The association between life events, social support, and antibody status following thymus-dependent and thymus-independent vaccinations in healthy young adults

This study determined whether stressful life events and social support were related to antibody status following both thymus-dependent and thymus-independent vaccinations. Life events in the previous year and customary social support were measured in 57 healthy students at baseline. Antibody status was also assessed at baseline and at five weeks and five months following vaccination with the trivalent influenza vaccine and the meningococcal A+C polysaccharide vaccine. Taking into account baseline antibody titre, high life events scores prior to vaccination were associated with lower responses to the B/Shangdong influenza strain at both five weeks and five months and meningococcal C at five weeks. Life events scores were not associated with response to the other two influenza viral strains nor response to meningococcal A. Those with high social support scores had stronger 5-week and 5-month antibody responses to the A/Panama influenza strain, but not to any of the other strains. These associations could not be accounted for by demographic or health behaviour factors, and also emerged from analyses comparing those who exhibited a four-fold increase in antibody titre from baseline with those who did not. Life events and social support were related to antibody status following influenza vaccination in distinctive ways that may be partly determined by vaccine novelty and prior naturalistic exposure. Life events also predicted poor antibody response to meningococcal C polysaccharide vaccination after previous meningococcal C conjugate vaccination. Neither psychosocial factor was associated with response to primary meningococcal A polysaccharide vaccination

Basic Psychological Need Satisfaction, Stress-Related Appraisals, and Dancers’ Cortisol and Anxiety Responses \ud

Self-determination theory (Deci & Ryan, 2000) posits basic psychological need satisfaction (BPNS) as essential for optimal functioning and health. Grounded in this framework, the current study examined the role of BPNS in dancers’ cognitive appraisals and hormonal and emotional responses to performance stress. Dancers reported their degree of BPNS 1 month before a solo performance. Threat and challenge appraisals of the solo were recorded 2 hr before the performance. Salivary cortisol and anxiety were measured 15 min before, and 15, 30, 45, and 60 min postperformance. Higher BPNS was associated with lower cortisol responses and anxiety intensity. Challenge appraisals mediated the association between BPNS and cortisol. Threat appraisals mediated the BPNS–anxiety intensity relationship. These findings point to the potential importance of performers’ BPNS for optimal emotional and hormonal homeostasis in performance conditions.\ud \u

A shot in the arm for research: Why are vaccinations interesting to psychologists?

First paragraph: Next time you get flu or a cold after a particularly difficult week, don’t dismiss it as coincidence. Interdisciplinary work between psychologists and immunologists has shown that factors like stress could be the trigger. By studying the response to vaccination, we can examine immune function in a clinically meaningful way. This technique has demonstrated relationships between factors such as stress, social support, and personality and vaccination-induced protection against disease. The types of stress and social support that influence our immune response also change as we age, emphasising the importance of a life course approach to study

Cardiovascular activity and the antibody response to vaccination

Objective To examine the relationship between cardiovascular activity in response to acute psychological stress and the antibody response to vaccination. Methods Fifty-seven healthy participants were vaccinated with the trivalent influenza vaccine and meningococcal A+C polysaccharides. Antibody levels were measured at baseline and 5-weeks post-vaccination. Cardiovascular activity was measured at rest, during, and following a mental arithmetic stress task in 54 participants. Results Participants demonstrating a fourfold increase in antibody titre to the A/Panama and B/Shangdong influenza strains and to meningococcal A showed greater blood pressure reactions toward the end of the acute stress task. In addition, there was some evidence of delayed diastolic blood pressure recovery in those who were responders to A/Panama and B/Shangdong influenza strains. Conclusion The present results suggest that heightened cardiovascular reactivity to stress and delayed recovery may not necessarily be detrimental to all aspects of health and may be associated with an enhanced immune response to antigen challenge

Bereavement and marriage are associated with antibody response to influenza vaccination in the elderly

Stressful life events exposure including bereavement, an event commonly experienced by elderly people, social support, marital status and satisfaction were examined in relation to antibody response to the annual trivalent influenza vaccination in an elderly community sample (N = 184). Antibody response was assessed at baseline, and at one and 12 months following vaccination. Taking into account baseline antibody titer, overall life events exposure and social support were not associated with response to any of the influenza strains. However, bereavement in the year prior to vaccination was negatively associated with the one-month response to the A/Panama and B/Shangdong strains. Being married and having higher marital satisfaction was also associated with higher peak responses to the A/Panama influenza strain at one month. The positive association between marital satisfaction and A/Panama response was particularly evident in the younger half of the married sample. These associations largely withstood adjustment for potential confounders. Thus, in the elderly, peak antibody response was associated with bereavement and marriage, and not the more general factors, life events and social support, related to antibody response in student samples. This suggests the importance of taking a life course approach to examining relationships between psychosocial factors and immunity, and that interventions to modify the impact of these factors should address those most salient for each age group

