Individual differences in emotion prediction and implications for social success.

The social world requires people to predict others' thoughts, feelings, and actions. People who successfully predict others' emotions experience significant social advantages. What makes a person good at predicting emotions? To predict others' future emotional states, a person must know how one emotion transitions to the next. People learn how emotions transition from at least two sources: (a) internal information, or one's own emotion experiences, and (b) external information, such as the social cues detected in a person's face. Across five studies collected between 2018 and 2020, we find evidence that both sources of information are related to accurate emotion prediction: individuals with atypical personal emotion transitions, difficulty understanding their own emotional experiences, and impaired emotion perception displayed impaired emotion prediction. This ability to predict others' emotions has real-world social implications. Individuals who make accurate emotion predictions have better relationships with their friends and communities and experience less loneliness. In contrast, disruptions in both internal and external information sources explain prediction inaccuracy in individuals with social difficulties, specifically with social communication difficulties common in autism spectrum disorder. These findings provide evidence that successful emotion prediction, which relies on the perception of accurate internal and external data about how emotions transition, may be key to social success. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Hypoxia inhibits HUNK kinase activity to induce epithelial-mesenchymal transition.

Hypoxia is a common hallmark of cancer and plays a crucial role in promoting epithelial-mesenchymal transition (EMT). Hormonally Upregulated Neu-associated Kinase (HUNK) regulates EMT through its kinase activity. However, whether hypoxia is involved in HUNK-mediated EMT is incompletely understood. This study unveils an association between HUNK kinase activity and hypoxia in colorectal cancer (CRC). Importantly, hypoxia does not alter the expression levels of HUNK, but directly affects the phosphorylation levels of downstream proteins with indication of HUNK activity. Functionally, the upregulation of migration, invasion, and expression of EMT markers in CRC cells under hypoxic conditions can be attributed, in part, to the downregulation of HUNK-mediated phosphorylation of downstream proteins. These findings highlight the intricate relationship between HUNK, hypoxia and the molecular mechanisms of cancer EMT. Understanding these mechanisms may provide valuable insights into therapeutic targets for inhibiting cancer metastasis.

Phase-shifting the circadian glucocorticoid profile induces disordered feeding behaviour by dysregulating hypothalamic neuropeptide gene expression.

Here we demonstrate, in rodents, how the timing of feeding behaviour becomes disordered when circulating glucocorticoid rhythms are dissociated from lighting cues; a phenomenon most commonly associated with shift-work and transmeridian travel 'jetlag'. Adrenalectomized rats are infused with physiological patterns of corticosterone modelled on the endogenous adrenal secretory profile, either in-phase or out-of-phase with lighting cues. For the in-phase group, food intake is significantly greater during the rats' active period compared to their inactive period; a feeding pattern similar to adrenal-intact control rats. In contrast, the feeding pattern of the out-of-phase group is significantly dysregulated. Consistent with a direct hypothalamic modulation of feeding behaviour, this altered timing is accompanied by dysregulated timing of anorexigenic and orexigenic neuropeptide gene expression. For Neuropeptide Y (Npy), we report a glucocorticoid-dependent direct transcriptional regulation mechanism mediated by the glucocorticoid receptor (GR). Taken together, our data highlight the adverse behavioural outcomes that can arise when two circadian systems have anti-phasic cues, in this case impacting on the glucocorticoid-regulation of a process as fundamental to health as feeding behaviour. Our findings further highlight the need for development of rational approaches in the prevention of metabolic dysfunction in circadian-disrupting activities such as transmeridian travel and shift-work.

Egocentric Projection is a Rational Strategy for Accurate Emotion Prediction.

