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Background/aims: The objectives of our study were to determine salivary α-amylase activity (stress biomarker) and its association with psychological status and quality of life (QoL), disease duration and intensity of symptoms (pain/burning) in patients with OLP., Methods: A total of 50 subjects participated in this case-control study: 30 patients with oral lichen planus (OLP); 20 control subjects. Unstimulated whole saliva (UWS) was collected between 9 and 10 am to avoid diurnal fluctuations. Psychological status was assessed using the Croatian validated version of the original Depression, Anxiety and Stress Scale (DASS-21). The impact of oral health on QoL was assessed using the Croatian version of the Oral Health Impact Profile Questionnaire (OHIP-CRO14)., Results: There was no statistically significant difference in salivary α-amylase activity between patients with OLP (N=30) and control subjects (N=20) (133813.3 vs. 166815.5 U/L, p=0.314; t-test). Depression, anxiety and stress showed no statistically significant difference between patients with OLP and control subjects (p=0.076, p=0.111, p=0.209; t-test). The patients with OLP had statistically significantly poorer QoL (total) compared to control subjects (p=0.004, t-test). There was a moderate positive correlation between symptom intensity (pain/burning) and poor QoL (total) (r=0.584, p<0.001), the OHIP-CRO14 dimension "physical pain" (r=0.661, p<0.001), "psychological impossibility" (r=0.555, p<0.01), "handicap" (r=0.546, p<0.01)., Conclusion: Although salivary α-amylase showed no statistically significant difference between patients with OLP and control subjects, the patients with OLP had poorer psychological status (three times higher scores for depression and two times higher scores for anxiety) and poorer QoL compared to the control subjects. Recognising and treating mental disorders in patients with OLP is important in order to break the "vicious circle" and achieve a better QoL in these patients., Competing Interests: The authors have no conflicts of interest to declare., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)

(Poly)phenols inhibit α-amylase by directly binding to the enzyme and/or by forming starch-polyphenol complexes. Conventional methods using starch as the substrate measure inhibition from both mechanisms, whereas the use of shorter oligosaccharides as substrates exclusively measures the direct interaction of (poly)phenols with the enzyme. In this study, using a chromatography-based method and a short oligosaccharide as the substrate, we investigated the detailed structural prerequisites for the direct inhibition of human salivary and pancreatic α-amylases by over 50 (poly)phenols from the (poly)phenol groups: flavonols, flavones, flavanones, flavan-3-ols, polymethoxyflavones, isoflavones, anthocyanidins and phenolic acids. Despite being structurally very similar (97% sequence homology), human salivary and pancreatic α-amylases were inhibited to different extents by the tested (poly)phenols. The most potent human salivary α-amylase inhibitors were luteolin and pelargonidin, while the methoxylated anthocyanidins, peonidin and petunidin, significantly blocked pancreatic enzyme activity. B-ring methoxylation of anthocyanidins increased inhibition against both human α-amylases while hydroxyl groups at C3 and B3' acted antagonistically in human salivary inhibition. C4 carbonyl reduction, or the positive charge on the flavonoid structure, was the key structural feature for human pancreatic inhibition. B-ring glycosylation did not affect salivary enzyme inhibition, but increased pancreatic enzyme inhibition when compared to its corresponding aglycone. Overall, our findings indicate that the efficacy of interaction with human α-amylase is mainly influenced by the type and placement of functional groups rather than the number of hydroxyl groups and molecular weight., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Acute physiological responses to psychosocial stressors are a potential pathway underlying racial disparities in stress-related illnesses. Uric acid (UA) is a potent antioxidant that has been linked to disparities in stress-related illnesses, and recent research has shown that UA is responsive to acute social stress. However, an examination of the relationships between the purinergic system and other commonly measured stress systems is lacking. Here, we measure and characterize associations of salivary uric acid (sUA) with markers of hypothalamic-pituitary-adrenal (HPA) axis activation, sympathetic-adreno-medullar (SAM) axis activation, and acute inflammation. A community sample of 103 African Americans (33 male, 70 female) completed the Trier Social Stress Test to induce social-evaluative threat. Passive drool collected before, during, and after the stressor task provided salivary reactivity measures of UA (sUA), cortisol, dehydroepiandrosterone sulfate (DHEAS), salivary alpha amylase (sAA - a surrogate marker of SAM activity) and C-reactive protein (sCRP). Multiple regressions revealed that total activation of cortisol, DHEAS, and sCRP were each positively associated with higher total activation of sUA. Additionally, DHEAS reactivity was positively associated with sUA reactivity. Relationships between HPA-axis markers and sUA were especially observed among younger and male participants. Overall, findings suggest potential coordination of stress systems with sUA in response to acute stress, which may further the contributions of biological stress processes to racial health disparities., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Douglas A. Granger reports a relationship with Salimetrics LLC that includes: board membership. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The objective of this study was to clarify whether there are sex-specific differences in salivary α-amylase and immunoglobulin A responses following acute endurance exercise in adolescent males and females with equivalent cardiorespiratory fitness levels. Twenty-six aerobically trained adolescent males and females with similar training status were enrolled in this study. Each individual executed a 1-h prolonged cycling exercise corresponding to a constant power output at 65% of peak oxygen uptake. Unstimulated whole salivary samples were taken with the passive drooling method at the 10-min period before and after exercise for the determination of salivary responses [α-amylase, immunoglobulin A, total protein and flow rate]. Salivary α-amylase activity, immunoglobulin A concentration and total protein concentration were significantly augmented immediately after acute endurance exercise. Regarding sex differences, only the salivary flow rate was significantly lower in females than in males. The findings of the present study imply that adolescent males and females appear to have similar salivary responses after acute endurance exercise, as represented by salivary α-amylase activity and immunoglobulin A concentration in connection with total protein concentration and salivary flow rate, when they are matched for peak oxygen uptake relative to fat-free body mass., (© 2023 The Authors. European Journal of Oral Sciences published by John Wiley & Sons Ltd on behalf of Scandinavian Division of the International Association for Dental Research.)

Salivary alpha amylase (sAA) is a common measure of stress reactivity, primarily reflecting sympathetic nervous system activity. Salivary cortisol is also a reliable, frequently used biomarker of stress and reflects the hypothalamic-pituitary-adrenal (HPA) axis response. This study examined heritability across varying metrics of sAA in response to a social evaluative stressor, the Trier Social Stress Test (TSST). The goal of this study was to estimate genetic and environmental influences on measurements of sAA stress reactivity. Moreover, we evaluated the shared genetic covariation between sAA and cortisol. Participants included twins aged 15-20 years (54% female). We measured alpha amylase and cortisol reactivity to the TSST via serial salivary cortisol samples collected pre- and post-TSST. Modest to moderate heritability estimates (11-64%) were observed across measures purported to capture alpha amylase stress reactivity (peak, area under the curve, baseline-to-peak change). Findings also indicate that sAA baseline and peak are primarily influenced by a shared genetic factor. There was no evidence of shared genetic influences between sAA and cortisol. These findings suggest the genetic control of the HPA and Sympathetic Adreno-Medullar axis are genetically independent of one another despite both playing a role in response to stressors., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Compared to the in-person Trier Social Stress Test (TSST), virtual reality (VR) variants reduce resource-intensity and improve standardization but induce stress with smaller effect sizes. However, higher cortisol reactivity is given for more immersive TSST-VRs. Immersivity depends on the VR-system, but perceived immersion may be targeted by exposure to, or interaction with the VR. We investigated whether stress reactivity towards the openly accessible OpenTSST VR can be enhanced by prior exposure to a sensorimotor game completed in VR as mediated by increased immersion. Therefore, N  = 58 healthy participants underwent the OpenTSST VR or its inbuilt control condition (placebo TSST-VR, pTSST-VR). Beforehand, participants completed a sensorimotor game either in VR or in real life. Stress was measured by means of self-reports, salivary cortisol concentrations, and salivary alpha-amylase (sAA) activity. Perceived immersion was assessed with the Igroup Presence Questionnaire (IPQ). The TSST-VR-group showed higher subjective stress than the pTSST-VR-group. Even though area under the curve measures indicated significant differences in cortisol levels between TSST-VR and pTSST-VR, this effect was not replicated in omnibus-analyses. Likewise, sAA was not responsive to stress. Our data suggests the OpenTSST VR does not reliably trigger physiological stress reactivity. Likewise, participants playing the VR-game before exposure to the TSST-VR did not show enhanced stress reactivity. Importantly, playing the VR-game did not lead to increased immersion (indicated by the IPQ), either. The key question resulting from our study is which manipulation may be fruitful to obtain a comparable stress response toward the TSST-VR compared to the in-person TSST.

