Cold pressor stress effects on cardiac repolarization.

The cold pressor test (CPT) elicits strong cardiovascular reactions via activation of the sympathetic nervous system (SNS), yielding subsequent increases in heart rate (HR) and blood pressure (BP). However, little is known on how exposure to the CPT affects cardiac ventricular repolarization. Twenty-eight healthy males underwent both a bilateral feet CPT and a warm water (WW) control condition on two separate days, one week apart. During pre-stress baseline and stress induction cardiovascular signals (ECG lead II, Finometer BP) were monitored continuously. Salivary cortisol and subjective stress ratings were assessed intermittently. Corrected QT (QTc) interval length and T-wave amplitude (TWA) were assessed for each heartbeat and subsequently aggregated individually over baseline and stress phases, respectively. CPT increases QTc interval length and elevates the TWA. Stress-induced changes in cardiac repolarization are only in part and weakly correlated with cardiovascular and cortisol stress-reactivity. Besides its already well-established effects on cardiovascular, endocrine, and subjective responses, CPT also impacts on cardiac repolarization by elongation of QTc interval length and elevation of TWA. CPT effects on cardiac repolarization share little variance with the other indices of stress reactivity, suggesting a potentially incremental value of this parameter for understanding psychobiological adaptation to acute CPT stress.

Double hydrophilic copolymers - synthetic approaches, architectural variety, and current application fields.

Solubility and functionality of polymeric materials are essential properties determining their role in any application. In that regard, double hydrophilic copolymers (DHC) are typically constructed from two chemically dissimilar but water-soluble building blocks. During the past decades, these materials have been intensely developed and utilised as, e.g., matrices for the design of multifunctional hybrid materials, in drug carriers and gene delivery, as nanoreactors, or as sensors. This is predominantly due to almost unlimited possibilities to precisely tune DHC composition and topology, their solution behavior, e.g., stimuli-response, and potential interactions with small molecules, ions and (nanoparticle) surfaces. In this contribution we want to highlight that this class of polymers has experienced tremendous progress regarding synthesis, architectural variety, and the possibility to combine response to different stimuli within one material. Especially the implementation of DHCs as versatile building blocks in hybrid materials expanded the range of water-based applications during the last two decades, which now includes also photocatalysis, sensing, and 3D inkjet printing of hydrogels, definitely going beyond already well-established utilisation in biomedicine or as templates.

Triple-Responsive Polyampholytic Graft Copolymers as Smart Sensors with Varying Output.

Three triggers result in two measurable outputs from polymeric sensors: multiresponsive polyampholytic graft copolymers respond to pH-value and temperature, as well as the type and concentration of metal cations and therefore, allow the transformation of external triggers into simply measurable outputs (cloud point temperature (TCP ) and surface plasmon resonance (SPR) of encapsulated silver nanoparticles). The synthesis relies on poly(dehydroalanine) (PDha) as the reactive backbone and gives straightforward access to materials with tunable composition and output. In particular, a rather high sensitivity toward the presence of Cu2+ , Co2+ , and Pb2+ metal cations is found.

Cytomegalovirus Genetic Diversity Following Primary Infection.

BACKGROUND: Infection with multiple cytomegalovirus (CMV) strains (mixed infection) was reported in a variety of hosts. As the virus genetic diversity in primary CMV infection and the changes over time remain incompletely defined, we examined CMV diversity and changes in diversity over time in healthy adolescent females who participated in a phase 2 CMV gB/MF59 vaccine trial. METHODS: CMV genetic diversity was determined by genotyping of 5 genes-gB (UL55), gH (UL75), gN (UL73), US28, and UL144-in urine, saliva, and plasma samples from 15 study subjects. RESULTS: At the time of primary infection, 5 of 12 (42%) urine samples had multiple virus strains, and 50% of vaccine recipients were infected with gB1 genotype (vaccine strain). Mixed infection was documented in all 15 subjects within 3 months after primary infection, and the majority had different CMV genotypes in different compartments. Changes in genotypes over time were observed in all subjects. CONCLUSIONS: Infection with multiple CMV genotypes was common during primary infection and further diversification occurred over time. Infection with gB1 genotype in vaccine recipients suggests a lack of strain-specific protection from the vaccine. As only 5 polymorphic genes were assessed, this study likely underestimated the true genetic diversity in primary CMV infection.

