EBV-negative) and Raji (EBV-positive) cell lines were assessed for viability/apoptosis, viral antigen and reactive oxygen species expression, and DNA damage and repair. EBV-infected cells did not experience decreased viability and increased apoptosis due to modeled spaceflight, whereas an EBV-negative cell line did, suggesting that EBV infection provided protection against apoptosis and cell death. Radiation was the major contributor to EBV ZEBRA upregulation. Combining modeled microgravity and radiation increased DNA damage and reactive oxygen species while modeled microgravity alone decreased DNA repair in Raji cells. Additionally, EBV-infected cells had increased DNA damage compared to EBV-negative cells. Since EBV-infected cells do not undergo apoptosis as readily as uninfected cells, it is possible that virus-infected cells in EBV seropositive individuals may have an increased risk to accumulate DNA damage during spaceflight. More studies are warranted to investigate this possibility.

Immune system dysregulation occurs during short duration spaceflight on board the space shuttle.

BACKGROUND: Post-flight data suggests immunity is dysregulated immediately following spaceflight, however this data may be influenced by the stress effects of high-G entry and readaptation to terrestrial gravity. It is unknown if immunity is altered during spaceflight. METHODS: Blood samples were collected from 19 US Astronauts onboard the Space Shuttle ~24 h prior to landing and returned for terrestrial analysis. Assays consisted of leukocyte distribution, T cell blastogenesis and cytokine production profiles. RESULTS: Most bulk leukocyte subsets (WBC, differential, lymphocyte subsets) were unaltered during spaceflight, but were altered following landing. CD8+ T cell subsets, including cytotoxic, central memory and senescent were altered during spaceflight. T cell early blastogenesis varied by culture mitogen. Functional responses to staphylococcal enterotoxin were reduced during and following spaceflight, whereas response to anti-CD3/28 antibodies was elevated post-flight. The level of virus specific T cells were generally unaltered, however virus specific T cell function was depressed both during and following flight. Plasma levels of IFNα, IFNγ, IL-1ß, IL-4, IL-10, IL-12, and TNFα were significantly elevated in-flight, while IL-6 was significantly elevated at R + 0. Cytokine production profiles following mitogenic stimulation were significantly altered both during, and following spaceflight. Specifically, production of IFNγ, IL-17 and IL-10 were reduced, but production of TNFα and IL-8 were elevated during spaceflight. CONCLUSIONS: This study indicates that specific parameters among leukocyte distribution, T cell function and cytokine production profiles are altered during flight. These findings distinguish in-flight dysregulation from stress-related alterations observed immediately following landing.

Reactivation of herpes simplex virus type 1 is associated with cytomegalovirus and age.

Recent studies have shown that cytomegalovirus (CMV) may be an emerging marker of immunosenescence. CMV can affect the immune system by directly infecting leukocytes and hematopoietic cells or by eliciting an expansion of oligoclonal CD8+ T cells/contraction of the naïve T cell compartment that may reduce the host's ability to fight other pathogens. To investigate further CMV-associated changes in immunity, a study was conducted with 1,454 adults (ages 25-91) to determine the association between CMV and reactivation of another latent herpesvirus, Herpes simplex virus type 1 (HSV-1), as indexed by antibody titers. Elevated antibody titers to latent HSV-1 were significantly associated with both CMV seropositivity and high CMV antibody levels. Evaluation by specific age groups (<45, 45-64, and 65+ years old) revealed that this association was detectable early in life (<45 years of age). Increases in HSV-1 antibodies by age occurred in CMV seropositive individuals but not CMV seronegative subjects. Within CMV seropositive subjects, increases in HSV-1 antibodies by age were only found in individuals with low CMV antibody levels as those with high CMV antibodies already exhibited elevated HSV-1 antibodies. These associations remained significant after accounting for body mass index, gender, and socioeconomic status. These results suggest that CMV can influence the immune response to another pathogen and support the concept that CMV may accelerate immunosenescence.

Immune system inflammation in cocaine dependent individuals: implications for medications development.

OBJECTIVES: Cocaine dependence is a chronic stress state. Furthermore, both stress and substance abuse have robust and reciprocal effects on immune system cytokines, which are known to be powerful modulators of mood. We therefore examine basal and provoked changes in peripheral cytokines in cocaine dependent individuals to better understand their role in the negative reinforcing effects of cocaine. METHODS: Twenty-eight (16 F/12 M) treatment-seeking cocaine dependent individuals and 27 (14 F/13 M) social drinkers were exposed to three 5-min guided imagery conditions (stress, drug cue, relaxing) presented randomly across consecutive days. Measures of salivary cortisol, tumor necrosis factor alpha (TNFα), interleukin-10 (IL-10), and interleukin-1 receptor antagonist (IL-1ra) were collected at baseline and various post-imagery time-points. RESULTS: Cocaine abusers demonstrated decreased basal IL-10 compared with social drinkers. They also showed significant elevations in pro-inflammatory TNFα when exposed to stress compared with when they were exposed to relaxing imagery. This was not observed in the social drinkers. Conversely, social drinkers demonstrated increases in the anti-inflammatory markers, IL-10 and IL-1ra, following exposure to cue, which were not seen in the dependent individuals. CONCLUSIONS: Cocaine dependent individuals demonstrate an elevated inflammatory state both at baseline and following exposure to the stress imagery condition. Cytokines may reflect potentially novel biomarkers in addicted populations for treatment development.