Virtual reality based physical stress (VRPS) paradigms could eliminate the influence of social factors on participants, and it may be a desirable tool to explore the impact of personality traits on stress levels. In this study, we attempt to explore the effects of VRPS on stress response among individuals with different personality traits. Forty male participants with an average age of 22.79 ± 0.41 years were divided into two groups based on Harm Avoidance (HA) scores of Tridimensional Personality Questionnaire (TPQ), referred to as the Low-HA group and the High-HA group. The stress levels of the participants were assessed using salivary α-amylase (sAA) activity and heart rate variability (HRV) indices pre- and post-stress. The influence of personality traits on stress response among different groups was analyzed. VRPS significantly affected the sAA activity and HRV indicators of both groups. During and after stress, there were significant differences in sAA activity and HRV indicators between the two groups. The sAA levels and HRV indices of the Low-HA group were lower than those of the High-HA group. Furthermore, sAA levels and HRV indices were correlated with the scores of TPQ. VRPS scenarios elicit different stress responses on individuals with different harm avoidance personality traits. Stress evaluation based on VR scenarios presents potential in personality trait assessments, particularly for distinguishing between individuals with low and high HA tendencies.

Objective: To establish the possible relation between total caries (TC) and caries severity (CS) with the AMY1 gene copy number (AMY1GCN)., Materials and Methods: This was an observational, cross-sectional, population-based, and association study with 303 participants. Each participant underwent a complete anamnesis and stomatological check-up, and peripheral blood was obtained to extract gDNA. TC and CS were determined as the number of caries at the dental exploration and the number of dental surfaces affected by caries, respectively, and AMY1GCN was determined by qPCR., Results: We found an elevated caries prevalence (92.7%); TC and CS were 8 ± 10 and 10 ± 13 (median ± IR). There were higher TC and CS in those participants with AMY1GCN above the mean value (0.02 and 0.01 p values, respectively). A positive correlation between TC and CS with AMY1GCN (0.11 and 0.125 r values, 0.03 and 0.01 p values, respectively) was found, in addition to an association between TC and CS with AMY1GCN (1.5 and 1.6 OR values, 0.48 and 0.26 p values, respectively)., Conclusion: TC and CS were positively related to the AMY1GCN., Clinical Relevance: Dental caries has a high prevalence and a multifactorial etiology and has been related to a genetic component. Indeed, the salivary enzyme alpha-amylase could play a significant role in caries susceptibility, considering that its codifying gene (AMY1) can show variation in its gene copy number. This can be considered an important factor for the development of caries at a genetic level., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Quantitation of salivary alpha-amylase (sAA) plays a significant role in not only theoretical studies but also clinical practice. This study reports a quantitative point-of-care testing (POCT) system for sAA quantitation anywhere, anytime and by anyone, which consists of customized electrodes and a smartphone-controlled electrochemical analyzer. Organic-inorganic hybrid nanoflowers (NFs) encapsulating α-glucosidase (AG) and glucose dehydrogenase (GDH) have been synthesized and modified onto screen-printed electrodes (SPCEs) to fabricate the customized electrodes. The SPCEs integrated with the smartphone-controlled electrochemical analyzer exhibit good analytical performance for sAA with a low detection limit of 5.02 U mL -1 and a wide dynamic range of 100-2000 U mL -1 using chronoamperometry. The reported POCT system has been successfully demonstrated for quantitation of sAA in clinical saliva samples, and the quantitation results correlated well with those of the Bernfeld method which is extensively used in clinics. More importantly, this study reveals the great potential of sAA as an early warning indicator of abnormal glucose metabolism in obese individuals. Considering the non-invasive saliva sampling process as well as the easy-to-use and cost-effectiveness features of this quantitative POCT system, quantitation of salivary sAA at home by laypersons might become an appealing choice for obese individuals to monitor their glucose metabolism status anytime.

Numerous vital signs are reported in association with stress response assessment, but their application varies widely. This work provides an overview over methods for stress induction and strain assessment, and presents a multimodal experimental study to identify the most important vital signs for effective assessment of the response to acute mental stress. We induced acute mental stress in 65 healthy participants with the Mannheim Multicomponent Stress Test and acquired self-assessment measures (Likert scale, Self-Assessment Manikin), salivary α-amylase and cortisol concentrations as well as 60 vital signs from biosignals, such as heart rate variability parameters, QT variability parameters, skin conductance level, and breath rate. By means of statistical testing and a self-optimizing logistic regression, we identified the most important biosignal vital signs. Fifteen biosignal vital signs related to ventricular repolarization variability, blood pressure, skin conductance, and respiration showed significant results. The logistic regression converged with QT variability index, left ventricular work index, earlobe pulse arrival time, skin conductance level, rise time and number of skin conductance responses, breath rate, and breath rate variability (F1 = 0.82). Self-assessment measures indicated successful stress induction. α-amylase and cortisol showed effect sizes of -0.78 and 0.55, respectively. In summary, the hypothalamic-pituitary-adrenocortical axis and sympathetic nervous system were successfully activated. Our findings facilitate a coherent and integrative understanding of the assessment of the stress response and help to align applications and future research concerning acute mental stress., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ernst et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In the course of digitalization, new stressors are emerging. In modern working and living environments, two ubiquitous, technology-mediated stressors are multitasking demands and work interruptions. However, biological stress response patterns to multitasking and work interruptions have been sparsely investigated so far. We thus aimed to comprehensively assess biological stress response patterns to both stressors and, additionally, test whether responses differ between digital and partially non-digital settings. A controlled experimental set-up was established and humans' biological markers of the Sympathetic Nervous System (SNS), the hypothalamic-pituitary adrenal (HPA) axis, and the immune system were assessed. N = 186 healthy participants (mean age: 23.2 ± 4.3 years, 74.7% female, body mass-index: 22.3 ± 3.1 kg/m 2 ) took part in this pre-registered study. Each participant was randomly assigned to one of 6 experimental conditions (1 digital single-task, 3 dual-tasks [2 parallel tasks and 1 interruption], 1 multitasking, and 1 passive, control condition). Each one of the dual-tasking as well as the multitasking conditions included a non-digital sub-task, i.e., performing a task in presence of an examiner. All other conditions involved digital tasks only. Salivary alpha-amylase (sAA) levels as a marker for SNS reactivity significantly changed in work interruptions, parallel dual-tasking, and multitasking conditions. No changes were found for control conditions. Furthermore, no significant changes over time and no differences between the conditions were identified for three biological markers: cortisol as marker for HPA axis activity as well as for two immune system markers (secretory Immunoglobulin-A, C-reactive protein). A time course similar to sAA was found for perceived stress: with increases during task execution and decreases afterwards in multitasking and parallel dual-tasking. Yet, it did not change for the work interruption, passive control, and single-tasking condition. Overall, our findings show that dual- and multitasking are perceived as stressful and are associated with an activation of the SNS, but not with responses of HPA axis or immune system. This was consistent for digital as well as partially digital task demands. Our findings will also inform future research into the differential stress effects of digital and non-digital tasks to advance our understanding of biological stress response-patterns to multitasking and work interruptions. Therefore, our findings are highly relevant for understanding the long-term biological health effects of stress in modern (digitalized) environments., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Dysregulations of the hypothalamic-pituitary-adrenal (HPA) and sympatho-adrenal medullary (SAM) axis are associated with mental and somatic illness. However, there is lack of knowledge regarding the molecular mechanisms underlying these effects. Epigenetic states in the serotonin transporter gene (SLC6A4) were shown to be associated with stress in various forms. We hypothesized that levels of DNA methylation (DNAm) of SLC6A4 would be associated with altered SAM- and HPA regulation in daily life. N = 74 healthy persons participated in the study. An ecological momentary assessment (EMA) approach was used to assess indicators of stress in daily life. Each day included six concurrent assessments of saliva, to quantify cortisol (sCort; HPA axis) and alpha-amylase (sAA; SAM axis), and to assess self-reports on subjective stress. To assess SLC6A4 DNAm, peripheral blood was drawn and analyzed via bisulfite pyrosequencing. All data were assessed in two waves three months apart, each including two days of EMA and the assessment of SLC6A4 DNAm. Data were analyzed using multilevel models. On the between-person level, higher average levels of SLC6A4 DNAm were associated with higher average levels of sAA, but not with average levels of sCort. On the within-person level, higher levels of SLC6A4 DNAm were associated with lower levels of sAA and sCort. There were no associations of subjective stress with SLC6A4 DNAm. The results help to clarify the association between environmental stress and stress axes regulation, pointing towards an important role of differential within- and between-person effects of SLC6A4 DNAm, which might shape this association., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Worldwide, Mexico is one of the countries with the highest rate of obesity, which is a condition considered the main risk factor for type 2 diabetes. Among the mechanisms that predispose to obesity, the interaction between food intake and genetic components has been little explored. Recently we evidenced a significant association between the copy number (CN) of AMY1A and AMY2A genes, the enzymatic activity of salivary and pancreatic amylase, and the frequency of childhood obesity in Mexico, a particular population due to the high consumption of starch in the diet and the high prevalence of obesity in children and adults. This review aims to find a better understanding of the role of amylase in obesity through a description of the evolution of the CN of its genes, the association of its enzymatic activity with obesity, and the effect of its interaction with starch intake on Mexican children. In addition, it denotes the importance of the experimental perspectives of further investigation regarding the mechanism by which amylase could regulate the abundance of oligosaccharide-fermenting bacteria and producers of short-chain fatty acids and/or branched-chain amino acids that could contribute to the alteration of the physiological processes associated with intestinal inflammation and metabolic deregulation that predispose to the development of obesity., (© 2023 Revista Médica del Instituto Mexicano del Seguro Social.)

