Long-acting porcine ACTH stimulated salivary cortisol reduces the overdiagnosis of adrenal insufficiency compared to serum cortisol in cirrhosis liver.

BACKGROUND: There are no reliable methods in clinical practice to diagnose adrenal insufficiency (AI) in patients with cirrhosis owing to variable cortisol-binding protein levels. This leads to unreliable results in ACTH stimulated serum cortisol test. We aimed to estimate the long-acting porcine (LA)ACTH-stimulated serum and salivary cortisol levels of patients at different stages of cirrhosis using second generation electrochemiluminescence and to determine the prevalence of true adrenal insufficiency in these patients. DESIGN, PATIENTS AND MEASUREMENTS: We included 135 noncritical patients with cirrhosis (45 each from CHILD A, B and C) and 45 healthy controls. Serum and salivary samples were collected at baseline in the morning and at 1 and 2 h after LA-ACTH injection. RESULTS: In healthy subjects, the 2.5th centile of 2 h ACTH stimulated serum and salivary cortisol were 19.8 and 0.97 µg/dL, which were used as cut-offs for defining AI based on serum and saliva respectively. The median (interquartile-range) 2-h stimulated salivary cortisol in Child A, B, C categories and controls were 1.36(1.23-2.38), 1.46(1.18-2.22), 1.72(1.2-2.2) and 2.12(1.42-2.72) µg/dL respectively. Six subjects (4.4%) were diagnosed to have AI based on stimulated salivary cortisol cut-off, whereas 39 (28.9%) cirrhosis subjects had inadequately stimulated serum cortisol. Three patients (symptomatic) required steroid replacement therapy. Hypoalbuminemia was identified as a major risk factor for the misdiagnosis of adrenal insufficiency by serum cortisol-based testing. CONCLUSIONS: Long-acting porcine ACTH stimulated salivary cortisol reduces the overdiagnosis of adrenal insufficiency compared to serum cortisol in cirrhosis liver. Stimulated salivary cortisol is a promising investigation for evaluation of adrenal function in cirrhosis and more studies are required for its further validation before clinical use.

The conundrum of differentiating Cushing's syndrome from non-neoplastic hypercortisolism: a systematic review and meta-analysis.

CONTEXT: Once hypercortisolemia is confirmed, differential diagnosis between Cushing's syndrome (CS) due to neoplastic endogenous hypercortisolism and non-neoplastic hypercortisolism (NNH, pseudo-Cushing's syndrome) is crucial. Due to worldwide corticotropin-releasing hormone (CRH) unavailability, accuracy of alternative tests to dexamethasone (Dex)-CRH, is clearly needed. OBJECTIVE: Assess the diagnostic accuracy of Dex-CRH test, desmopressin stimulation test, midnight serum cortisol (MSC), and late-night salivary cortisol (LNSC) levels to distinguish CS from NNH. METHODS: Articles through March 2022 were identified from Scopus, Web of Science, MEDLINE, EMBASE, and PubMed. All steps through the systematic review were performed independently and in duplicate and strictly adhered to the updated PRISMA-DTA checklist. DATA SYNTHESIS: A total of 24 articles (1900 patients) were included. Dex-CRH had a pooled sensitivity and specificity of 91% (95%CI 87-94%; I2 0%) and 82% (73-88%; I2 50%), desmopressin test 86% (81-90%; I2 28%) and 90% (84-94%; I2 15%), MSC 91% (85-94%; I2 66%) and 81% (70-89%; I2 71%), and LNSC 80% (67-89%; I2 57%) and 90% (84-93%; I2 21%), respectively. Summary receiver operating characteristics areas under the curve were Dex-CRH 0.949, desmopressin test 0.936, MSC 0.942, and LNSC 0.950 without visual or statistical significance. The overall risk of studies bias was moderate. CONCLUSION: Dex-CRH, the desmopressin stimulation test, and MSC have similar diagnostic accuracy, with Dex-CRH and MSC having slightly higher sensitivity, and the desmopressin test being more specific. LNSC was the least accurate, probably due to high heterogeneity, intrinsic variability, different assays, and lack of consistent reported cutoffs. When facing this challenging differential diagnosis, the results presented here should increase clinicians' confidence when deciding which test to perform.