AS03-Adjuvanted H5N1 Avian Influenza Vaccine Modulates Early Innate Immune Signatures in Human Peripheral Blood Mononuclear Cells.

BACKGROUND: Adjuvant System 03 (AS03) markedly enhances responses to influenza A/H5N1 vaccines, but the mechanisms of this enhancement are incompletely understood. METHODS: Using ribonucleic acid sequencing on peripheral blood mononuclear cells (PBMCs) from AS03-adjuvanted and unadjuvanted inactivated H5N1 vaccine recipients, we identified differentially expressed genes, enriched pathways, and genes that correlated with serologic responses. We compared bulk PBMC findings with our previously published assessments of flow-sorted immune cell types. RESULTS: AS03-adjuvanted vaccine induced the strongest differential signals on day 1 postvaccination, activating multiple innate immune pathways including interferon and JAK-STAT signaling, Fcγ receptor (FcγR)-mediated phagocytosis, and antigen processing and presentation. Changes in signal transduction and immunoglobulin genes predicted peak hemagglutinin inhibition (HAI) titers. Compared with individual immune cell types, activated PBMC genes and pathways were most similar to innate immune cells. However, several pathways were unique to PBMCs, and several pathways identified in individual cell types were absent in PBMCs. CONCLUSIONS: Transcriptomic analysis of PBMCs after AS03-adjuvanted H5N1 vaccination revealed early activation of innate immune signaling, including a 5- to 8-fold upregulation of FcγR1A/1B/1C genes. Several early gene responses were correlated with HAI titer, indicating links with the adaptive immune response. Although PBMCs and cell-specific results shared key innate immune signals, unique signals were identified by both approaches.

Bioimpedance Spectroscopy Imprecisely Assesses Lean Body Mass in Pediatric Dialysis Patients.

OBJECTIVES: Alterations in body compositions are strongly associated with poor outcomes in end-stage renal disease patients. Hence, assessment of lean body mass is crucial for clinically monitoring these patients. The use of multifrequency bioimpedance spectroscopy measurements has also been advocated, but their usefulness in children is questioned. We investigated whether their application is appropriate for lean body mass measurement in pediatric patients receiving chronic dialysis. METHODS: Lean body mass estimates as assessed by multifrequency bioimpedance spectroscopy and by deuterium dilution were obtained for 15 patients (mean age 10.9 ±â€Š3.6 years). RESULTS: Lean body mass (mean ±â€Šstandard deviation) determined by bioimpedance was 24.2 ±â€Š10.7 and 24.4 ±â€Š10.3 kg by deuterium technique. Bland-Altman analysis showed a mean (±standard deviation) difference between the 2 methods of -0.25 ±â€Š2.30 kg with 95% limits of agreement of -4.80 to 4.25 kg. In a multiple linear regression model, the hydration status was associated with measurement bias after adjusting for age, sex, weight, and body surface area. CONCLUSIONS: Our results show a high level of agreement between measurements by bioimpedance and deuterium technique, but the limits of agreement were wide. These findings do not support the use of bioimpedance to individually assess lean body mass in pediatric dialysis patients with and without overhydration.

Influence of the Headgroup of Azolium-Based Lipids on Their Biophysical Properties and Cytotoxicity.

A series of (un-)charged NHC derivatives bearing two pentadecyl chains in the backbone was studied in detail to find cooperative effects between the membrane and the NHC derivative. The tendency to show lipid-like behavior is dependent on the properties of the NHC derivative headgroup, which can be modified on demand. The surface activity was investigated by film balance measurements, epifluorescence microscopy, and differential scanning calorimetry. Additionally the cytotoxicity was evaluated against different cell lines such as eukaryotic tumor cell lines. These novel lipid-like NHC derivatives offer a broad spectrum for biological applications.