Background: Sleep is fundamental to a healthy life, and sleep disorders are an important health issue in healthcare. Whole-body warm water bathing is a non-pharmacological, safe (non-invasive), and widely used method for comforting. Here, we explored the feasibility and preliminary effectiveness of sodium bicarbonate bath (SBB) on sleep quality., Methods: Healthy adults without sleep disturbances were randomly assigned to shower baths (SHB), tap-water baths (TWB, placebo tablets), or SBB. All participants took a bath (shower, tap-water, or SBB) once a day for 10 min, after dinner, for 7 days. Sleepscan-derived sleep parameters, including total sleep time (TST), symptom questionnaires, and salivary α-amylase concentration were evaluated as outcome measures., Results: Forty participants were enrolled (14, 13, and 13 in SHB, TWB, and SBB groups, respectively) and 38 participants completed the trial (13, 12, and 13, respectively). The recruitment, adherence, and completion rates were 90.9% (40/44), 95.0% (38/40), and 95.0% (38/40), respectively. The SBB group showed a significant increase (12.35 [mean]±10.07 [standard deviation] min) in the mean TST at 1-week post-intervention (p = 0.0041) than the SHB (-1.81 ± 14.58 min; p = 0.0231) and TWB (4.54 ± 10.97 min; p = 0.0377) groups. The TST scores at 1-week post-intervention, sleep onset latency, wake after sleep onset, and sleep efficiency were significantly different between the groups. Sleep satisfaction by questionnaire was significantly improved with intervention in the SBB group than that in the SHB and TWB groups. Salivary α-amylase levels significantly improved in the SBB and TWB groups than in the SHB group, with the change being greater in the SBB group., Conclusions: SBB for 7 days had positive effects that improved sleep quality of adults. Further studies are needed to examine the efficacy and safety of SBB for prolonged usage in people diagnosed with insomnia, using objective sleep measurements, and to investigate potential sleep-enhancing mechanisms of action., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Salivary amylase, encoded by the AMY1 gene, initiate the digestion of starch. Whether starch intake or AMY1 copy number is related to disease risk is currently rather unknown. The aim was to investigate the association between starch intake and AMY1 copy number and risk of cardiovascular disease (CVD) and mortality and whether there is an interaction. In addition, we aim to identify CVD-related plasma proteins associated with starch intake and AMY1 copy number., Methods: This prospective cohort study used data from 21,268 participants from the Malmö Diet and Cancer Study. Dietary data were collected through a modified diet history method and incident CVD and mortality were ascertained through registers. AMY1 gene copy number was determined by droplet digital polymerase chain reaction, a risk score of 10 genetic variants in AMY1 was measured, and a total of 88 selected CVD-related proteins were measured. Cox proportional hazards regression was used to analyze the associations of starch intake and AMY1 copy number with disease risk. Linear regression was used to identify plasma proteins associated with starch intake and AMY1 copy number., Results: Over a median of 23 years' follow-up, 4443 individuals developed CVD event and 8125 died. After adjusting for potential confounders, a U-shape association between starch intake and risk of CVD (P-nonlinearity = 0.001) and all-cause mortality (P-nonlinearity = 0.03) was observed. No significant association was found between AMY1 copy number and risk of CVD and mortality, and there were no interactions between starch intake and AMY1 copy number (P interaction > 0.23). Among the 88 plasma proteins, adrenomedullin, interleukin-1 receptor antagonist protein, fatty acid-binding protein, leptin, and C-C motif chemokine 20 were associated with starch intake after adjusting for multiple testing., Conclusions: In this large prospective study among Swedish adults, a U-shaped association between starch intake and risk of CVD and all-cause mortality was found. Several plasma proteins were identified which might provide information on potential pathways for such association. AMY1 copy number was not associated with CVD risk or any of the plasma proteins, and there was no interaction between starch intake and AMY1 copy number on disease risk., (© 2023. The Author(s).)

Children who experience early life stress demonstrate changes to their stress responses, which may modulate long-term health. Childhood cancer presents significant stress during diagnosis, treatment, and survivorship. We hypothesized that children who have completed chemotherapy treatment for ALL will demonstrate altered hormone patterns in response to a stressor compared with healthy controls. Twelve pediatric ALL survivors and 12 healthy controls completed the Trier Social Stress Test. Salivary samples, heart rate, and self-report ratings of stress were collected at baseline, pretest, and posttest. Between group comparison showed baseline (interleukin [IL]-8) was significantly higher in the survivor group versus controls (survivors: 89.9, 40.1-544.9 pg ml -1 ; controls: 30.7, 5.6-241.9 pg ml -1 , p = .001) as was peak (IL-8) (survivors: 147.1, 71.6-1177.6 pg ml -1 ; controls: 75.5, 28.6-698.6 pg ml -1 ). Peak salivary alpha-amylase (sAA) concentration was significantly lower in the survivor group (survivors: 69.3, 19.4-195.5 U ml -1 ; controls: 91.2, 27.7-213.7 U ml -1 ; p = .04). Repeated measures ANOVA revealed significant main effects for time on cortisol (F (2.35, 50.81)  = 5.9, p < .01), sAA (F (1.56, 33.17)  = 6.6, p < .01), stress ratings (F (3.42, 88.14)  = 53.4, p < .001), and heart rate (F (8, 83)  = 16.8, p < .05). Significant main effects for group were observed for IL-8 (F (1, 23)  = 8.2, p < .01) and tumor necrosis factor-α (F (1, 23)  = 6.8, p < .05). Significant interaction effects for group × time were found for sAA (F (5, 106)  = 2.8, p < .05). Our results indicate that childhood ALL survivors have similar responses to stress as healthy controls, but lower sympatho-adrenal-medullary reactivity. Therefore, altered stress regulation may present a pathway modulating long-term health in this population., (© 2022 Wiley Periodicals LLC.)

Around 50% of patients with major depression do not respond to standard first-line treatments, such as psychotherapy and pharmacotherapy. At the same time, a subgroup exhibits altered functioning of stress-responsive bodily systems, such as the central locus coeruleus/sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis. Given that these systems impact arousal and cognition, it is possible that this subgroup contributes to the high rates of non-responders. Our aim was to investigate whether sympathetic and HPA axis activity modulate treatment outcomes in patients with stress-related major depression. A total of N = 74 inpatients (median age: 50, 62% male) with signs of burnout who fulfilled diagnostic criteria for major depression were recruited. Saliva samples were collected at awakening as well as 30 and 45 min later. Alpha-amylase activity and cortisol concentrations were determined before patients underwent evidence-based multimodal treatment. Non-responders were defined as patients exhibiting a &lt;50% decrease in depression on the Beck Depression Inventory. Non-responders had significantly higher post-awakening alpha-amylase activity than responders (p = .025). In addition, alpha-amylase activity increased significantly over the course of treatment (p = .004), irrespective of responder status. Post-awakening cortisol was neither a predictor nor an indicator of treatment response. If future research confirms alpha-amylase activity as a modulator of treatment response, this may indicate a subgroup of patients with major depression which may benefit from augmentative treatments, such as heart rate variability biofeedback and/or cognitive interventions targeting high arousal., Competing Interests: Declaration of competing interest GP and BH were employed at the Burnout ward of the Private Hospital Meiringen., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Dysregulations in autonomic and endocrine stress responses are linked to the emergence of psychopathology in adolescence. However, most studies fail to consider the interplay between these systems giving rise to conflicting findings and a gap in understanding adolescent stress response regulation. A multisystem framework-investigation of parasympathetic (PNS), sympathetic (SNS), and hypothalamic pituitary adrenal (HPA) axis components and their coordination-is necessary to understand individual differences in stress response coordination which contribute to stress vulnerabilities. As the first investigation to comprehensively evaluate these three systems in adolescence, the current study employed the Trier Social Stress Test in 72 typically developing adolescents (mean age = 13) to address how PNS, SNS, and HPA stress responses are coordinated in adolescence. Hypotheses tested key predictions of the Adaptive Calibration Model (ACM) of stress response coordination. PNS and SNS responses were assessed via heart rate variability (HRV) and salivary alpha amylase (sAA) respectively. HPA responses were indexed by salivary cortisol. Analyses utilized piecewise growth curve modeling to investigate these aims. Supporting the ACM theory, there was significant hierarchical coordination between the systems such that those with low HRV had higher sAA and cortisol reactivity and those with high HRV had low-to-moderate sAA and cortisol responsivity. Our novel results reveal the necessity of studying multisystem dynamics in an integrative fashion to uncover the true mechanisms of stress response and regulation during development. Additionally, our findings support the existence of characteristic stress response profiles as predicted by the ACM model., (© 2022 The Authors. Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.)