Development of diagnostic algorithm for Cushing's syndrome: a tertiary centre experience.

PURPOSE: No consensus exists as the gold standard for Cushing's Syndrome (CS) screening. This study aimed to evaluate the diagnostic accuracy and utility of late-night salivary cortisol (LNSC) and cortisone (LNSE), overnight dexamethasone suppression test (ODST), and urinary free cortisol (UFC) in developing a screening algorithm for CS. METHODS: A retrospective, single-centre analysis on 93 adult patients referred to the Oxford Centre for Diabetes, Endocrinology, and Metabolism for CS evaluation (2017-2022). Data were analysed using binomial logistic regression and area under the receiver-operating curve (AUROC). RESULTS: Fifty-three patients were diagnosed with CS. LNSC (sensitivity 87.5%, specificity 64.9%, AUC 0.76), LNSE (sensitivity 72.4%, specificity 85.7%, AUC 0.79), and ODST (sensitivity 94.7%, specificity 52.1%; AUC 0.74) demonstrated comparable effectiveness for CS diagnosis. Their combined application increased diagnostic accuracy (AUC 0.91). UFC was not statistically significant. Pre-test clinical symptom inclusion improved screening test performance (AUC LNSC: 0.83; LNSE: 0.84; ODST: 0.82). For CD diagnosis, LNSE + LNSC (AUC 0.95) outperformed ODST. Combining these with ACTH levels < 12.6 pmol/L perfectly distinguished MACS (AUC 1.00). ODST (AUC 0.76) exhibited superior performance (sensitivity 100.0%, specificity 52.2%) in MACS detection. CONCLUSIONS: LNSC, LNSE, and ODST are robust tools for CS screening, with their combined use offering the highest diagnostic precision. LNSE, especially when used with LNSC, is highly effective for CD diagnosis, exceeding ODST accuracy. ODST is preferable for MACS identification. Integrating ACTH levels markedly improves differentiation between CD and MACS. Conversely, UFC shows limited diagnostic utility.

Unique and interactive effects of threat and deprivation on latent trait cortisol among emerging adults.

Though considerable work supports the Dimensional Model of Adversity and Psychopathology, prior research has not tested whether the dimensions-threat (e.g., abuse) and deprivation (e.g., neglect)-are uniquely related to salivary trait indicators of hypothalamic pituitary adrenal (HPA) axis activity. We examined the unique and interactive effects of threat and deprivation on latent trait cortisol (LTC)-and whether these effects were modified by co-occurring adversities. Emerging adults (n = 90; Mage = 19.36 years; 99.88% cisgender women) provided salivary cortisol samples four times a day (waking, 30 min and 45 min postwaking, bedtime) over three 3-day measurement waves over 13 weeks. Contextual life stress interviews assessed early adversity. Though the effects varied according to the conceptualization of early adversity, overall, threat-but not deprivation, nor other co-occurring adversities-was uniquely associated with the across-wave LTC. Specifically, the incidence and frequency of threat were each negatively related to the across-wave LTC. Threat severity was also associated with the across-wave LTC, but only among those with no deprivation. Finally, the effects of threat were modified by other co-occurring adversities. Findings suggest that threat has unique implications for individual differences in HPA axis activity among emerging adults, and that co-occurring adversities modify such effects.

A study of the effect of half-day climatotherapy on changes in salivary cortisol levels.

