The investigation of collective stress experiences, including collective stressors and the psychophysiological reactivity of a collective to these stressors, has been widely neglected so far. Here, ...we examined public non-professional orchestra concerts as collective naturalistic, real-life stressors of psychosocial nature and the resulting psychophysiological reactivity in a collective of non-professional orchestra musicians.
The members of two non-professional music orchestras (N = 54) were accompanied during a public concert (stress condition) and a rehearsal (control condition). We repeatedly assessed heart rate, salivary cortisol, and excitement levels before, during, and after the concert/rehearsal in addition to the anticipatory cognitive stress appraisal.
We observed greater physiological reactivity to the concert compared to the rehearsal (p’s ≤.017), with higher increases in heart rate levels in anticipation of and in reaction to the concert and in cortisol levels in reaction to the concert compared to the rehearsal. Moreover, orchestra members reported greater psychological reactivity to the concert than to the rehearsal (p’s ≤.024) in terms of higher cognitive stress appraisal in anticipation and increased excitement levels before and during the concert compared to the rehearsal.
Our findings indicate that orchestra concerts by non-professional musicians constitute collective naturalistic, real-life stressors of psychosocial nature, resulting in significant psychophysiological stress responses with reactivity kinetics differing between the sympathetic-adrenal-medullary axis, the hypothalamic-pituitary-adrenal axis, and the psychological response. Potential implications and modulating factors need to be elucidated in future studies.
•Orchestra concerts induce psychophysiological stress responses in non-professional musicians.•Thus, orchestra concerts constitute collective naturalistic stressors of psychosocial nature.•The reactivity kinetics differs between SAM axis, HPA axis, and psychological responses.•Anticipatory responses to orchestra concerts comprise SAM axis and psychological responses.•Reactive responses to orchestra concerts were observed for SAM axis and HPA axis.
Abstract
Context
The renin-angiotensin-aldosterone system (RAAS) plays an important role in cardiovascular homeostasis and its dysfunction relates to negative health consequences. Acute psychosocial ...stress seems to activate the RAAS in humans, but stress kinetics and interrelations of RAAS parameters compared with a nonstress control group remain inconclusive.
Objective
We systematically investigated in a randomized placebo-controlled design stress kinetics and interrelations of the reactivity of RAAS parameters measured in plasma and saliva to standardized acute psychosocial stress induction.
Methods
58 healthy young men were assigned to either a stress or a placebo control group. The stress group underwent the Trier Social Stress Test (TSST), while the control group underwent the placebo TSST. We repeatedly assessed plasma renin, and plasma and salivary aldosterone before and up to 3 hours after stress/placebo. We simultaneously assessed salivary cortisol to validate successful stress induction and to test for interrelations.
Results
Acute psychosocial stress induced significant increases in all endocrine measures compared with placebo-stress (all P ≤ .041). Highest renin levels were observed 1 minute after stress, and highest aldosterone and cortisol levels 10 and 20 minutes after stress, with salivary aldosterone starting earlier at 1 minute after stress. Renin completed recovery at 10 minutes, cortisol at 60 minutes, salivary aldosterone at 90 minutes, and plasma aldosterone at 180 minutes after stress. Stress increase scores of all endocrine measures related to each other, as did renin and cortisol areas under the curve with respect to increase (AUCi) and salivary and plasma aldosterone AUCi (all P ≤ .047).
Conclusions
Our findings suggest that in humans acute psychosocial stress induces a differential and interrelated RAAS parameter activation pattern. Potential implications for stress-related cardiovascular risk remain to be elucidated.
The mineralocorticoid hormone aldosterone is a key regulator of the sodium–potassium balance and blood pressure. In excess, aldosterone relates to hypertension and cardiovascular disease (CVD). Here, ...we systematically investigated aldosterone secretion during the day in terms of salivary aldosterone awakening response (AldAR) and salivary aldosterone daytime levels (AldDay) under controlled conditions in participants’ natural environment including assessment of potential confounding variables.
In 40 healthy young men, saliva samples for AldAR were collected immediately after awakening and 15, 30, 45, and 60 min thereafter. AldDay levels were measured in 1 h intervals from 9:00–22:00 h. Analyses were complemented by salivary cortisol assessment. Fluid and food intake was standardized and as potential confounders, we assessed awakening time and sleep duration, age, BMI and MAP, as well as chronic stress.