Psychological stress is considered to be a potential contributor in the development of arterial stiffness. However, an independent association between arterial stiffness and biological markers of stress has not yet been established. We examined the independent association between salivary alpha-amylase (sAA) activity and arterial stiffness, not mediated by cardiometabolic disease associated with arterial stiffness, in a sample of healthy Japanese men and women. Participants (992 in total, 296 men and 696 women aged 30-79 years) had neither previous cardiovascular events or stroke, nor coexisting hypertension, diabetes, or dyslipidemia. Arterial stiffness was measured by the cardio-ankle vascular index (CAVI), and increased CAVI was defined as a CAVI value of 9 or higher. A saliva sample was collected in the morning and sAA was measured with a commercial assay kit. Higher sAA activity was positively associated with greater arterial stiffness particularly among women (β = 0.070; 95% CI = 0.014-0.126; p = 0.01), and not across all participants (β = 0.042; 95% CI = -0.005-0.089; p = 0.08) and in men (β = -0.005; 95% CI = -0.097-0.087; p = 0.91). The association was strongest in the group of women aged 60 years and older (β = 0.121; 95% CI = 0.018-0.224; p = 0.02). Although the association between sAA and increased CAVI (CAVI ≥ 9) was not significant in all and sex subgroups, odds ratios (OR) for CAVI ≥ 7 were significantly high in all participants (OR = 1.25; 95% CI = 1.03-1.53) and women (OR = 1.43; 95% CI = 1.12-1.82). Elevation of sAA was associated with an increase in arterial stiffness, particularly for women aged 60 years or older., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Starch-guest inclusion complexes (ICs) are a novel, clean-label flavor encapsulation system with the potential to improve stability of aroma volatiles. While amylase has been shown to modulate guest release in vitro, release by sensory perception has not been evaluated. Here, Temporal Check-All-That-Apply (TCATA) and CATA were used to compare flavor perception of starch-limonene ICs to uncomplexed limonene, and the differences in perception were explored as a function of participant salivary α-amylase activity (sAA) and salivary flow rate (sFR). High sFR levels decreased limonene perception while high sAA increased limonene perception, highlighting the potential influence of these physiological factors on flavor perception of foods. Temporal flavor perception of a chewing gum containing starch-limonene ICs and a second chewing gum containing uncomplexed limonene and corn starch (CTL) was evaluated by 99 untrained consumers who assessed taste, texture, and aroma attributes over 17 min by TCATA and CATA. In addition, participants were segmented into three clusters based on their sAA and sFR, and cluster TCATA curves for each sample and attribute were statistically compared. Overall, participants rated Citrus, Sour and Bitter (p < 0.05) significantly higher for the IC sample and rated Sweet higher for the CTL. For Citrus, Sour, and Bitter, significant differences were observed between the three clusters for the IC chewing gum, while the CTL gum showed no significant differences for these three attributes. We demonstrate that flavor perception of starch-guest ICs varies with participants' salivary α-amylase activity and flow rate. Additionally, TCATA and CATA were found to be well suited to characterize flavor release systems over a long period of time as multiple flavor percepts can be simultaneously tracked., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Although transcutaneous auricular vagus nerve stimulation (taVNS) is thought to increase central noradrenergic activity, findings supporting such mechanism are scarce and inconsistent. This study aimed to investigate whether taVNS modulates indirect markers of phasic and tonic noradrenergic activity. Sixty-six healthy participants performed a novelty auditory oddball task twice on separate days: once while receiving taVNS (left cymba concha), once during sham (left earlobe) stimulation. To maximize potential effects, the stimulation was delivered continuously (frequency: 25 Hz; width: 250 μs) at an intensity individually calibrated to the maximal level below pain threshold. The stimulation was administered 10 min before the oddball task and maintained throughout the session. Event-related pupil dilation (ERPD) to target stimuli and pre-stimulus baseline pupil size were assessed during the oddball task as markers of phasic and tonic noradrenergic activity, respectively. Prior to and at the end of stimulation, tonic pupil size at rest, cortisol, and salivary alpha-amylase were assessed as markers of tonic noradrenergic activity. Finally, we explored the effect of taVNS on cardiac vagal activity, respiratory rate, and salivary flow rate. Results showed a greater ERPD to both target and novelty compared to standard stimuli in the oddball task. In contrast to our hypotheses, taVNS did not impact any of the tested markers. Our findings strongly suggest that continuous stimulation of the cymba concha with the tested stimulation parameters is ineffective to increase noradrenergic activity via a vagal pathway., (© 2021 Society for Psychophysiological Research.)

The relationship between salivary α-amylase activity (ssAAa) and the risk of metabolic disorders remains equivocal. We aimed to assess this relationship in adults from Qatar, where obesity and type 2 diabetes are highly prevalent. We cross-sectionally quantified ssAAa in saliva and estimated AMY1 CN from whole-genome sequencing data from 1499 participants. Linear regression was used to assess the relationship between ssAAa and adiposity and glycemic markers. Logistic regression was used to examine the association between ssAAa and occurrence of obesity or diabetes. The mean and median ssAAa were significantly lower in obese individuals. There were significant inverse associations between ssAAa and BMI, and fat mass. We detected a marked effect of ssAAa on reduced odds of obesity after adjusting for age and sex, glucose, LDL, HLD, total cholesterol, and systolic and diastolic blood pressure (OR per ssAAa unit 0.998 [95% CI 0.996-0.999], p = 0.005), with ssAAa ranging between 6.8 and 422U/mL. The obesity odds were significantly lower in the upper half of the ssAAa distributional (OR 0.58 [95% CI 0.42-0.76], p<0.001) and lower in the top versus the bottom decile of the ssAAa distribution (OR 0.46 [95% CI 0.23-0.92], p = 0.03). Our findings suggest a potential beneficial relationship between high sAAa in saliva and low odds of obesity in Qatari adults., Competing Interests: The authors have no conflict of interest to declare.

Breads of higher density exhibit lower glycaemic index (GI) both in vivo and in vitro , a phenomenon generally attributed to a slower intestinal starch digestion. The aim of this work was to gain a better understanding of the relationship between bread density, oral and gastric digestion, and GI. Three breads were studied: industrial-style and traditional-style French baguettes (similar composition, different densities), and whole-wheat baguette. In vitro GI predictions confirmed that, for an identical composition, higher bread density was associated with a lower GI. Subsequent oro-gastric digestions, using the dynamic system DIDGI®, showed extensive starch digestion at the gastric stage by salivary α-amylase, in line with recently published data. They further showed that higher bread density led to a lower hydrolysis rate. The concurrence of these results with those of in vivo studies, suggests a mediating role for gastric digestion in the relationship between bread density and GI, possibly via the repercussions on the starch proportion that remains to be hydrolysed in the small intestine. This study therefore adds to the scientific knowledge of the importance of salivary α-amylase to starch digestion, and draws special attention to the possible role of the gastric phase in determining the GI.

Individuals regularly face stress, and the manner in which they cope with that stress is a crucial component in predicting stress recovery. While many engage in self-rewarding behaviors to feel better, these behaviors can come with a cost. The current study tested the effect of engaging in a different behavior after experiencing stress-prosocial behavior. Given the health benefits associated with giving to others, it is plausible that engaging in prosocial behavior is more successful in reducing the psychological and physiological responses to stress. To test this, participants underwent the Trier Social Stress Test and then either sent a gift card to a person of their choosing, received a gift card for themselves, or selected the more aesthetically pleasing gift card. Measures of self-reported mood, heart rate, blood pressure, salivary alpha-amylase, and cortisol were collected throughout the session. While the manipulation did not elicit differences in psychological or hormonal measures, the giving group showed a significantly greater downregulation of their heart rate, diastolic blood pressure, and mean arterial pressure while recovering from the stressor. Additionally, those in the giving group who evidenced greater prosocial sentiment showed a larger reduction in diastolic blood pressure and mean arterial pressure. A follow-up study suggested that these behaviors may be engaging different reward components, as those who gave a gift card reported greater "liking" while those who received a gift card reported greater "wanting". Overall, the findings show that engaging in prosocial behavior following a stressor can help to downregulate physiological stress responses., (© 2021 Society for Psychophysiological Research.)