People need to accurately understand and predict others' emotions in order to build and maintain meaningful social connections. However, when they encounter new social partners, people often do not have enough information about them to make accurate inferences. Rather, they often resort to an egocentric heuristic, and make predictions about a target by using their own self-knowledge as a proxy. Is this egocentric heuristic a form of cognitive bias, or is it a rational strategy for real-world social prediction? If egocentrism provides a rational and effective solution to the challenging task of social prediction in naturalistic contexts, we should expect that a) egocentric predictions tend to be more accurate, and b) people rely on self-knowledge to a greater extent when it's more likely to be a good proxy. Using an emotion prediction task and personality measures, we assessed similarity and predictive accuracy between first-year college students and their new acquaintance roommate. Results demonstrated that, when people need to predict an unfamiliar target's emotions, self-knowledge can often effectively approximate knowledge about others, and thus support accurate predictions. Moreover, participants that were typical of the sample, whose self-knowledge can better approximate information about the target, relied more on self-knowledge in their predictions, and thus achieved higher accuracy. These findings suggest that people rationally tune their use of egocentrism based on whether it is likely to pay off. Overall, these findings demonstrate a rational side to a cognitive phenomenon usually framed as a cognitive pitfall, namely egocentric projection, when its natural decision context is taken into consideration.

Quantity and location of aortic valve calcification predicts paravalvular leakage after transcatheter aortic valve replacement: a systematic review and meta-analysis.

Introduction: Transcatheter aortic valve replacement (TAVR) is the first-line treatment for patients with moderate-to-high surgical risk of severe aortic stenosis. Paravalvular leakage (PVL) is a serious complication of TAVR, and aortic valve calcification contributes to the occurrence of PVL. This study aimed to investigate the effect of location and quantity of calcification in the aortic valve complex (AVC) and left ventricular outflow tract (LVOT) on PVL after TAVR. Method: We performed a systematic review and meta-analysis to evaluate the effect of quantity and location of aortic valve calcification on PVL after TAVR using observational studies from PubMed and EMBASE databases from inception to February 16, 2022. Results: Twenty-four observational studies with 6,846 patients were included in the analysis. A high quantity of calcium was observed in 29.6% of the patients; they showed a higher risk of significant PVL. There was heterogeneity between studies (I2 = 15%). In the subgroup analysis, PVL after TAVR was associated with the quantity of aortic valve calcification, especially those located in the LVOT, valve leaflets, and the device landing zone. A high quantity of calcium was associated with PVL, regardless of expandable types or MDCT thresholds used. However, for valves with sealing skirt, the amount of calcium has no significant effect on the incidence of PVL. Conclusion: Our study elucidated the effect of aortic valve calcification on PVL and showed that the quantity and location of aortic valve calcification can help predict PVL. Furthermore, our results provide a reference for the selection of MDCT thresholds before TAVR. We also showed that balloon-expandable valves may not be effective in patients with high calcification, and valves with sealing skirts instead of those without sealing skirts should be applied more to prevent PVL from happening. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=354630, identifier: CRD42022354630.

Single-pixel imaging with high spectral and spatial resolution.

It has long been a challenge to obtain high spectral and spatial resolution simultaneously for the field of measurement and detection. Here we present a measurement system based on single-pixel imaging with compressive sensing that can realize excellent spectral and spatial resolution at the same time, as well as data compression. Our method can achieve high spectral and spatial resolution, which is different from the mutually restrictive relationship between the two in traditional imaging. In our experiments, 301 spectral channels are obtained in the band of 420-780 nm with a spectral resolution of 1.2 nm and a spatial resolution of 1.11 mrad. A sampling rate of 12.5% for a 64×64p i x e l image is obtained by using compressive sensing, which also reduces the measurement time; thus, high spectral and spatial resolution are realized simultaneously, even at a low sampling rate.

Circadian regulation of hippocampal function is disrupted with corticosteroid treatment.

Disrupted circadian activity is associated with many neuropsychiatric disorders. A major coordinator of circadian biological systems is adrenal glucocorticoid secretion which exhibits a pronounced preawakening peak that regulates metabolic, immune, and cardiovascular processes, as well as mood and cognitive function. Loss of this circadian rhythm during corticosteroid therapy is often associated with memory impairment. Surprisingly, the mechanisms that underlie this deficit are not understood. In this study, in rats, we report that circadian regulation of the hippocampal transcriptome integrates crucial functional networks that link corticosteroid-inducible gene regulation to synaptic plasticity processes via an intrahippocampal circadian transcriptional clock. Further, these circadian hippocampal functions were significantly impacted by corticosteroid treatment delivered in a 5-d oral dosing treatment protocol. Rhythmic expression of the hippocampal transcriptome, as well as the circadian regulation of synaptic plasticity, was misaligned with the natural light/dark circadian-entraining cues, resulting in memory impairment in hippocampal-dependent behavior. These findings provide mechanistic insights into how the transcriptional clock machinery within the hippocampus is influenced by corticosteroid exposure, leading to adverse effects on critical hippocampal functions, as well as identifying a molecular basis for memory deficits in patients treated with long-acting synthetic corticosteroids.