PlanHab study: assessment of psycho-neuroendocrine function in male subjects during 21 d of normobaric hypoxia and bed rest.

Immobilization and hypoxemia are conditions often seen in patients suffering from severe heart insufficiency or primary pulmonary diseases (e.g. fibrosis, emphysema). In future planned long-duration and exploration class space missions (including habitats on the moon and Mars), healthy individuals will encounter such a combination of reduced physical activity and oxygen tension by way of technical reasons and the reduced gravitational forces. These overall unconventional extraterrestrial conditions can result in yet unknown consequences for the regulation of stress-permissive, psycho-neuroendocrine responses, which warrant appropriate measures in order to mitigate foreseeable risks. The Planetary Habitat Simulation Study (PlanHab) investigated these two space-related conditions: bed rest as model of reduced gravity and normobaric hypoxia, with the aim of examining their influence on psycho-neuroendocrine responses. We hypothesized that both conditions independently increase measures of psychological stress and enhance neuroendocrine markers of stress, and that these effects would be exacerbated by combined treatment. The cross-over study composed of three interventions (NBR, normobaric normoxic horizontal bed rest; HBR, normobaric hypoxic horizontal bed rest; HAMB, normobaric hypoxic ambulatory confinement) with 14 male subjects during three sequential campaigns separated by 4 months. The psychological state was determined through three questionnaires and principal neuroendocrine responses were evaluated by measuring cortisol in saliva, catecholamine in urine, and endocannabinoids in blood. The results revealed no effects after 3 weeks of normobaric hypoxia on psycho-neuroendocrine responses. Conversely, bed rest induced neuroendocrine alterations that were not influenced by hypoxia.

Tc-knirps plays different roles in the specification of antennal and mandibular parasegment boundaries and is regulated by a pair-rule gene in the beetle Tribolium castaneum.

BACKGROUND: The Drosophila larval head is evolutionarily derived at the genetic and morphological level. In the beetle Tribolium castaneum, development of the larval head more closely resembles the ancestral arthropod condition. Unlike in Drosophila, a knirps homologue (Tc-kni) is required for development of the antennae and mandibles. However, published Tc-kni data are restricted to cuticle phenotypes and Tc-even-skipped and Tc-wingless stainings in knockdown embryos. Hence, it has remained unclear whether the entire antennal and mandibular segments depend on Tc-kni function, and whether the intervening intercalary segment is formed completely. We address these questions with a detailed examination of Tc-kni function. RESULTS: By examining the expression of marker genes in RNAi embryos, we show that Tc-kni is required only for the formation of the posterior parts of the antennal and mandibular segments (i.e. the parasegmental boundaries). Moreover, we find that the role of Tc-kni is distinct in these segments: Tc-kni is required for the initiation of the antennal parasegment boundary, but only for the maintenance of the mandibular parasegmental boundary. Surprisingly, Tc-kni controls the timing of expression of the Hox gene Tc-labial in the intercalary segment, although this segment does form in the absence of Tc-kni function. Unexpectedly, we find that the pair-rule gene Tc-even-skipped helps set the posterior boundary of Tc-kni expression in the mandible. Using the mutant antennaless, a likely regulatory Null mutation at the Tc-kni locus, we provide evidence that our RNAi studies represent a Null situation. CONCLUSIONS: Tc-kni is required for the initiation of the antennal and the maintenance of the mandibular parasegmental boundaries. Tc-kni is not required for specification of the anterior regions of these segments, nor the intervening intercalary segment, confirming that Tc-kni is not a canonical 'gap-gene'. Our finding that a gap gene orthologue is regulated by a pair rule gene adds to the view that the segmentation gene hierarchies differ between Tribolium and Drosophila upstream of the pair rule gene level. In Tribolium, as in Drosophila, head and trunk segmentation gene networks cooperate to pattern the mandibular segment, albeit involving Tc-kni as novel component.