Surgical site infections after emergency hernia repair:substudy from the Management of Acutely Symptomatic Hernia (MASH) study

Introduction: Acutely symptomatic abdominal wall and groin hernias (ASH) are a common acute surgical presentation. There are limited data to guide decisions related to surgical repair technique and use of antibiotics, which can be driven by increased risk of surgical site infection (SSI) in this group. This study aims to report rates of SSI following ASH repair and explore the use of patient-reported outcome measure reporting in this setting.Methods: An 18-week, UK-based, multicentre prospective cohort study (NCT04197271) recruited adults with ASH. This study reports operatively managed patients. Data on patient characteristics, inpatient management, quality of life, complications, and wound healing (Bluebelle score) were collected. Descriptive analyses were performed to estimate event rates of SSI and regression analysis explored the relationship between Bluebelle scores and SSI. The 30 and 90-day follow-up visits assessed complications and quality of life.Results: The MASH study recruited 273 patients, of whom 218 were eligible for this study, 87.2 per cent who underwent open repair. Mesh was used in 123 patients (50.8 per cent). Pre- and postoperative antibiotics were given in 163 (67.4 per cent) and 28 (11.5 per cent) patients respectively. There were 26 reported SSIs (11.9 per cent). Increased BMI, incisional, femoral, and umbilical hernia were associated with higher rates of SSI (P = 0.006). In 238 patients, there was a difference in healthy utility values at 90 days between patients with and without SSI (P = 0.025). Also, when analysing 191 patients with Bluebelle scores, those who developed an SSI had higher Bluebelle values (P < 0.001).Conclusion: SSI is frequent in repair of acutely symptomatic hernia and correlates with BMI and site of hernia

Elevated HbA1c levels and the accumulation of differentiated T cells in CMV+ individuals

Aims/hypothesis Biological ageing of the immune system, or immunosenescence, predicts poor health and increased mortality. A hallmark of immunosenescence is the accumulation of differentiated cytotoxic T cells (CD27−CD45RA+/−; or dCTLs), partially driven by infection with the cytomegalovirus (CMV). Immune impairments reminiscent of immunosenescence are also observed in hyperglycaemia, and in vitro studies have illustrated mechanisms by which elevated glucose can lead to increased dCTLs. This study explored associations between glucose dysregulation and markers of immunosenescence in CMV+ and CMV− individuals. Methods A cross-sectional sample of participants from an occupational cohort study (n = 1,103, mean age 40 years, 88% male) were assessed for HbA1c and fasting glucose levels, diabetes, cardiovascular risk factors (e.g. lipids), numbers of circulating effector memory (EM; CD27−CD45RA−) and CD45RA re-expressing effector memory (EMRA; CD27−CD45RA+) T cells, and CMV infection status. Self-report and physical examination assessed anthropometric, sociodemographic and lifestyle factors. Results Among CMV+ individuals (n = 400), elevated HbA1c was associated with increased numbers of EM (B = 2.75, p \u3c 0.01) and EMRA (B = 2.90, p \u3c 0.01) T cells, which was robust to adjustment for age, sex, sociodemographic variables and lifestyle factors. Elevated EM T cells were also positively associated with total cholesterol (B = 0.04, p \u3c 0.05) after applying similar adjustments. No associations were observed in CMV− individuals. Conclusions/interpretation The present study identified consistent associations of unfavourable glucose and lipid profiles with accumulation of dCTLs in CMV+ individuals. These results provide evidence that the impact of metabolic risk factors on immunity and health can be co-determined by infectious factors, and provide a novel pathway linking metabolic risk factors with accelerated immunosenescence. Electronic supplementary material The online version of this article (doi:10.1007/s00125-015-3731-4) contains peer-reviewed but unedited supplementary material, which is available to authorised users

Biological effects of sodium phenylbutyrate and taurursodiol in Alzheimer's disease