In our previous study setting, climatotherapy programme consisted of six sessions - four in the mid-mountain area and two in a flat park. For all sessions, the subjects underwent climatotherapy in the morning under slightly cool conditions. During each session, the subjects' blood pressure, pulse rate, skin temperature, blood lactate, salivary cortisol and mood profile were recorded, and meteorological data were collected at the sites. We hypothesised that exercise habits, changes in mood profile and effective temperatures during the session, and physical exertion during the climatic terrain cure would affect salivary cortisol levels. Subjects were 30 (spring) and 29 (autumn). Multiple linear regression analyses were performed to examine the determinants of the change in salivary cortisol levels. In the mountain setting, salivary cortisol was elevated, even though the sessions took place in the descending phase of the circadian salivary cortisol variation; however, the post-session cortisol increase was not significant. Increased post-session salivary cortisol was significantly associated with female gender, older age, higher BMI, lower body fat, less daily physical activity, increased blood lactate, increased 'Tension-Anxiety' and 'Depression-Dejection' moods, and decreased 'Anger-Hostility' mood. The increase in cortisol may have been due to older age, a predominance of females, and the increased blood lactate due to the mountainous terrain. In the flat park, the significant decrease in postsession salivary cortisol was related to the descending circadian phase of circadian cortisol variation and the low physical demands of the sessions.

Cognitive reserve, cortisol, and Alzheimer's disease biomarkers: A memory clinic study.

INTRODUCTION: Cognitive reserve might mitigate the risk of Alzheimer's dementia among memory clinic patients. No study has examined the potential modifying role of stress on this relation. METHODS: We examined cross-sectional associations of the cognitive reserve index (CRI; education, occupational complexity, physical and leisure activities, and social health) with cognitive performance and AD-related biomarkers among 113 memory clinic patients. The longitudinal association between CRI and cognition over a 3-year follow-up was assessed. We examined whether associations were influenced by perceived stress and five measures of diurnal salivary cortisol. RESULTS: Higher CRI scores were associated with better cognition. Adjusting for cortisol measures reduced the beneficial association of CRI on cognition. A higher CRI score was associated with better working memory in individuals with higher (favorable) cortisol AM/PM ratio, but not among individuals with low cortisol AM/PM ratio. No association was found between CRI and AD-related biomarkers. DISCUSSION: Physiological stress reduces the neurocognitive benefits of cognitive reserve among memory clinic patients. HIGHLIGHTS: Physiological stress may reduce the neurocognitive benefits accrued from cognitively stimulating and enriching life experiences (cognitive reserve [CR]) in memory clinic patients. Cortisol awakening response modified the relation between CR and P-tau181, a marker of Alzheimer's disease (AD). Effective stress management techniques for AD and related dementia prevention are warranted.

Infant massage as a stress management technique for parents of hospitalized extremely preterm infants.

Mothers of infants born extremely preterm requiring prolonged medical intervention in the Neonatal Intensive Care Unit (NICU) are at high risk of developing stress. Parent-administered infant massage is a well-established, safe intervention for preterm infants with many developmental benefits, but the published literature has mostly examined its impact on infants and parents through self-reported or observational measures of stress. The aim of this study was to measure salivary cortisol, a biomarker for stress, in extremely preterm infants and their mothers immediately pre and post parent-administered infant massage in order to detect potential changes in physiologic stress. Twenty-two mother-infant dyads completed massage education with a physical or occupational therapist. All dyads provided salivary cortisol samples via buccal swab immediately pre- and post-massage at the second session. Of mothers determined to be "cortisol responders" (15/22), salivary cortisol levels were lower after massage (pre-minus post-level: -26.47 ng/dL, [CI = -4.40, -48.53], p = .016, paired t-test). Our primary findings include a clinically significant decrease (as measured by percent change) in maternal cortisol levels immediately post parent-administered massage, indicating decreased physiological stress. Integration of infant massage into NICU clinical practice may support maternal mental health, but further powered studies are necessary to confirm findings.