Background: The fine-tuning of the endogenous stress response system, which includes the hypothalamus-pituitary-adrenal axis and the sympathetic nervous system (SNS), is influenced by early attachment relationships. A higher prevalence of insecure attachment has been detected in people with eating disorders (EDs). Thus, we investigated the emotional and the SNS reactivity to the Trier Social Stress Test (TSST) in women with EDs in relation to their attachment profiles., Methods: Fifty women with EDs and 20 healthy women participated into an experimental study. Attachment was evaluated by Experience in Close Relationship questionnaire. Salivary α-amylase (sAA) levels were measured to assess the SNS reactivity to TSST while the emotional response was measured by the STAI state scale., Results: Compared to women with EDs and low attachment anxiety and healthy controls, women with EDs and high attachment anxiety showed lower TSST-induced sAA production without difference in anxiety scores. Women with EDs and high attachment avoidance showed similar sAA response to TSST but higher levels of anxiety scores compared to those with low attachment avoidance and healthy controls., Conclusions: Our findings corroborate the idea that adult attachment may be associated with variability in emotional and biological responses to a psychosocial stressor in women with EDs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Esophageal carcinoma (EC) ranks sixth among cancers in mortality worldwide and effective drugs to reduce EC incidence and mortality are lacking. To explore potential anti-esophageal cancer drugs, we conducted drug screening and discovered that verdinexor, a selective inhibitor of nuclear exportin 1 (XPO1/CRM1), has anti-esophageal cancer effects both in vivo and in vitro . However, the mechanism and role of verdinexor in esophageal cancer remain unknown. In the present study, we observed that verdinexor inhibited the proliferation and migration of EC cells in vitro and suppressed tumor growth in vivo . Additionally, we found that verdinexor induced cleavage of PARP and downregulated XPO1, c-Myc, and FOSL1 expression. RNA-sequence analysis and protein-protein interaction (PPI) analysis revealed that verdinexor regulated the XPO1/c-Myc/FOSL1 axis. The results of immunoprecipitation and proximity ligation assays confirmed that verdinexor disrupted the interaction between XPO1 and c-Myc. Overexpression of c-Myc rescued the inhibition of cell proliferation and cell migration caused by verdinexor. Overexpressed FOSL1 restored the inhibited migration by verdinexor. Taken together, verdinexor inhibited cell proliferation and migration of esophageal cancer via XPO1/c-Myc/FOSL1 axis. Our findings provide a new option for the development of anti-esophageal cancer drugs., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

A large body of literature has shown the effectiveness of mindfulness-based interventions (MBI) on stress-reduction. However, little is known about their effects on psychobiological stress-markers in daily life through an ecological momentary assessment approach. Our study examines the effects of MBI on state mindfulness, perceived stress, and indicators of sympathetic-nervous-system (saliva alpha-amylase, sAA) and hypothalamic-pituitary-adrenal-axis (saliva cortisol, sCort) activation in daily life. Twenty-eight individuals participated in a three-month MBI (IG) and were compared to 46 controls (CG). An ecological momentary assessment (EMA) was used to assess mindfulness, stress, sAA and sCort at six measurements per day on two days each before and after the MBI. Multilevel-modeling was used to analyze the data on a moment-to-moment and averaged day-level. The IG showed decreased sAA levels (AUCg) from pre to post, while the CG showed increases. Furthermore, diurnal decreases in sCort (AUCi) were pronounced in the IG compared to the CG. On a momentary basis, mindfulness was associated with lower stress and sAA levels, but not sCort. As such, we show that MBI can reduce sympathetic and to a lesser extent hypothalamic-pituitary-adrenal activation in daily life. Increased mindfulness can momentarily decrease stress and stress-related autonomic activation with implications for health. Our results emphasize the importance of brief interventions that can be easily integrated into everyday life., (© 2021 The Authors. Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.)

Purpose: To investigate and compare the salivary alpha-amylase (sAA) activity as an indicator of the sympathetic activity and stress response in patients with central serous chorioretinopathy (CSC) and healthy control subjects., Methods: Prospective multicenter case series, including 80 CSC patients and 88 healthy control subjects. Central serous chorioretinopathy status was classified as either active or inactive, depending on the presence of subretinal fluid on optical coherence tomography. Salivary samples were collected in the morning from patients and control subjects of the main cohort and at midnight for the additional cohort. Salivary alpha-amylase activity was determined in all patients and control subjects., Results: Morning sAA activity was significantly higher in patients with active CSC compared with inactive CSC (P = 0.049) and to healthy control subjects (P = 0.012). There was no significant difference in sAA activity between patients with inactive CSC and control subjects (P = 1.0). Nocturnal sAA activity did not show any significant difference between patients with active CSC and either inactive CSC or control subjects (P = 0.139)., Conclusion: Morning sAA activity is increased in patients with active CSC, although diurnal rhythmicity is preserved. Measurement of sAA is easy to perform and might be an eligible tool to further investigate the relation between stress and CSC.

Purpose: An abnormality in choroidal vasculature is a known factor in the pathogenesis of central serous chorioretinopathy (CSC), a chorioretinal disease affecting mostly middle-aged males. The purpose of the present study was to investigate the role of the autonomic nervous system (ANS) in the pathophysiology of CSC., Methods: This was a cross-sectional observational study in which characteristic choroidal vasculature metrics were assessed by measuring the subfoveal choroidal thickness (FCT) and the choroidal vascularity index (CVI) using the imaging technique of enhanced-depth imaging spectral-domain optical coherence tomography (EDI-SD-OCT). Furthermore, flow signal void area features were also evaluated in the study population using OCT angiography (OCTA). Diurnal patterns of salivary α-amylase (a-AMY) production, proposed as a marker of autonomic activity, were assessed in an adult male study population affected by acute naïve CSC in comparison with matched healthy controls., Results: Results include an overall higher diurnal output of salivary a-AMY production, which is in line with the phenomenon of a sympathetic "drive" playing a role in the pathophysiology of CSC, and a flattened diurnal percentage variation in α-AMY in CSC-affected subjects. Furthermore, Pearson's coefficient test revealed statistically significant correlations between salivary α-AMY diurnal percentage variation and selected choroidal imaging biomarkers (FCT, CVI, and flow signal void area). Finally, multiple linear regression analysis identified salivary α-AMY diurnal percentage production as the sole predictor of the CVI and flow signal void area in the study population., Conclusions: Autonomic nervous system dysregulation was highlighted in CSC patients.

Background: Growing evidence shows that long non-coding RNAs (lncRNAs) play significant roles in cancer development. However, the functions of most lncRNAs in human gastric cancer are still not fully understood. Here, we explored the role of a novel c-Myc-activated lncRNA, LINC01050, in gastric cancer progression., Methods: The expression of LINC01050 in the context of gastric cancer was assessed using The Cancer Genome Atlas datasets. Its functions in gastric cancer were investigated through gain- and loss-of-function experiments combined with the Cell Counting Kit-8 assays, colony-forming assays, Transwell assays, flow cytometry, Western blot analyses, and xenograft tumor and mouse metastasis models. Potential LINC01050 transcription activators were screened via bioinformatics and validated by chromatin immunoprecipitation and luciferase assays. The interaction between LINC01050 and miR-7161-3p and the targets of miR-7161-3p were predicted by bioinformatics analysis and confirmed by a luciferase assay, RNA immunoprecipitation, RNA pull-down, and rescue experiments., Results: LINC01050 was significantly up-regulated in gastric cancer, and its high expression was positively correlated with a poor prognosis. The transcription factor c-Myc was found to directly bind to the LINC01050 promoter region and activate its transcription. Furthermore, overexpression of LINC01050 was confirmed to promote gastric cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition in vitro and tumor growth in vivo. At the same time, its knockdown inhibited gastric cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition in vitro along with tumor growth and metastasis in vivo. Moreover, mechanistic investigations revealed that LINC01050 functions as a molecular sponge to absorb cytosolic miR-7161-3p, which reduces the miR-7161-3p-mediated translational repression of SPZ1, thus contributing to gastric cancer progression., Conclusions: Taken together, our results identified a novel gastric cancer-associated lncRNA, LINC01050, which is activated by c-Myc. LINC01050 may be considered a potential therapeutic target for gastric cancer., (© 2021. The Author(s).)