Image-free real-time target tracking by single-pixel detection.

Image-based target tracking methods rely on continuous image acquisition and post-processing, which will result in low tracking efficiency. To realize real-time tracking of fast moving objects, we propose an image-free target tracking scheme based on the discrete cosine transform and single-pixel detection. Our method avoids calculating all the phase values, so the number of samples can be greatly reduced. Furthermore, complementary modulation is applied to reduce the measurement noise, and background subtraction is applied to enhance the contrast. The results of simulations and experiments demonstrate that the proposed scheme can accomplish the tracking task in a complex background with a sampling ratio of less than 0.59% of the Nyquist-Shannon criterion, thereby significantly reducing the measurement time. The tracking speed can reach 208 fps at a spatial resolution of 128 × 128 pixels with a tracking error of no more than one pixel. This technique provides a new idea for real-time tracking of fast-moving targets.

Accurate emotion prediction in dyads and groups and its potential social benefits.

Emotion dynamics vary considerably from individual to individual and from group to group. Successful social interactions require people to track this moving target in order to anticipate the thoughts, feelings, and actions of others. In two studies, we test whether people track others' emotional idiosyncrasies to make accurate, target-specific emotion predictions. In both studies, participants predicted the emotion transitions of a specific target-either a close friend (Study 1) or a first-year college roommate (Study 2)-as well as an average group member. Results demonstrate that people can make highly accurate predictions both for specific individuals and specific groups. Accurate predictions rely on target-specific knowledge; new community members were able to make accurate predictions at zero-acquaintance, but accuracy increased over time as individuals accrued specialized knowledge. Results also suggest that accurate emotion prediction is associated with social success in both individual and communal relationships and that such a relation might emerge over time. Overall, our studies suggest that people accurately make individualized predictions of others' emotion transitions and that doing so fulfills a meaningful function in the social world. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Flame retardant and smoke-suppressant rigid polyurethane foam based on sodium alginate and aluminum diethylphosphite.

In order to improve the flame-retardant effect and thermal behaviour of rigid polyurethane foam (RPUF), the flame retardancy of sodium alginate (SA), aluminium diethyl phosphite (ADPO2) and expandable graphite (EG) were proposed. First, the structures of RPUF with or without flame retardancy were confirmed by scanning electron microscopy (SEM). Additionally, the combustion behaviours and thermal performance of the flame-retardant polyurethane were evaluated through thermogravimetric analysis (TGA), limiting oxygen index (LOI) tests, and UL-94 tests. Finally, the cone calorimeter results reveled the RPUF/5ADPO2/7.5SA/7.5EG exhibit excellent thermodynamic properties. The results of the heat release rate (HRR), total heat release (THR), total smoke production (TSP), and smoke production rate (SPR) could demonstrate the smoke-suppressant and flame-retardant of polyurethane. The system of RPUF/ADPO2/SA/EG showed excellent flame-retardant in polyurethane.

Activation and expression of endogenous CREB-regulated transcription coactivators (CRTC) 1, 2 and 3 in the rat adrenal gland.