Las madres de infantes nacidos extremadamente prematuros en la Unidad de Cuidado Intensivo Neonatal (NICU) se encentran bajo alto riesgo de desarrollar estrés. El masaje que una madre le da al infante es una intervención segura, bien establecida, para infantes prematuros, con muchos beneficios de desarrollo, aunque la información publicada disponible ha examinado por la mayor parte el impacto del masaje en los infantes y progenitores por medio de medidas de estrés auto reportadas o de observación. El propósito de este estudio fue medir el cortisol salival, un biomarcador de estrés, en infantes extremadamente prematuros y sus madres inmediatamente antes y después del masaje que la madre le da, para detectar posibles cambios en el estrés fisiológico. Veintidós díadas madre-infante completaron 2 sesiones educativas de masaje con un terapeuta físico u ocupacional. Todas las díadas aportaron muestras de cortisol salival por medio de hisopado bucal inmediatamente antes y después del masaje en la segunda sesión. Los niveles de cortisol en infantes no fueron suficientes para el análisis. De las madres a quienes se les determinó haber dado "respuesta de cortisol" (15/22), los niveles de cortisol salival fueron más bajos después del masaje (nivel antes menos nivel después: −26.47 ng/dL, [CI = −4.40, −48.53]. p = .016, prueba-t pareada). Entre nuestros resultados primarios se incluye una baja clínicamente significativa (tal como fue medida por el cambio porcentual) en los niveles de cortisol materno inmediatamente después del masaje. Estos resultados sugieren que el masaje dado por la madre a infantes prematuros pudiera reducir el cortisol materno, un marcador fisiológico de estrés.

Reduced neural responses to pleasant odor stimuli after acute psychological stress is associated with cortisol reactivity.

Acute stress alters olfactory perception. However, little is known about the neural processing of olfactory stimuli after acute stress exposure and the role of cortisol in such an effect. Here, we used an event-related olfactory fMRI paradigm to investigate brain responses to odors of different valence (unpleasant, pleasant, or neutral) in healthy young adults following an acute stress (Trier Social Stress Test, TSST) induction (N = 22) or a non-stressful resting condition (N = 22). We obtained the odor pleasantness, intensity, and familiarity ratings after the acute stress induction or resting condition. We also measured the participants' perceived stress and salivary cortisol at four time points during the procedure. We found a stress-related decrease in brain activation in response to the pleasant, but not to the neutral or unpleasant odor stimuli in the right piriform cortex extending to the right amygdala, the right orbitofrontal cortex, and the right insula. In addition, activation of clusters within the regions of interest were negatively associated with individual baseline-to-peak increase in salivary cortisol levels after stress. We also found increased functional connectivity between the right piriform cortex and the right insula after stress when the pleasant odor was presented. The strength of the connectivity was positively correlated with increased perceived stress levels immediately after stress exposure. These results provide novel evidence for the effects of acute stress in attenuating the neural processing of a pleasant olfactory stimulus. Together with previous findings, the effect of acute stress on human olfactory perception appears to depend on both the valence and the concentration (e.g., peri-threshold or suprathreshold levels) of odor stimuli.

Late-night salivary cortisol cut-offs for diagnosis of Cushing syndrome using second-generation electrochemiluminescence immunoassay kits.