Chronic stress is linked to social adversity and underlies many health disparities among ethnic minorities. Cortisol and salivary alpha-amylase (sAA) reflect sensitivity to adversity and are related to health outcomes. Our aim was to understand how social adversity influences biological responses to experimental and daily stressors in a sample of low-income African American emerging adults. In the three-week study, participants completed questionnaires, the Trier Social Stress Task (TSST), and provided four salivary samples. In week 2, participants collected saliva at home immediately after waking and just before bed for three days. Results demonstrated an asymmetrical pattern between cortisol and sAA reactivity that was related to experiences with racism and interpersonal trauma. Further, daily stress was related to lower morning and higher nighttime cortisol, indicating atypical diurnal rhythm. These findings are consistent with other forms of social adversity that lead to long-term changes in the HPA axis response pattern.LAY SUMMARYAfrican American emerging adults showed divergent cortisol and sAA responses.Social adversity predicted an asymmetrical response pattern for sAA and cortisol.Atypical diurnal rhythms were found for participants reporting high daily stress.

The c-Myc oncoprotein plays a prominent role in cancer initiation, progression, and maintenance. Long noncoding RNAs (lncRNAs) are recently emerging as critical regulators of the c-Myc signaling pathway. Here, we report the lncRNA USP2-AS1 as a direct transcriptional target of c-Myc. Functionally, USP2-AS1 inhibits cellular senescence and acts as an oncogenic molecule by inducing E2F1 expression. Mechanistically, USP2-AS1 associates with the RNA-binding protein G3BP1 and facilitates the interaction of G3BP1 to E2F1 3'-untranslated region, thereby leading to the stabilization of E2F1 messenger RNA. Furthermore, USP2-AS1 is shown as a mediator of the oncogenic function of c-Myc via the regulation of E2F1. Together, these findings suggest that USP2-AS1 is a negative regulator of cellular senescence and also implicates USP2-AS1 as an important player in mediating c-Myc function., (© 2021. The Author(s).)

This study investigated whether transcutaneous auricular vagus nerve stimulation (taVNS) enhances reversal learning and augments noradrenergic biomarkers (i.e., pupil size, cortisol, and salivary alpha-amylase [sAA]). We also explored the effect of taVNS on respiratory rate and cardiac vagal activity (CVA). Seventy-one participants received stimulation of either the cymba concha (taVNS) or the earlobe (sham) of the left ear. After learning a series of cue-outcome associations, the stimulation was applied before and throughout a reversal phase in which cue-outcome associations were changed for some (reversal), but not for other (distractor) cues. Tonic pupil size, salivary cortisol, sAA, respiratory rate, and CVA were assessed at different time points. Contrary to our hypothesis, taVNS was not associated with an overall improvement in performance on the reversal task. Compared to sham, the taVNS group performed worse for distractor than reversal cues. taVNS did not increase tonic pupil size and sAA. Only post hoc analyses indicated that the cortisol decline was steeper in the sham compared to the taVNS group. Exploratory analyses showed that taVNS decreased respiratory rate but did not affect CVA. The weak and unexpected effects found in this study might relate to the lack of parameters optimization for taVNS and invite to further investigate the effect of taVNS on cortisol and respiratory rate., (© 2021 Society for Psychophysiological Research.)

Despite considerable research with adults suggesting that acute stress negatively affects working memory (WM), a core cognitive function, few studies have assessed these effects in youths. Studies that have been conducted have produced null findings, although these studies did not measure stress via multiple systems (e.g., hypothalamic-pituitary-adrenal [HPA] axis and sympathetic nervous system [SNS]) or include wide developmental age ranges. In the current study, we examined the links between acute stress and WM in 8- to 15-year-olds. Youths completed the Trier Social Stress Test-Modified, during which repeated saliva samples were collected to measure responses of the HPA axis (cortisol) and SNS (salivary alpha-amylase). Immediately afterward, youths completed the n-back task, an established measure of WM. Accuracy and false alarm (FA) scores were computed to explore whether associations between arousal and WM differed when WM versus only the inhibitory control facet of WM processes were considered. Relations varied as a function of age, physiological system, and type of WM process. Accuracy improved and FA scores deceased as age and SNS reactivity increased, particularly in combination. Moreover, when arousal was higher according to only one physiological system (HPA axis or SNS), FA scores were lower, but when arousal was driven by both systems or low in both systems, FA scores were higher. Together, results highlight the need for more complex investigations of stress and WM across development that take into account system-specific responses and multiple facets of WM., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: Stress is known to be a potential contributor to the development of diabetes and hypertension. However, the biological mechanisms underlying the association between cardiometabolic risk markers and the biological stress response have not yet been determined. Therefore, we examined salivary alpha-amylase and heart rate variability in relation to cardiometabolic status in a sample of healthy Japanese men and women., Methods: Participants (473 men and 1,029 women aged 30-84) underwent a 75 g oral glucose tolerance test after a 10-hr fast. The homeostasis model assessment index for insulin resistance was based on fasting and 2-hr postload glucose and insulin concentrations. Sitting blood pressure was measured twice after rest. A saliva sample was collected in the morning and salivary alpha-amylase was assayed. A 5-min heart rate variability recording was evaluated using time-domain indices of standard deviations of normal-to-normal intervals and root mean square of successive differences. Multivariate linear regression models were used to estimate associations between salivary alpha-amylase and each outcome measure., Results: Salivary alpha-amylase was associated with fasting glucose (β=0.008; 95% CI=0.002, 0.014), 2-hr postload glucose (β=0.023; 95% CI=0.004, 0.041), homeostasis model assessment index for insulin resistance (β=0.032; 95%CI=0.000, 0.064), systolic (β=1.603; 95% CI=0.479, 2.726) and diastolic (β=0.906; 95% CI=0.212, 1.600) blood pressures among women. These associations remained significant after further adjustment for heart rate variability measures., Conclusions: The elevation of salivary alpha-amylase may reflect a dysfunction of the sympathetic nervous system associated with cardiometabolic abnormalities in women.

Objective: This study aimed to examine the relationship between competitive anxiety, fear/anxiety of COVID-19, and autonomic and endocrine stress responses in professional football players after returning to competition during the COVID-19 pandemic., Methods: Ninety male professional football players (age: 26.33 ± 2.48 yr) volunteered to participate in this study, which included an official competition. Psychophysiological responses, including the Fear of COVID-19 Scale, the Coronavirus Anxiety Scale, and the Competitive State Anxiety Inventory-2 Revised, were collected 30 min before the competition. In addition, salivary alpha-amylase (sAA) and salivary cortisol (sCort) were collected at 8 a.m. and 15 min before the competition., Results: The main findings, based on the Pearson correlation, showed significant positive correlations between COVID-19 anxiety and somatic competitive anxiety (p = 0.01), cognitive competitive anxiety (p = 0.01), and competition response of sCort and sAA (p = 0.01). Moreover, fear of COVID-19 was positively correlated with COVID-19 anxiety (p = 0.01). On the contrary, the awakening response of sCort and sAA was not found to be correlated with psychological parameters (all p > 0.05). The analysis also indicated that there was no significant correlation between self-confidence with other psychological and physiological variables (all p > 0.05). The regression analysis showed that cognitive anxiety was a relevant predictor for the competition response of sCort and sAA (p < 0.05). Moreover, COVID-19 anxiety was the only predictor of somatic and cognitive anxiety (p < 0.05)., Conclusions: The present study provides the first preliminary evidence that COVID-19 anxiety and competitive anxiety might pose a negative impact on the athletic performance of professional football players during COVID-19 pandemic competitions. Thus, research is needed to build a strategy to reduce the psychophysiological stress related to COVID-19 and competition response., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Facial expressions contain important affective information, and selective attention to facial expression provides an advantage in the face of loss, stress and danger. In addition, the sympathetic nervous system and hypothalamus-pituitary-adrenal axis mediate the organism's response to loss and danger. Here, we aimed at investigating the influence of sympathetic nervous system and hypothalamus-pituitary-adrenal axis activation on selective attention to affective facial stimuli., Methods and Materials: One hundred-and-four healthy men between 18-35 years old (mean (standard deviation) age: 24.1 (3.5) years) participated in the study. We used a randomised, double-blind, placebo-controlled design. Participants received either: (a) yohimbine, (b) hydrocortisone, (c) yohimbine and hydrocortisone or (d) placebo only and participated in a dot-probe task with sad, happy and neutral faces. We collected salivary samples to measure cortisol and alpha amylase activity in addition to measurements of blood pressure and heart rate. Salivary cortisol served as correlate of hypothalamus-pituitary-adrenal axis activation and salivary alpha amylase activity, blood pressure and heart rate as correlates of sympathetic nervous system activation. Measurements were carried out before and after drug administration., Results: We did not find a main effect or interaction effect of hydrocortisone or yohimbine administration on selective attention to happy faces. However, we found an interaction of yohimbine and hydrocortisone on selective attention to sad faces. Post-hoc t -test revealed an attentional bias away from sad stimuli and towards neutral faces in the hydrocortisone-only group., Discussion: Only hydrocortisone administration led to an attentional bias away from sad faces. Future studies should investigate these effects in major depression disorder, as this disorder is characterised by glucocorticoid resistance and increased processing of sad stimuli.