The activation and nuclear translocation of cAMP-response element binding protein (CREB)-regulated transcription coactivator (CRTC)2 occurs in the rat adrenal gland, in response to adrenocorticotrophic hormone (ACTH) and stressors, and has been implicated in the transcriptional regulation of steroidogenic acute regulatory protein (StAR). We have recently demonstrated the activation of CRTC isoforms, CRTC1 and CRTC3, in adrenocortical cell lines. In the present study, we aimed to determine the activation and expression of the three CRTC isoforms in vivo in relation to Star transcription, under basal conditions and following a robust endotoxic stress challenge. Rat adrenal glands and blood plasma were collected following i.v. administration of either an ultradian-sized pulse of ACTH or administration of lipopolysaccharide, as well as under unstressed conditions across the 24-hour period. Plasma ACTH and corticosterone (CORT) were measured and the adrenal glands were processed for measurement of protein by western immunoblotting, RNA by a quantitative reverse transcriptase-polymerase chain reaction and association of CRTC2 and CRTC3 with the Star promoter by chromatin immunoprecipitation. An increase in nuclear localisation of CRTC2 and CRTC3 followed increases in both ultradian and endotoxic stress-induced plasma ACTH, and this was associated with increased CREB phosphorylation and corresponding increases in Star transcription. Both CRTC2 and CRTC3 were shown to associate with the Star promoter, with the dynamics of CRTC3 binding corresponding to that of nuclear changes in protein levels. CRTC isoforms show little variation in ultradian expression or variation across 24 hours, although evidence of long-term down-regulation following endotoxic stress was found. We conclude that co-transcription factors CRTC2 and, more clearly, CRTC3 appear to act alongside phosphorylated CREB in the generation of ultradian pulses of Star transcription, essential for the maintenance of basal StAR expression. Similarly, our findings suggest CRTC2 and CRTC3 mediate Star transcriptional initiation following an endotoxic stressor; however, other transcription factors are likely to be responsible for the long-term up-regulation of adrenal Star transcription.

Successful simulation requires bridging levels of abstraction.

Although many simulations draw upon only one level of abstraction, the process for generating rich simulations requires a dynamic interplay between abstract and concrete knowledge. A complete model of simulation must account for a mind and brain that can bridge the perceptual with the conceptual, the episodic with the semantic, and the concrete with the abstract.

Prolonged treatment with the synthetic glucocorticoid methylprednisolone affects adrenal steroidogenic function and response to inflammatory stress in the rat.

Synthetic glucocorticoids are widely prescribed for the treatment of numerous inflammatory and autoimmune diseases and they can also affect the way the adrenal gland produces endogenous glucocorticoids. Indeed, patients undergoing synthetic glucocorticoid treatment can develop adrenal insufficiency, a condition characterised by reduced responsiveness of the adrenal to ACTH stimulation or stressors (e.g. surgical or inflammatory stress). To better elucidate the long-term effect of synthetic glucocorticoids treatment and withdrawal on adrenal function, we have investigated the long-term effects of prolonged treatment with methylprednisolone on HPA axis dynamics and on the adrenal steroidogenic pathway, both in basal conditions and in response to an inflammatory stress (lipopolysaccharide, LPS). We have found that 5-days treatment with methylprednisolone suppresses basal ACTH and corticosterone secretion, as well as corticosterone secretion in response to a high dose of ACTH, and down-regulates key genes in the adrenal steroidogenic pathway, including StAR, MRAP, CYP11a1 and CYP11b1. These effects were paralleled by changes in the adrenal expression of transcription factors regulating steroidogenic gene expression, as well as changes in the expression of adrenal clock genes. Importantly, 5 days after withdrawal of the treatment, ACTH levels are restored, yet basal levels of corticosterone, as well as most of the key steroidogenic genes and their regulators, remain down regulated. We also show that, although 5-days treatment with methylprednisolone reduces the corticosterone response to LPS, an increase in intra-adrenal pro-inflammatory cytokine gene expression was observed. Our data suggests that the steroidogenic pathway is directly affected by synthetic glucocorticoid treatment in the long-term, presumably via a mechanism involving activation of the glucocorticoid receptor. Furthermore, our data suggests a pro-inflammatory effect of synthetic glucocorticoids treatment in the adrenal gland.

Involvement of CREB-regulated transcription coactivators (CRTC) in transcriptional activation of steroidogenic acute regulatory protein (Star) by ACTH.

Studies in vivo have suggested the involvement of CREB-regulated transcription coactivator (CRTC)2 on ACTH-induced transcription of the key steroidogenic protein, Steroidogenic Acute Regulatory (StAR). The present study uses two ACTH-responsive adrenocortical cell lines, to examine the role of CRTC on Star transcription. Here we show that ACTH-induced Star primary transcript, or heteronuclear RNA (hnRNA), parallels rapid increases in nuclear levels of the 3 isoforms of CRTC; CRTC1, CRTC2 and CRTC3. Furthermore, ACTH promotes recruitment of CRTC2 and CRTC3 by the Star promoter and siRNA knockdown of either CRTC3 or CRTC2 attenuates the increases in ACTH-induced Star hnRNA. Using pharmacological inhibitors of PKA, MAP kinase and calcineurin, we show that the effects of ACTH on Star transcription and CRTC nuclear translocation depend predominantly on the PKA pathway. The data provides evidence that CRTC2 and CRTC3, contribute to activation of Star transcription by ACTH, and that PKA/CRTC-dependent pathways are part of the multifactorial mechanisms regulating Star transcription.