Inflammatory and immune markers in HIV-infected older adults on long-term antiretroviral therapy: Persistent elevation of sCD14 and of proinflammatory effector memory T cells.

HIV-positive patients whose viral loads are successfully controlled by active antiretroviral therapy (ART) show no clinical signs of AIDS. However, their lifespan is shorter compared with individuals with no HIV infection and they prematurely exhibit a multitude of chronic diseases typically associated with advanced age. It was hypothesized that immune system aging may correlate with, and provide useful biomarkers for, this premature loss of healthspan in HIV-positive subjects. Here, we tested whether the immune correlates of aging, including cell numbers and phenotypes, inflammatory status, and control of human cytomegalovirus (hCMV) in HIV-positive subjects on long-term successful ART (HIV+) may reveal increased "immunological age" compared with HIV-negative, age-matched cohort (HIV-) in participants between 50 and 69 years of age. Specifically, we expected that younger HIV+ subjects may immunologically resemble older individuals without HIV. We found no evidence to support this hypothesis. While T cells from HIV+ participants displayed differential expression in several differentiation and/or inhibitory/exhaustion markers in different T cell subpopulations, aging by a decade did not pronounce these changes. Similarly, while the HIV+ participants exhibited higher T cell responses and elevated inflammatory marker levels in plasma, indicative of chronic inflammation, this trait was not age-sensitive. We did find differences in immune control of hCMV, and, more importantly, a sustained elevation of sCD14 and of proinflammatory CD4 and CD8 T cell responses across age groups, pointing towards uncontrolled inflammation as a factor in reduced healthspan in successfully treated older HIV+ patients.

Human Health during Space Travel: State-of-the-Art Review.

The field of human space travel is in the midst of a dramatic revolution. Upcoming missions are looking to push the boundaries of space travel, with plans to travel for longer distances and durations than ever before. Both the National Aeronautics and Space Administration (NASA) and several commercial space companies (e.g., Blue Origin, SpaceX, Virgin Galactic) have already started the process of preparing for long-distance, long-duration space exploration and currently plan to explore inner solar planets (e.g., Mars) by the 2030s. With the emergence of space tourism, space travel has materialized as a potential new, exciting frontier of business, hospitality, medicine, and technology in the coming years. However, current evidence regarding human health in space is very limited, particularly pertaining to short-term and long-term space travel. This review synthesizes developments across the continuum of space health including prior studies and unpublished data from NASA related to each individual organ system, and medical screening prior to space travel. We categorized the extraterrestrial environment into exogenous (e.g., space radiation and microgravity) and endogenous processes (e.g., alteration of humans' natural circadian rhythm and mental health due to confinement, isolation, immobilization, and lack of social interaction) and their various effects on human health. The aim of this review is to explore the potential health challenges associated with space travel and how they may be overcome in order to enable new paradigms for space health, as well as the use of emerging Artificial Intelligence based (AI) technology to propel future space health research.

Latent and lytic Epstein-Barr virus gene expression in the peripheral blood of astronauts.

Epstein-Barr virus (EBV) latent and replicative gene transcription was analyzed in peripheral blood B-lymphocytes from astronauts who flew on short-duration (∼11 days) Shuttle missions and long-duration (∼180 days) International Space Station (ISS) missions. Latent, immediate-early, and early gene replicative viral transcripts were detected in samples from six astronauts who flew on short-duration Shuttle missions, whereas viral gene transcription was mostly absent in samples from 24 healthy donors. Samples from six astronauts who flew on long-duration ISS missions were characterized by expanded expression of latent, immediate-early, and early gene transcripts and new onset expression of late replicative transcription upon return to Earth. These data indicate that EBV-infected cells are no longer expressing the restricted set of viral genes that characterize latency but are expressing latent and lytic gene transcripts. These data also suggest the possibility of EBV-related complications in future long-duration missions, in particular interplanetary travel.

Adrenocortical and immune responses following short- and long-duration spaceflight.

INTRODUCTION: Short-term spaceflight is associated with significant but reversible immunological alterations. However, little information exists on the effects of long-duration spaceflight on neuroimmune responses. METHODS: We collected multiple pre- and postflight samples from Shuttle and International Space Station (ISS) crewmembers in order to compare adrenocortical and immune responses between short- (approximately 11 d) and long-duration (approximately 180 d) spaceflight. RESULTS: In Shuttle crewmembers, increased stress hormone levels and altered leukocyte subsets were observed prior to launch and at landing. Additionally, typical stress-induced shifts in leukocyte and lymphocyte subsets, as well as the percentage of T-cells capable of producing intracellular IFN-gamma were also decreased just before launch and immediately after landing. Plasma IL-10 levels were increased before launch but not postflight. No preflight changes occurred in ISS crewmembers, but long-duration crewmembers exhibited significantly greater spikes in both plasma and urinary cortisol at landing as compared to Shuttle crewmembers. The percentage of T-cells capable of producing intracellular IFN-gamma was decreased in ISS crewmembers. Plasma IL-10 was increased postflight. Unexpectedly, stress-induced shifts in lymphocyte subpopulations were absent after long-duration flights despite significantly increased stress hormones at landing. CONCLUSION: Our results demonstrate significant differences in neuroimmune responses between astronauts flying on short-duration Shuttle missions versus long-duration ISS missions, and they agree with prior studies demonstrating the importance of mission duration in the magnitude of these changes.