Social withdrawal is an early and common feature of psychiatric disorders. Hypothalamic-pituitary-adrenal (HPA)-axis activation through increased salivary cortisol (sC) and sympathetic activation through increased salivary alpha-amylase (sAA) may play a role. We aimed to study whether the link between increased sC and sAA on the one hand and depression on the other hand is mediated by social withdrawal. In this cross-sectional, observational study, sC and sAA measures were measured in seven saliva samples in 843 participants (231 psychiatric patients and 612 healthy controls). Social withdrawal was assessed through the Brief Symptom Inventory (BSI)-, the Short Form 36-, and the Dutch Dimensional Assessment of Personality Pathology social withdrawal subscales, and analyzed using linear regression and mediation analyses. On average, participants were 44.0 years old (SD = 12.8; 64.1% female). Basal and diurnal sAA were unrelated to any social withdrawal scale and depression. Certain sC measures were positively associated with the BSI social withdrawal subscale (i.e., area under the curve with respect to the increase, beta = 0.082, p = 0.02; evening sC value: beta = 0.110, p = 0.003; and mean sC value: beta = 0.097; p = 0.01). We found limited support for statistical mediation by social withdrawal (measured using a composite social withdrawal score) on the relationship between evening sC and depression. Thus, although we found no support for a role of basal and diurnal sAA in social withdrawal, HPA-axis activation may partly aggravate social withdrawal in depressive disorders., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Reductions in memory practice effects have gained interest as risk factor for future cognitive decline. Practice effects vary with age and can be moderated by factors such as individual variability in arousal or stress experience acting as an additional cognitive load., Objective: In the current pilot study, we examined whether sympathetic nervous system activation moderates the relationship between age and practice effects., Methods: Thirty cognitively healthy individuals aged 40-70 years performed a mnemonic discrimination task twice. Salivary alpha amylase (sAA) samples were obtained at different time points as a proxy of sympathetic activity. Spearman correlations examined the relation between practice effects and sAA. Subsequently, age by sAA interactions on practice scores were explored with bootstrapped linear regression models. Additionally, participants were divided in learners (exhibiting practice effects) and non-learners based on the difference in mnemonic discrimination performance., Results: Higher age and baseline SNS activity were independently related to lower practice effects. The non-learners showed significantly higher sAA scores at all time points compared to learners. Among the learners, baseline-adjusted lower levels of sAA after encoding were associated with greater practice effects, particularly in middle-aged individuals. No such interaction was observed for non-learners., Conclusion: These results show that higher baseline sympathetic activation is associated with worse practice effects independently of age. Additionally, in a subgroup of middle-aged learners practice effects were observed when sympathetic activity remained low during learning. These findings suggest that elevated sympathetic nervous system activation may be a promising indicator of imminent cognitive decline.

Objective. Individual stress tests characterized by social evaluative threat and uncontrollability are known to elicit strong neuroendocrine responses. We tested whether a psychosocial stressor submitted to a larger group of participants (up to 60) may elicit comparable stress responses. Methods. A total of 59 adult subjects (33 women, 26 men) participated in the study, whereas 24 of them suffered from allergy and 35 were healthy. The stress test consisted of a distraction stress task followed by a speech task, in which the participants were randomly subjected to questions related to a topic that they had to prepare as well as arithmetic questions in front of their peers and a committee that responded in standardized and non-supporting manner. State and trait anxiety inventory (STAI) for anxiety state was administrated before and after the test and salivary samples taking. The test was repeated after five months. Results. The results showed that the shared psychosocial stress application in a larger group of subjects was prosperous. The larger group test (LGST) resulted in an enhanced subjectively experienced stress and an intensive sympathetic nervous system activation, reflected by elevated salivary alpha-amylase activity and the heart rate. The cortisol increment after exposure to the stress test was not significant. Repeated exposure to the test failed to reproduce the original stress responses with exception of the heart rate rise. Conclusions. In a larger group of subjects, the psychosocial stress test did elicit stress responses similar to the individual stress tests. Our data indicate that the above-mentioned stress test is apparently not an appropriate approach for the repeated use., (© 2020 Jakub Rajcani et al., published by Sciendo.)

For the measurement of salivary alpha-amylase (sAA) activity, saliva samples first have to be diluted. There is some evidence for instability, that is, a decline of sAA activity in diluted samples. It is not clear which factors during dilution may contribute to this phenomenon and how quickly this decline of sAA activity occurs. Several experiments were conducted to investigate whether and how the material of the container (polystyrene (PS), polypropylene (PP), glass; experiment 1) and the diluent (saline (NaCl) solution, phosphate buffer saline (PBS), ultra-pure water; experiment 2) may affect sAA stability in diluted samples over a broad time window of up to 5 h. To study the velocity of the phenomenon in a fine-grained temporal resolution, sAA activity during the dilution process was studied (experiment 3). The results suggest that the (in)stability of sAA activity in diluted samples is determined by the interaction of material, diluent, and time. The sAA activity was relatively stable if saliva samples were diluted with a NaCl solution or PBS in glass tubes. However, sAA activity in diluted samples decreased in plastic containers (PS, PP), or if ultra-pure water was used as the diluent. There was a clear time effect on this decline. However, the decline appears to require some time to evolve and may not occur immediately during the dilution process. To conclude, the dilution of saliva samples should preferably be conducted with NaCl solution or PBS in glass containers. If glass containers are not available, PS and PP containers can be used if the dilution is processed quickly (within 25 min) and the measurement is initiated immediately upon dilution., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Depression is characterized by difficulties regulating emotions, which may result from executive control impairment. For some individuals, stress exposure leads to executive control impairment. The current study examined whether executive control measured under conditions of acute stress is associated with reappraisal ability and prospectively predicts symptoms of depression during a stressful time of life. Sixty-six participants completed either a laboratory stress induction or a control task. Executive control was measured before and after the stress induction or control task. Reappraisal ability was measured by self-reported negative emotion while viewing aversive images. Participants reported depressive symptoms at baseline and during a period of life stress. Lower levels of executive control under stress were associated with reduced reappraisal ability. Lower levels of executive control under stress also prospectively predicted higher depressive symptoms. Finally, reduced reappraisal ability prospectively predicted higher depressive symptoms. Findings suggest that level of executive control when under stress may contribute to reappraisal ability and symptoms of depression during a time of life stress., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Many decisions under risk and uncertainty are made under physical or emotional stress. A recent meta-analysis suggested that stress reliably influences risk taking but did not find a relation between single measures of stress such as cortisol and risk taking. One reason for the conflicting findings could be that the influence of stress on risk taking depends not only on physiological but also on psychological stress responses, in particular affective valence. We tested this hypothesis in an exploratory empirical study: Seventy participants worked on a financial risk-taking task. In half of the participants acute stress was induced with a cold pressor task. For all participants we measured cortisol and α-amylase levels, blood pressure, subjective arousal, and affective valence before and after the task. The stress induction increased participants' levels of cortisol, subjective arousal, and systolic blood pressure but did not directly influence negative affect or risky decision making. Examining the interplay between physiological and psychological stress responses, a moderation analysis revealed an interaction between stress induction and affect valence: Negative affect predicted an increase in risk-seeking decision making in the stress condition, but not in the control group. A similar moderation was found with cortisol reactivity, that is, negative affect predicted an increase in risk-seeking decision making in participants with high cortisol reactivity but not in participants with low cortisol reactivity. These results suggest that the effect of stress on risky decision making depends on the interplay of affective valence and cortisol reactivity., (© 2020 The Authors. Psychophysiology published by Wiley Periodicals, Inc. on behalf of Society for Psychophysiological Research.)

This study aimed to evaluate the effect of types of horticultural activities among elderly individuals in a senior citizen learning camp. We arranged four horticultural activities: Grass Doll, Kokedama, Rocky Leaf Prints, and Herb Tasting and Smelling. Twenty-seven senior citizens (60 to 76 years) were recruited to participate. We assessed their physiological and mental state before and after the activities by measuring heart rate variability (HRV), pulse rate, blood pressure, salivary amylase activity (SAA), and Profile of Mood States (POMS). Results showed that SAA was significantly lower after the Rocky Leaf Prints, Herb Tasting and Smelling, and Kokedama. Pulse rate had a downward trend after the four horticultural activities. The ratio of low frequency (LF) over high frequency (HF) results showed that the Rocky Leaf Prints had a larger downward trend, followed by Herb Tasting and Smelling. POMS scores indicated significant improvement for Rocky Leaf Prints and Herb Tasting and Smelling. The types including artistic creation and food tasting were promising methods for psychological relaxation, stress reduction, and vigor enhancement for elderly persons. Findings showed that the impact of activities involving contact with plants was more significant in short-term activities. We hope this study can help plan the horticultural activities of the elderly in the future.