Simulating other people changes the self.

The self is not static. Our identities change considerably over development and across situations. Here, we propose one novel cause of self-change: simulating others. How could simply imagining others change the self? First, when simulating other people's mental states and traits, individuals access self-knowledge; they do so while concurrently considering information about the other person they are trying to understand. Second, episodic and semantic knowledge is malleable and susceptible to incorporating new, postevent information. If self-knowledge is similarly malleable, then simulation may change self-knowledge such that it incorporates information about the simulated person (i.e., "postevent information"). That is, simulation should render the self more similar to the simulated other. We test this hypothesis in 8 studies. In each study, participants (a) recalled personal information (e.g., traits and episodic memories), (b) simulated other people in similar contexts, and (c) re-recalled personal information. Results consistently demonstrated that simulating others changed self-knowledge, such that the self becomes more similar to the simulated other. This effect occurred for both traits and memories, spanned self-report and linguistic measures, and persisted 24 hr after simulation. The findings suggest that self-knowledge is susceptible to misinformation effects similar to those observed in other forms of semantic and episodic knowledge. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Fabrication of step-by-step drug release system both sensitive to magnetic field and temperature based on layered double hydroxides and PNIPAM.

Fabrication of environmental sensitive and controllable drug release systems is urgently needed. In this paper, thermosensitive and magnetic response drug release systems were fabricated via layer-by-layer technique using acetylsalicylic acid (AA) intercalated ZnAl-LDH as core, poly (N-isopropylacrylamide) (PNIPAM) and AA micelles as well as small size ZnAl-LDH sheets as building blocks of the shell. By forming anionic micelles, cationic PNIPAM macromolecules were sandwiched in the LDH sheets with cationic charges which provided a novel way of fabrication of drug release systems. The characteristics of the building blocks, the fabrication process and the release behaviors of the as-prepared drug release systems were characterized in detail. Due to the micro-environmental difference of AA in the core and shell of the systems, step-by-step release behaviors were observed. Also the drug release systems showed obvious temperature and magnetic field dependent responsibility. The obtained assembly is a potential drug release system.

Dynamic responses of the adrenal steroidogenic regulatory network.

The hypothalamic-pituitary-adrenal axis is a dynamic system regulating glucocorticoid hormone synthesis in the adrenal glands. Many key factors within the adrenal steroidogenic pathway have been identified and studied, but little is known about how these factors function collectively as a dynamic network of interacting components. To investigate this, we developed a mathematical model of the adrenal steroidogenic regulatory network that accounts for key regulatory processes occurring at different timescales. We used our model to predict the time evolution of steroidogenesis in response to physiological adrenocorticotropic hormone (ACTH) perturbations, ranging from basal pulses to larger stress-like stimulations (e.g., inflammatory stress). Testing these predictions experimentally in the rat, our results show that the steroidogenic regulatory network architecture is sufficient to respond to both small and large ACTH perturbations, but coupling this regulatory network with the immune pathway is necessary to explain the dissociated dynamics between ACTH and glucocorticoids observed under conditions of inflammatory stress.

Emotion regulation of fear and disgust: differential effects of reappraisal and suppression.

Although excessive fear has been central to traditional conceptualisations of the anxiety disorders, recent research suggests that disgust may also play a role in the development of some anxiety disorders. While dysregulation of emotion may confer risk for the development of anxiety disorders, it remains unclear if there are differences in the extent to which fear and disgust can be effectively regulated. To fill this important gap in the literature, unselected participants (N = 95) experienced fear or disgust via video exposure, and they were instructed to employ either reappraisal or suppression to regulate their emotional experience while viewing the videos. For those exposed to fear-relevant content, change in emotional distress did not significantly differ between those that suppressed and those that reappraised. However, significantly less emotional distress was observed for those that reappraised compared to those that suppressed when exposed to disgust-relevant content. Although physiological arousal varied over time as a function of the emotional content of the videos, it did not vary as a function of emotion regulation strategy employed. These findings suggest that reappraisal may be especially effective in regulating verbal distress when exposed to disgusting cues in the environment. The implications of these findings for the treatment of anxiety disorders that are characterised by excessive disgust reactions will be discussed.