Optimal timing of oral metyrapone intake for the suppression of cold-pressor stress-induced cortisol release.

BACKGROUND: Pharmacological manipulation of cortisol levels is instrumental in elucidating mechanisms underlying acute stress effects and for distinguishing the physiological and behavioral effects of cortisol from those of the adrenergic system. Administration (oral or IV) of hydrocortisone is a direct and efficient method to elevate cortisol, and thus, frequently used in psychobiological stress research. However, lowering of cortisol (i.e. blockade of stress cortisol) requires a more sophisticated approach, such as the administration of the corticostatic compound metyrapone (MET). However, there is insufficient knowledge about the temporal dynamics of MET for the blocking of stress-induced cortisol reactivity. Thus, the present study aimed to build up an experimental protocol suitable to suppress acute behavioral stress-induced cortisol secretion by MET. METHODS: 50 healthy young men were randomly assigned to one of five treatment groups. They received 750 mg oral MET either 30 (n = 9), 45 (n = 11), or 60 (n = 10) minutes before exposure to a combined cold pressor and mental arithmetic test (stress induction), or were subjected to two different control treatments (placebo 60 min before stress (n = 10) or MET 30 min before non-stressful warm-water condition (n = 10)). Salivary cortisol concentration, hemodynamics, and subjective ratings were assessed. RESULTS: Suppression of cold stress-induced cortisol release was strongest when MET intake was scheduled 30 min prior to stress onset. Cardiovascular stress-responses and subjective ratings remained unaffected by MET. CONCLUSION: In healthy young males, 750 mg of MET efficiently block cold stress-induced cortisol release when oral administration is scheduled 30 min prior to stress onset. This finding may guide future research in improving timing of suppression of stress-induced cortisol secretion.

Evaluation of the Immune Response to Chitosan-graft-poly(caprolactone) Biopolymer Scaffolds.

Biomimetic scaffolds recreating key elements of the architecture and biological activity of the extracellular matrix have enormous potential for soft tissue engineering applications. Combining appropriate mechanical properties with select biological cues presents a challenge for bioengineering, as natural materials are most bioactive but can lack mechanical integrity, while synthetic polymers have strength but are often biologically inert. Blends of synthetic and natural materials, aiming to combine the benefits of each, have shown promise but inherently require a compromise, diluting down favorable properties in each polymer to accommodate the other. Here, we electrospun a material comprising chitosan, a natural polysaccharide, and polycaprolactone (PCL), one of the most widely studied synthetic polymers used in materials engineering. In contrast to a classical blend, here PCL was chemically grafted onto the chitosan backbone to create chitosan-graft-polycaprolactone (CS-g-PCL) and then combined further with unmodified PCL to generate scaffolds with discreet chitosan functionalization. These small amounts of chitosan led to significant changes in scaffold architecture and surface chemistry, reducing the fiber diameter, pore size, and hydrophobicity. Interestingly, all CS-g-PCL-containing blends were stronger than control PCL, though with reduced elongation. In in vitro assessments, increasing the CS-g-PCL content led to significant improvements in in vitro blood compatibility compared to PCL alone while increasing fibroblast attachment and proliferation. In a mouse subcutaneous implantation model, a higher CS-g-PCL content improved the immune response to the implants. Macrophages in tissues surrounding CS-g-PCL scaffolds decreased proportionately to the chitosan content by up to 65%, with a corresponding decrease in pro-inflammatory cytokines. These results suggest that CS-g-PCL is a promising hybrid material comprising natural and synthetic polymers with tailorable mechanical and biological properties, justifying further development and in vivo evaluation.

Stressed in afterthought: Neuroendocrine effects of social self-threat during physical effort are counteracted by performance feedback after stress exposure.