In recent years, research in behavioral medicine has become increasingly focused on understanding how chronic and acute exposure to stress impacts health outcomes. During stress, the body's physiological stress systems are activated. These systems closely interact with the immune system and are, thus, importantly implicated in the onset and maintenance of disease states. While much of the research in behavioral medicine that has investigated the effects of stress on disease has focused on the role of the hypothalamic-pituitary-adrenal axis and its downstream biomarker, cortisol, it is evident that the autonomic nervous system (ANS) also plays a crucial role in both the biological stress process and the manifestation and maintenance of stress-related symptoms. In recent years salivary alpha-amylase (sAA) has emerged as a valid and reliable marker of ANS activity in stress research and is therefore an important biomarker to consider in behavioral medicine. In this commentary, we will highlight research relevant for behavioral medicine that has utilized sAA measurements, both basally, and in response to stress, to examine ANS function in clinical populations. We will additionally summarize findings from studies that have examined the effects of various targeted interventions on changes in sAA levels. Through this, our aim is to present evidence that sAA can serve as a feasible biomarker of ANS (dys)function in health and disease. To this end, we will also highlight important methodological considerations for readers to keep in mind when including sAA assessments in their own studies. The overarching goal of this brief commentary is to highlight how a multidimensional approach toward physiological stress measurement can allow researchers to develop a better understanding of physical health and disease states.

Externalizing and internalizing behavior problems can have deleterious psychosocial consequences for youth. Both sympathetic nervous system (SNS) and hypothalamic-pituitary adrenal (HPA) axis activity and reactivity may contribute to behavior problems but have largely been studied separately, with inconsistent findings. Because the SNS and HPA axis interact to carry out physiological processes (e.g., responding to stressors), considering SNS and HPA axis activity jointly may elucidate disparate findings. This review discusses studies that simultaneously assessed SNS and HPA axis (re)activity and youth behavior problems using measures of salivary alpha amylase (sAA) and salivary cortisol. Multiple patterns of SNS and HPA axis coordination were associated with problem behaviors, especially when considering individual differences and youth's psychosocial context. Importantly, many study findings may be artifacts of widespread methodological differences. The reviewed studies lay the foundation for future research on neuroendocrine coordination as a contributing factor to youth problem behaviors and some recommendations for future research are discussed., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Childhood trauma is a non-specific risk factor for eating disorders (EDs). It has been suggested that this risk is exerted through trauma-induced long-lasting changes in the body stress response system. Therefore, we explored the activity of the hypothalamus-pituitary-adrenal axis and of the sympathetic nervous system in adult ED patients with or without a history of childhood trauma exposure. Salivary cortisol and alpha-amylase, a marker of the sympathetic nervous system activity, were measured at awakening and after 15, 30 and 60 min in 35 women with EDs. The Childhood Trauma Questionnaire (CTQ) was employed to assess exposure to childhood trauma and, according to the CTQ cut-off scores, 21 ED women were classified as maltreated (Mal) participants and 14 women as no-maltreated (noMal) ED participants. Compared to noMal ED women, Mal ED participants showed significantly decreased cortisol awakening response (between group difference: p = 0.0003) and morning salivary alpha-amylase secretion (between group difference: p = 0.02). Present results confirm that the cortisol awakening response of adult ED patients with childhood trauma exposure is lower than that of adult ED patients without childhood trauma experiences and show for the first time that also the morning secretion of salivary alpha-amylase is decreased in adult ED patients who have been exposed to early traumatic experiences. These results point for the first time to a dampening in the basal activity of both components of the endogenous stress response system in childhood maltreated adult ED women., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest to disclose., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Speech fluency can be impaired in stressful situations. In this study, it was investigated whether a verbal fluency task by itself, i.e. without the presence of any further stressors, induces responses of the hypothalamic-pituitary adrenal (HPA) axis and of the sympathetic nervous system (SNS). The sample consisted of n = 85 participants (68.2% female; 33.3 ± 15.2 years) who performed two consecutive verbal fluency tasks for two minutes each. The categories were either 'stress' or 'disease' and 'animals' or 'foods' which were presented in a randomized order. Three saliva samples were collected, prior to the task (t0), immediately after (t1), and ten minutes after it (t2). Salivary α-amylase and cortisol were assessed. Furthermore, blood pressure, heart rate, and ratings of actual stress perception, level of effort, and tiredness were measured. The verbal fluency task induced a HPA axis response with a maximum cortisol level at t2 which was independent of task performance. Furthermore, perceived stress and effort, as well as tiredness increased after the task. Moreover, tiredness immediately after the task was negatively correlated with task performance. No α-amylase, blood pressure, or heart rate, and therefore SNS, responses were found. Implications for the integrated specificity model are discussed. We conclude that a verbal fluency task acts like an acute stressor that induces a cortisol and a perceived stress response without the need for further (e.g., social-evaluative) stress components. Therefore, it is a less time-consuming alternative to other stress tasks that can be used in field studies with little effort., Competing Interests: The authors have declared that no competing interests exist.

The hypoglycaemic effects of two Ribes sp. i.e., anthocyanin-rich black currants (BC) were compared to green currants (GC), which are low in anthocyanins to establish which compounds are involved in the regulation of postprandial glycaemia. We determined the effect of the currants on inhibiting carbohydrate digestive enzymes (α-amylase, α-glucosidase), intestinal sugar absorption and transport across CaCo-2 cells. The digestion of these currants was modelled using in vitro gastrointestinal digestion (IVGD) to identify the metabolites present in the digested extracts by LC-MS/MS. Freeze-dried BC and IVDG extracts inhibited yeast α-glucosidase activity (P<.0001) at lower concentrations than acarbose, whereas GC and IVDG GC at the same concentrations showed no inhibition. BC and GC both showed significant inhibitory effects on salivary α-amylase (P<.0001), glucose uptake (P<.0001) and the mRNA expression of sugar transporters (P<.0001). Taken together this suggests that the anthocyanins which are high in BC have their greatest effect on postprandial hyperglycaemia by inhibiting α-glucosidase activity. Phytochemical analysis identified the phenolics in the currants and confirmed that freeze-dried BC contained higher concentrations of anthocyanins compared to GC (39.80 vs. 9.85 g/kg dry weight). Specific phenolics were also shown to inhibit salivary α-amylase, α-glucosidase, and glucose uptake. However, specific anthocyanins identified in BC which were low in GC were shown to inhibit α-glucosidase. In conclusion the anthocyanins in BC appear to regulate postprandial hyperglycaemia primarily but not solely by inhibiting α-glucosidase while other phenolics modulate salivary α-amylase, glucose uptake and sugar transporters which together could lower the associated risk of developing type-2 diabetes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

VuLTP1.1, a LTP1 from Vigna unguiculata, inhibits 78.1 % of the human salivary α-amylase (HSA) activity at 20 μM. We had performed a correlation study between VuLTP1.1 structure and HSA inhibitory activity and showed that two VuLTP1.1 regions are responsible for HSA inhibition. In one of them we had characterized the crucial importance of an Arg 39 for inhibition. In this work, we analyzed the VuLTP1.1-HSA interaction by protein-protein docking to understand the most probable interaction model and the mechanism of HSA inhibition by VuLTP1.1. The VuLTP1.1 tertiary structure quality and refinement as well as the docking assay between VuLTP1.1 and HSA were done by bioinformatic programs. HSA inhibition occurs by direct interaction of the VuLTP1.1 with the HSA causing the obstruction of the carbohydrate biding cleft with Gibbs free energy of -18.5 Kcal/mol and the dissociation constant of 2.6E -14 M. The previously identified Arg 39 of VuLTP1.1 is burrowed into the active site of the HSA and there it interacts with the Asp 300 of HSA catalytic site by a hydrogen bond. We had confirmed the importance of the Arg 39 of VuLTP1.1 for the HSA inhibition which interacts with the Asp 300 at the HSA active site. I-2, a LTP-like peptide, presents the same HSA inhibition pattern that VuLTP1.1, which indicates that the inhibition mechanism of the LTPs towards α-amylase is very similar. For the best of our knowledge, it is the first time that the HSA inhibition mechanism was understood and described for the LTP1s using VuLTP1.1 and I-2 as prototype inhibitors., (Copyright © 2019. Published by Elsevier Ltd.)