Dynamic pituitary-adrenal interactions in response to cardiac surgery.

OBJECTIVES: To characterize the dynamics of the pituitary-adrenal interaction during the course of coronary artery bypass grafting both on and off pump. Since our data pointed to a major change in adrenal responsiveness to adrenocorticotropic hormone, we used a reverse translation approach to investigate the molecular mechanisms underlying this change in a rat model of critical illness. CLINICAL STUDIES: Prospective observational study. ANIMAL STUDIES: Controlled experimental study. CLINICAL STUDIES: Cardiac surgery operating rooms and critical care units. ANIMAL STUDIES: University research laboratory. CLINICAL STUDIES: Twenty, male patients. ANIMAL STUDIES: Adult, male Sprague-Dawley rats. CLINICAL STUDIES: Coronary artery bypass graft-both on and off pump. ANIMAL STUDIES: Injection of either lipopolysaccharide or saline (controls) via a jugular vein cannula. CLINICAL STUDIES: Blood samples were taken for 24 hours from placement of the first venous access. Cortisol and adrenocorticotropic hormone were measured every 10 and 60 minutes, respectively, and corticosteroid-binding globulin was measured at the beginning and end of the 24-hour period and at the end of operation. There was an initial rise in both levels of adrenocorticotropic hormone and cortisol to supranormal values at around the end of surgery. Adrenocorticotropic hormone levels then returned toward preoperative values. Ultradian pulsatility of both adrenocorticotropic hormone and cortisol was maintained throughout the perioperative period in all individuals. The sensitivity of the adrenal gland to adrenocorticotropic hormone increased markedly at around 8 hours after surgery maintaining very high levels of cortisol in the face of "basal" levels of adrenocorticotropic hormone. This sensitivity began to return toward preoperative values at the end of the 24-hour sampling period. ANIMAL STUDIES: Adult, male Sprague-Dawley rats were given either lipopolysaccharide or sterile saline via a jugular vein cannula. Hourly blood samples were subsequently collected for adrenocorticotropic hormone and corticosterone measurement. Rats were killed 6 hours after the injection, and the adrenal glands were collected for measurement of steroidogenic acute regulatory protein, steroidogenic factor 1, and dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 messenger RNAs and protein using real-time quantitative polymerase chain reaction and Western immunoblotting, respectively. Adrenal levels of the adrenocorticotropic hormone receptor (melanocortin type 2 receptor) messenger RNA and its accessory protein (melanocortin type 2 receptor accessory protein) were also measured by real-time quantitative polymerase chain reaction. In response to lipopolysaccharide, rats showed a pattern of adrenocorticotropic hormone and corticosterone that was similar to patients undergoing coronary artery bypass grafting. We were also able to demonstrate increased intra-adrenal corticosterone levels and an increase in steroidogenic acute regulatory protein, steroidogenic factor 1, and melanocortin type 2 receptor accessory protein messenger RNAs and steroidogenic acute regulatory protein, and a reduction in dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 and melanocortin type 2 receptor messenger RNAs, 6 hours after lipopolysaccharide injection. CONCLUSIONS: Severe inflammatory stimuli activate the hypothalamic-pituitary-adrenal axis resulting in increased steroidogenic activity in the adrenal cortex and an elevation of cortisol levels in the blood. Following coronary artery bypass grafting, there is a massive increase in both adrenocorticotropic hormone and cortisol secretion. Despite a subsequent fall of adrenocorticotropic hormone to basal levels, cortisol remains elevated and coordinated adrenocorticotropic hormone-cortisol pulsatility is maintained. This suggested that there is an increase in adrenal sensitivity to adrenocorticotropic hormone, which we confirmed in our animal model of immune activation of the hypothalamic-pituitary-adrenal axis. Using this model, we were able to show that this increased adrenal sensitivity results from changes in the regulation of both stimulatory and inhibitory intra-adrenal signaling pathways. Increased understanding of the dynamics of normal hypothalamic-pituitary-adrenal responses to major surgery will provide us with a more rational approach to glucocorticoid therapy in critically ill patients.