Social self-threat during physical stress, such as exposure to the cold pressor test and isometric handgrip test, has been shown to induce activation of the HPA axis, in addition to autonomic responses. However, previous research has suggested that dysfunctional post-event processing may play a major role in neuroendocrine reactivity at initial as well as subsequent social stress exposure. In the present study, we investigated how the interplay of context (i.e. performance feedback) with state (i.e., self-esteem) as well as trait-like factors (i.e., ruminative tendencies) affects stress responses to repeated, short bouts of physical activity. On two sessions, 1 week apart, 53 participants (27 women) performed an isometric handgrip task for 3 min, during which they were exposed to social-evaluative threat. In addition, participants received fake feedback on their performance immediately after the task, labeling it as either 'above' (positive) or 'below average' (negative). In addition to neuroendocrine (cortisol), cardiovascular (heart rate, blood pressure) and subjective stress reactivity, performance-related and social dimensions of state self-esteem were assessed before and after stress induction. Substantial increases in cardiovascular parameters were found on both days, regardless of feedback condition. However, positive feedback led to significantly diminished neuroendocrine responses on day 1, whereas baseline cortisol on session 2 was significantly higher in the negative feedback group. Conversely, social self-esteem decreased after stress induction on both days only for participants who had received negative feedback. Changes in self-esteem reported on day 1 were associated with increased baseline cortisol at the second session, while interindividual differences in self-reported (trait) rumination were associated with cortisol reactivity at session 1. Taken together, the results suggest that effects of social evaluation during short periods of physical stress rely on post-event processing and might be counteracted by positive appraisal directly after stress exposure. Post-hoc framing (in terms of success vs. failure) may predict subsequent stress-related hormonal effects better than task demands per se, which should be considered as a potential moderator in future acute stress research, but might also be relevant to many practical applications in fields ranging from sports/performance to health psychology.

Diagnostic prediction models for CT-confirmed and bacterial rhinosinusitis in primary care: individual participant data meta-analysis.

BACKGROUND: Antibiotics are overused in patients with acute rhinosinusitis (ARS) as it is difficult to identify those who benefit from antibiotic treatment. AIM: To develop prediction models for computed tomography (CT)-confirmed ARS and culture-confirmed acute bacterial rhinosinusitis (ABRS) in adults presenting to primary care with symptoms suggestive of ARS. DESIGN AND SETTING: This was a systematic review and individual participant data meta-analysis. METHOD: CT-confirmed ARS was defined as the presence of fluid level or total opacification in any maxillary sinuses, whereas culture-confirmed ABRS was defined by culture of fluid from antral puncture. Prediction models were derived using logistic regression modelling. RESULTS: Among 426 patients from three studies, 140 patients (32.9%) had CT-confirmed ARS. A model consisting of seven variables: previous diagnosis of ARS, preceding upper respiratory tract infection, anosmia, double sickening, purulent nasal discharge on examination, need for antibiotics as judged by a physician, and C-reactive protein (CRP) showed an optimism-corrected c-statistic of 0.73 (95% confidence interval [CI] = 0.69 to 0.78) and a calibration slope of 0.99 (95% CI = 0.72 to 1.19). Among 225 patients from two studies, 68 patients (30.2%) had culture-confirmed ABRS. A model consisting of three variables: pain in teeth, purulent nasal discharge, and CRP showed an optimism-corrected c-statistic of 0.70 (95% CI = 0.63 to 0.77) and a calibration slope of 1.00 (95% CI = 0.66 to 1.52). Clinical utility analysis showed that both models could be useful to rule out the target condition. CONCLUSION: Simple prediction models for CT-confirmed ARS and culture-confirmed ABRS can be useful to safely reduce antibiotic use in adults with ARS in high-prescribing countries.

Insect Antiadhesive Surfaces Using Electrosprayed Wrinkled Ethyl Cellulose Particles.