Awakening was followed by significant increases in salivary aldosterone (p = .004, f= 0.31), returning to baseline levels > 60 min later. Longer sleep duration was associated with lower AldAR (p < .001, f= 0.36). Over the course of the day we observed a continuous decrease of AldDay (p < .001, f= 0.45). Longer sleep duration (p = .097, f= .21), later time of awakening (p < .001, f= .29), and higher chronic stress (p = .041, f= .23) were associated with AldDay characteristics. Circadian aldosterone secretion was positively associated with most cortisol measures.
We observed an awakening response in salivary aldosterone and could confirm a decrease in aldosterone levels during the day, comparable to cortisol. Significant confounders were sleep-related variables and chronic stress. Clinical implications of circadian aldosterone secretion with respect to CVD risk remain to be elucidated.
•Salivary aldosterone showed a response to awakening.•Salivary aldosterone levels decreased over the course of the day.•Sleep duration was associated with the salivary aldosterone awakening response.•Sleep duration, awakening time, and chronic stress related to daytime aldosterone.
DNA damage and the capacity to repair damaged DNA have been associated with the pathogenesis of several diseases such as cancer. While it is well known that external mutagenic agents can induce DNA ...damage, less is known about endogenous contributors to genomic instability. The aim of this study was to investigate whether excess body weight as a physiological factor and vital exhaustion as a psychological factor would be associated with basal levels of DNA damage as well as DNA repair capacity.
In a cross-sectional between-subject design we recruited 53 apparently healthy men within the normal to non-obese overweight range (mean BMI: 25.2 ± 0.5) who were either vitally exhausted (VE) (VE-score ≥ 10) or non-exhausted (VE-score ≤ 3). Vital exhaustion was assessed using the Maastricht Vital Exhaustion Questionnaire. We assessed DNA damage and repair in terms of strand breaks in PBMCs by means of the automated Fluorimetric Detection of Alkaline Unwinding (FADU) assay. DNA repair capacity was assessed by repeatedly measuring the amount of intact DNA up to 90 min after standardized X-irradiation of the cells.
General linear models revealed that elevated levels of basal DNA damage (β=−0.34, p=0.013, f=0.33) as well as impaired capacity to repair damaged DNA (F(1/50)=5.40, p=0.024, f=0.33) with increasing BMI, but not with vital exhaustion (p’s ≥ 0.63).
Our findings point to DNA integrity impairments with increasing BMI, already in the overweight range, and suggest impaired DNA repair as a potential underlying molecular mechanism. In contrast, the psychological factor vital exhaustion was not associated with DNA damage or DNA repair capacity.
•Already non-obese overweight (BMI<30) results in genomic instability in PBMCs of men.•Reduced DNA repair capacity might be a potential mechanism underlying the DNA damage with higher BMI.•Vital exhaustion is not associated with basal DNA damage or reduced DNA repair capacity.
Essential hypertension is a pivotal risk factor for the development of cardiovascular disease (CVD). Hypertensives exhibit greater stress-induced responses in various physiological systems considered ...to contribute to CVD progression. Whether this stress hyperreactivity extends to the adrenal hormone aldosterone has not yet been investigated in essential hypertension. Here, we investigated reactivity of plasma aldosterone to acute psychosocial stress induction in hypertensive and normotensive men. 21 hypertensive men and 25 normotensive controls underwent the standardized Trier-Social-Stress-Test (TSST). We repeatedly assessed plasma aldosterone before and up to 1 h after TSST cessation. Acute psychosocial stress induced significantly greater increases in hypertensives as compared to normotensives (F(3.60, 158.50) = 3.75; p = .008, f = 0.29). Our findings suggest stress-induced hyperreactivity of aldosterone in essential hypertension. Potential implications for stress-related cardiovascular risk remain to be elucidated.
•We found TSST-induced aldosterone increases in hypertensive and normotensive men.•Our results suggest aldosterone hyperreactivity to stress in essential hypertension.•Aldosterone reactivity differed 1 and 10 min after stress cessation between groups.