INTRODUCTION: Sodium phenylbutyrate and taurursodiol (PB and TURSO) is hypothesized to mitigate endoplasmic reticulum stress and mitochondrial dysfunction, two of many mechanisms implicated in Alzheimer's disease (AD) pathophysiology. METHODS: The first‐in‐indication phase 2a PEGASUS trial was designed to gain insight into PB and TURSO effects on mechanistic targets of engagement and disease biology in AD. The primary clinical efficacy outcome was a global statistical test combining three endpoints relevant to disease trajectory (cognition [Mild/Moderate Alzheimer's Disease Composite Score], function [Functional Activities Questionnaire], and total hippocampal volume on magnetic resonance imaging). Secondary clinical outcomes included various cognitive, functional, and neuropsychiatric assessments. Cerebrospinal fluid (CSF) biomarkers spanning multiple pathophysiological pathways in AD were evaluated in participants with both baseline and Week 24 samples (exploratory outcome). RESULTS: PEGASUS enrolled 95 participants (intent‐to‐treat [ITT] cohort); cognitive assessments indicated significantly greater baseline cognitive impairment in the PB and TURSO (n = 51) versus placebo (n = 44) group. Clinical efficacy outcomes did not significantly differ between treatment groups in the ITT cohort. CSF interleukin‐15 increased from baseline to Week 24 within the placebo group (n = 34). In the PB and TURSO group (n = 33), reductions were observed in core AD biomarkers phosphorylated tau‐181 (p‐tau181) and total tau; synaptic and neuronal degeneration biomarkers neurogranin and fatty acid binding protein‐3 (FABP3); and gliosis biomarker chitinase 3‐like protein 1 (YKL‐40), while the oxidative stress marker 8‐hydroxy‐2‐deoxyguanosine (8‐OHdG) increased. Between‐group differences were observed for the Aβ42/40 ratio, p‐tau181, total tau, neurogranin, FABP3, YKL‐40, interleukin‐15, and 8‐OHdG. Additional neurodegeneration, inflammation, and metabolic biomarkers showed no differences between groups. DISCUSSION: While between‐group differences in clinical outcomes were not observed, most likely due to the small sample size and relatively short treatment duration, exploratory biomarker analyses suggested that PB and TURSO engages multiple pathophysiologic pathways in AD. Highlights: Proteostasis and mitochondrial stress play key roles in Alzheimer's disease (AD). Sodium phenylbutyrate and taurursodiol (PB and TURSO) targets these mechanisms. The PEGASUS trial was designed to assess PB and TURSO effects on biologic AD targets. PB and TURSO reduced exploratory biomarkers of AD and neurodegeneration. Supports further clinical development of PB and TURSO in neurodegenerative diseases

Rudimentary signs of immunosenescence in <em>Cytomegalovirus</em>-seropositive healthy young adults

Ageing is associated with a decline in immune competence termed immunosenescence. In the elderly, this process results in an accumulation of differentiated ‘effector’ phenotype memory T cells, predominantly driven by Cytomegalovirus (CMV) infection. Here, we asked whether CMV also drives immunity towards a senescent profile in healthy young adults. One hundred and fifty-eight individuals (mean ± SD; age 21 ± 3 years, body mass index 22.7 ± 2.7 kg m2) were assessed for CMV serostatus, the numbers/proportions of CD4+ and CD8+ late differentiated/effector memory cells (i.e. CD27−CD28−/CD45RA+), plasma interleukin-6 (IL-6) and antibody responses to an in vivo antigen challenge (half-dose influenza vaccine). Thirty percent (48/158) of participants were CMV+. A higher lymphocyte and CD8+ count (both p < 0.01) and a lower CD4/CD8 ratio (p < 0.03) were observed in CMV+ people. Eight percent (4/58) of CMV+ individuals exhibited a CD4/CD8 ratio <1.0, whereas no CMV− donor showed an inverted ratio (p < 0.001). The numbers of CD4+ and CD8+CD27−CD28−/CD45RA+ cells were ~ fourfold higher in CMV+ people (p < 0.001). Plasma IL-6 was higher in CMV+ donors (p < 0.05) and showed a positive association with the numbers of CD8+CD28− cells (p < 0.03). Finally, there was a significant negative correlation between vaccine-induced antibody responses to the A/Brisbane influenza strain and CMV-specific immunoglobulin G titres (p < 0.05). This reduced vaccination response was associated with greater numbers of total CD8+ and CD4+ and CD8+CD27−CD28−/CD45RA+ cells (p < 0.05). This study observed marked changes in the immune profile of young adults infected with CMV, suggesting that this virus may underlie rudimentary aspects of immunosenescence even in a chronologically young population