A range of plants developed leaves, the surfaces of which prevent or diminish insect adhesion due to their microscopic topography. Well known examples include the leaves of the lychee tree (Litchi chinensis). Here, we report a method to coat substrates with ethyl cellulose microparticles that exhibit wrinkled surfaces, resulting in surface morphologies that closely resemble those of insect repelling plants, i.e., Litchi chinensis. The microparticles were prepared by electrospraying, a method that allowed tuning of the particle size and surface morphology. By measuring the traction forces of Colorado potato beetles walking on these surfaces, the wrinkly microsphere parameters were optimized, resulting in biomimetic surfaces that surpass the antiadhesive properties of the biological role model. This study may pave the way to sustainable, nontoxic insecticide replacements.

The treatment of periprosthetic fractures with locking plates: effect of drill and screw type on cement mantles: a biomechanical analysis.

INTRODUCTION: Periprosthetic fractures after cemented hip replacement are a challenging problem to manage. Biomechanical studies have suggested the benefit of using locking screws for plate fixation, but there are concerns whether screws damage the cement mantle and promote crack propagation leading to construct failure. METHOD: In this biomechanical study, different screw types were implanted into the cement mantle after pre-drilling holes of different sizes, in unicortical and bicortical configuration. The presence of cracks and the pull-out resistance of these screws were then evaluated. RESULTS: No unicortical screw induced cracks. Screws with a shortened tip, smaller flutes and double threads were significantly better for pull-out resistance. Bicortical screws were associated with a risk of local cement mantle damage, but also with a significantly greater holding power. By increasing the drill diameter, the onset of cracks decreased, but so does the pull-out resistance.

Early detection and efficient therapy of cardiac angiosarcoma due to routine transesophageal echocardiography after cerebrovascular stroke.

Primary malignant cardiac tumors (cardiac angiosarcomas) are exceedingly rare. Since there are initially nonspecific or missing symptoms, these tumors are usually diagnosed only in an advanced, often incurable stage, after the large tumor mass elicits hemodynamic obstructive symptoms. A 59-year-old female presented with symptoms of cerebral ischemia. A computed tomography (CT) scan showed changes suggestive of stroke. Transesophageal echocardiography revealed an inhomogeneous, medium-echogenic, floating mass at the roof of the left atrium near the mouth of the right upper pulmonary vein, indicative of a thrombus. At surgery, a solitary tumor was completely enucleated. Histologically, cardiac angiosarcoma was diagnosed. The patient received adjuvant chemotherapy and was free of symptoms and recurrence of disease at 14 months follow-up. Due to the fortuitous appearance of clinical signs indicative of stroke, cardiac angiosarcoma was diagnosed and effectively treated at an early, nonmetastatic, and therefore potentially curable stage. Although cardiac angiosarcoma is a rare disease, it should be taken into consideration as a potential cause of cerebral embolic disease.

Acute stress enhances pupillary responses to erotic nudes: Evidence for differential effects of sympathetic activation and cortisol.

Chronic stress attenuates reproductive behavior in many species, but evidence regarding the impact of acute stress on human sexual arousability is insufficient. Stressor-specific effects might result from divergent roles of both stress response systems. Social self-threat, linked to affiliation-oriented coping, might also influence sexual responsivity. To investigate stress-induced modulation of the processing of sexual cues and its relationship with cortisol, 58 participants underwent either a predominantly sympathetic stressor (3 min sustained handgrip) or similar control procedure. In both conditions, half of the sample was monitored by an opposite-sex person (social evaluation). Pupillary responses to erotic nudes were recorded and dissociated into fast and slow PCA components. Physically stressed participants showed enhanced (slow) dilation to explicit pictures. Cortisol levels after stress negatively predicted rapid responses to opposite-sex and (marginally) explicit stimuli. Our results suggest that acute sympathetic stress exposure facilitates cognitive sexual processing, whereas subsequent HPA-axis activation may induce counteracting effects.

Pre-analytical factors related to the stability of ethanol concentration during storage of ante-mortem blood alcohol specimens.