The renin-angiotensin-aldosterone system (RAAS) plays a relevant role in regulating blood pressure and thus maintaining cardiovascular homeostasis. Although it was recently shown that RAAS parameters ...are responsive to acute psychosocial stress, the psychobiological determinants of the acute stress-induced RAAS activation have not yet been investigated. In a randomized placebo-controlled design, we investigated potential psychological and physiological determinants of the RAAS response and underlying mechanisms.
Fifty-seven young healthy male participants underwent either an acute standardized psychosocial stress test or a nonstress placebo task. We measured aldosterone in plasma and saliva, as well as renin, and the stress-reactive endocrine measures adrenocorticotropic hormone (ACTH), epinephrine, and norepinephrine in plasma at rest, immediately after the task and several times up to 3 hours thereafter. Moreover, we assessed stress-reactive psychological (anticipatory cognitive stress appraisal, mood, physical discomfort) and basal demographic-physiological measures (age, body mass index, blood pressure).
Acute psychosocial stress elicited changes in all assessed endocrine (p values ≤ .028, ηp2 values ≥ 0.07) and stress-reactive psychological measures (p values ≤ .003, ηp2 values ≥ 0.15). The basal parameter body mass index, the stress-reactive endocrine parameters ACTH and norepinephrine, and the psychological parameter anticipatory stress appraisal were identified as determinants of higher RAAS parameter reactivity to acute psychosocial stress. The association between anticipatory cognitive stress appraisal and plasma RAAS measures was fully mediated by ACTH increases (p values ≤ .044, ηp2 values ≥ 0.05).
Cognitive stress appraisal processes seem to modulate RAAS stress reactivity. This points to potential clinical implications for psychoeducative therapeutical interventions targeting stress appraisal processes to reduce endocrine stress reactivity.
Sulfated peptides are plant hormones that are active at nanomolar concentrations. The sulfation at one or more tyrosine residues is catalysed by tyrosylprotein sulfotransferase (TPST), which is ...encoded by a single-copy gene. The sulfate group is provided by the co-substrate 3´-phosphoadenosine 5´-phosphosulfate (PAPS), which links synthesis of sulfated signaling peptides to sulfur metabolism. The precursor proteins share a conserved DY-motif that is implicated in specifying tyrosine sulfation. Several sulfated peptides undergo additional modification such as hydroxylation of proline and glycosylation of hydroxyproline. The modifications render the secreted signaling molecules active and stable. Several sulfated signaling peptides have been shown to be perceived by leucine-rich repeat receptor-like kinases (LRR-RLKs) but have signaling pathways that, for the most part, are yet to be elucidated. Sulfated peptide hormones regulate growth and a wide variety of developmental processes, and intricately modulate immunity to pathogens. While basic research on sulfated peptides has made steady progress, their potential in agricultural and pharmaceutical applications has yet to be explored.
Phytosulfokine (PSK) receptor signaling promotes root elongation, determines lateral root density, and maintains non-hair cell fate partially independent of TPST responsible for the activating ...sulfation of PSK.
Abstract
Tyrosine-sulfated peptides are key regulators of plant growth and development. The disulfated pentapeptide phytosulfokine (PSK) mediates growth via leucine-rich repeat receptor-like kinases, PSKR1 and PSKR2. PSK receptors (PSKRs) are part of a response module at the plasma membrane that mediates short-term growth responses, but downstream signaling of transcriptional regulation remains unexplored. In Arabidopsis, tyrosine sulfation is catalyzed by a single-copy gene (TPST; encoding tyrosylprotein sulfotransferase). We performed a microarray-based transcriptome analysis in the tpst-1 mutant background that lacks sulfated peptides to identify PSK-regulated genes and genes that are regulated by other sulfated peptides. Of the 169 PSK-regulated genes, several had functions in root growth and development, in agreement with shorter roots and a higher lateral root density in tpst-1. Further, tpst-1 roots developed higher numbers of root hairs, and PSK induced expression of WEREWOLF (WER), its paralog MYB DOMAIN PROTEIN 23 (MYB23), and At1g66800 that maintain non-hair cell fate. The tpst-1 pskr1-3 pskr2-1 mutant showed even shorter roots, and higher lateral root and root hair density than tpst-1, revealing unexpected synergistic effects of ligand and PSKR deficiencies. While residual activities may exist, overexpression of PSKR1 in the tpst-1 background induced root growth, suggesting that PSKR1 may be active in the absence of sulfated ligands.
Remote digital pathology allows healthcare systems to maintain pathology operations during public health emergencies. Existing Clinical Laboratory Improvement Amendments regulations require ...pathologists to electronically verify patient reports from a certified facility. During the 2019 pandemic of COVID-19 disease, caused by the SAR-CoV-2 virus, this requirement potentially exposes pathologists, their colleagues, and household members to the risk of becoming infected. Relaxation of government enforcement of this regulation allows pathologists to review and report pathology specimens from a remote, non-CLIA certified facility. The availability of digital pathology systems can facilitate remote microscopic diagnosis, although formal comprehensive (case-based) validation of remote digital diagnosis has not been reported. All glass slides representing routine clinical signout workload in surgical pathology subspecialties at Memorial Sloan Kettering Cancer Center were scanned on an Aperio GT450 at ×40 equivalent resolution (0.26 µm/pixel). Twelve pathologists from nine surgical pathology subspecialties remotely reviewed and reported complete pathology cases using a digital pathology system from a non-CLIA certified facility through a secure connection. Whole slide images were integrated to and launched within the laboratory information system to a custom vendor-agnostic, whole slide image viewer. Remote signouts utilized consumer-grade computers and monitors (monitor size, 13.3–42 in.; resolution, 1280 × 800–3840 × 2160 pixels) connecting to an institution clinical workstation via secure virtual private network. Pathologists subsequently reviewed all corresponding glass slides using a light microscope within the CLIA-certified department. Intraobserver concordance metrics included reporting elements of top-line diagnosis, margin status, lymphovascular and/or perineural invasion, pathology stage, and ancillary testing. The median whole slide image file size was 1.3 GB; scan time/slide averaged 90 s; and scanned tissue area averaged 612 mm2. Signout sessions included a total of 108 cases, comprised of 254 individual parts and 1196 slides. Major diagnostic equivalency was 100% between digital and glass slide diagnoses; and overall concordance was 98.8% (251/254). This study reports validation of primary diagnostic review and reporting of complete pathology cases from a remote site during a public health emergency. Our experience shows high (100%) intraobserver digital to glass slide major diagnostic concordance when reporting from a remote site. This randomized, prospective study successfully validated remote use of a digital pathology system including operational feasibility supporting remote review and reporting of pathology specimens, and evaluation of remote access performance and usability for remote signout.
Despite the initial successes of immunotherapy, there is an urgent clinical need for molecular assays that identify patients more likely to respond. Here, we report that ultrasensitive measures of ...circulating tumor DNA (ctDNA) and T-cell expansion can be used to assess responses to immune checkpoint blockade in metastatic lung cancer patients (
= 24). Patients with clinical response to therapy had a complete reduction in ctDNA levels after initiation of therapy, whereas nonresponders had no significant changes or an increase in ctDNA levels. Patients with initial response followed by acquired resistance to therapy had an initial drop followed by recrudescence in ctDNA levels. Patients without a molecular response had shorter progression-free and overall survival compared with molecular responders 5.2 vs. 14.5 and 8.4 vs. 18.7 months; HR 5.36; 95% confidence interval (CI), 1.57-18.35;
= 0.007 and HR 6.91; 95% CI, 1.37-34.97;
= 0.02, respectively, which was detected on average 8.7 weeks earlier and was more predictive of clinical benefit than CT imaging. Expansion of T cells, measured through increases of T-cell receptor productive frequencies, mirrored ctDNA reduction in response to therapy. We validated this approach in an independent cohort of patients with early-stage non-small cell lung cancer (
= 14), where the therapeutic effect was measured by pathologic assessment of residual tumor after anti-PD1 therapy. Consistent with our initial findings, early ctDNA dynamics predicted pathologic response to immune checkpoint blockade. These analyses provide an approach for rapid determination of therapeutic outcomes for patients treated with immune checkpoint inhibitors and have important implications for the development of personalized immune targeted strategies.
Rapid and sensitive detection of circulating tumor DNA dynamic changes and T-cell expansion can be used to guide immune targeted therapy for patients with lung cancer.
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