Sterile ante-mortem blood specimens were spiked with ethanol at the South African blood alcohol legal concentration limits of 0.20 g/L and 0.50 g/L and were stored in tubes containing sodium fluoride over a period of twenty-nine weeks under refrigeration (4 °C) and at room temperature (22 °C) to study the stability of the ethanol concentrations over time. Those stored under refrigeration were found to be stable, while a significant decrease in ethanol concentration at 99% confidence was observed in those stored at room temperature. Additional blood specimens, also spiked with ethanol, were inoculated with the dimorphic fungus Candida albicans at five different levels (1 × 106 cells/mL, 5 × 105 cells/mL, 1 × 104 cells/mL, 5 × 103 cells/mL and 5 × 101 cells/mL) and stored with and without sodium fluoride at 4 °C and 22 °C. The ethanol concentrations were monitored for nine weeks unless no fungal colonies were detected. Regardless of the presence or absence of NaF in samples - sterile or otherwise - storing specimens at 4 °C was sufficient to maintain the integrity of blood alcohol concentrations. The ethanol analyses were performed with an in-house validated isotope dilution gas chromatography-mass spectrometry analytical method on newly opened specimens once a week after which significance testing was performed to draw conclusions regarding changes in ethanol concentrations with measurement uncertainty in mind.

The socially evaluated handgrip test: Introduction of a novel, time-efficient stress protocol.

Most widely-used stress-induction procedures (such as the TSST and the Cold Pressor Test) require considerable effort and overhead in terms of preparation, logistics, and staff recruitment. Moreover, while known to reliably induce HPA axis activation, especially when combined with social self-threat, most conventional laboratory stressors cannot be flexibly adapted to elicit either a mainly autonomic or an additional endocrine stress response. Being a promising alternative approach, a new version of the isometric handgrip test enriched by a social-evaluative component was evaluated in the present study. On two consecutive sessions, forty participants (20 women) performed a handgrip task at both 45% (stress) and 10% (control) of maximum voluntary isometric contraction lasting for 3min. During the stress test, continuous visual feedback on performance was given. Participants in the social-evaluative condition (50%) were observed and evaluated by a previously unknown person of the opposite sex, whereas in the standard condition feedback was provided via a computer monitor. Cardiovascular measures (heart rate, blood pressure) as well as additional indices of autonomic reactivity (skin conductance, heart-rate variability) were registered before, during, and after stress induction. Moreover, changes in salivary cortisol and in subjective well-being were assessed. Relative to control, significant increases in cardiovascular and sympathetic activity were found, irrespective of experimental group. Importantly, however, additional social evaluation resulted in elevated cortisol levels. Furthermore, evidence for reduced vagal tone during sustained socially evaluated handgrip emerged. In conclusion, the socially evaluated handgrip test represents a versatile, time-efficient method to induce stress in small laboratory settings.

Blunted endocrine response to a combined physical-cognitive stressor in adults with early life adversity.

The negative health effects of early life adversity (ELA) continue long into adulthood. Changes in the physiological response to psychosocial stressors have been proposed to mediate this effect. However, many previous studies have come to contradicting conclusions as to whether ELA induces a long-term increase or decrease in stress reactivity. Therefore, we tested the association of ELA exposure and adult stress reactivity in a sample of early life adoptees and controls. Two previously validated stressful elements (bilateral feet CPT and the Paced Auditory Serial Addition Task (PASAT)) were combined in an extended Cold Pressor Test (CPT). This test was performed on 22 participants who had experienced severe ELA (separation from biological parents, institutionalization, and adoption in early childhood), and in 22 age-matched control participants. A prior history of ELA was associated with blunted reactivity of the hypothalamic-pituitary-adrenal (HPA) axis (Cohen´s d = 0.680). Cardiovascular reactivity remained unchanged, and affective reactivity (self-report ratings) were increased in participants exposed to ELA compared to the control group (range Cohen´s d: 0.642-0.879). Our results suggest that the activity of the HPA axis reactivity was inhibited in ELA participants. Importantly, cardiovascular stress responsiveness was not affected by ELA. This separation of the HPA axis and cardiovascular stress responses may best be explained by ELA selectively enhancing central feedback-sensitivity to glucocorticoids, but preserving cardiovascular/ autonomic stress reactivity.