CONTEXT: Late-night salivary cortisol (LNSC) is a simple and reliable screening test for Cushing syndrome (CS). With improved analytical performance of the current second-generation electrochemiluminescence immunoassay (ECLIA; Elecsys Cortisol-II; Roche Diagnostics), there is a need to revisit the LNSC cut-offs, especially in a South-Asian population. OBJECTIVE: To derive LNSC cut-offs for diagnosis of CS using second-generation ECLIA kits. DESIGN: Diagnostic accuracy study. METHODS: We prospectively recruited 155 controls aged 18-60 years, including, normal-weight (body mass index [BMI] < 25 kg/m2 and no hypertension or diabetes [n = 53]) and overweight/obese (BMI 25-30 kg/m2 and hypertension and/or diabetes [n = 52] or BMI ≥ 30 kg/m2 with/without comorbidities [n = 50]) participants. All participants submitted LNSC samples collected at home; overweight/obese controls additionally underwent dexamethasone suppression test to exclude CS. We also reviewed records of adults with endogenous CS (cases, n = 92) and a valid LNSC result using the same method. RESULTS: The 95th percentile for LNSC in controls was 6.76 nmol/L. The mean ± SD LNSC levels were 40.47 ± 49.63 nmol/L in cases and 3.37 ± 1.18 nmol/L in controls (p < 0.001). Receiver operating characteristic (ROC) analysis showed excellent diagnostic performance of LNSC for CS, with area under curves (AUCs) of 0.994 (cases vs. all controls) and 0.993 (cases vs. overweight/obese controls), respectively. The best diagnostic performance was achieved at cut-offs ≥6.73 nmol/L (sensitivity: 97.8%, specificity: 94.8%) and ≥7.26 nmol/L (sensitivity: 97.8%, specificity: 95.1%), respectively. CONCLUSIONS: LNSC measured using second-generation ECLIA demonstrated high diagnostic accuracy for CS. Based on this study, we propose a LNSC cutoff ≥6.73 nmol/L to diagnose CS.

Hypothalamic-pituitary-adrenal axis activity in patients with primary polydipsia compared to healthy controls.

OBJECTIVE: Primary polydipsia is characterized by excessive fluid intake which may suppress vasopressin levels. It is speculated that suppressed vasopressin levels lead to a dysregulated hypothalamic-pituitary-adrenal (HPA) axis as vasopressin co-modulates the HPA axis. However, data are contradictory. The aim of this study was to investigate markers of the HPA axis in patients with primary polydipsia compared to healthy controls. DESIGN: Exploratory analysis combining data from two different prospective observational studies. PATIENTS: We included 34 patients with primary polydipsia (68% females, median aged 29.5 years (interquartile range, IQR: 26.0, 38.8) and 20 healthy controls (55% females, median age 24.0 years [IQR: 22.0, 27.2]). MEASUREMENTS: The main outcome was difference in HPA axis activity assessed using circadian serum and salivary cortisol, 24-h urinary free cortisol and cortisol levels before and after adrenocorticotropic hormone (ACTH) stimulation; vasopressin suppression was assessed measuring fasting copeptin levels between patients with primary polydipsia and healthy controls using Wilcoxon rank-sum test. RESULTS: No difference was seen in circadian serum cortisol levels (p = .9), urinary free cortisol levels (p = .17) and serum cortisol in response to ACTH stimulation (p = .77) between groups. Circadian salivary cortisol levels were significantly lower in patients with primary polydipsia compared to healthy controls with an estimated difference of -3.7 nmol/L (95% CI: -5.5, -1.8 nmol/L, p < .001). Fasting copeptin levels were significantly lower in patients with primary polydipsia compared to healthy volunteers (p < 0.01). CONCLUSION: Our results suggest no difference in HPA axis activity between patients with primary polydipsia and healthy controls. The observed difference in salivary cortisol levels may be linked to a dilution effect in saliva rather than an altered stress axis considering the other findings.

Increased sensitivity to unpleasant odor following acute psychological stress.

Previous studies have reported increased sensitivity to malodor after acute stress in humans. However, it is unclear whether stress-related "hypersensitivity" to odors depends on odor pleasantness. Forty participants (mean age 19.13 ± 1.14 years, 21 men and 19 women) completed a stress (Trier Social Stress Test, TSST) and a control session in randomized order. Detection threshold to three odors varying in pleasantness (pleasant: ß-Citronellol; neutral: 2-Heptanol; unpleasant: 4-Methylpentanoic acid), odor discrimination, odor identification, sensitivity to trigeminal odor, and suprathreshold odor perception were assessed after participants' completion of the stress or the control tasks. Salivary cortisol, subjective stress, and heart rate were assessed throughout the experiment. After TSST, participants showed an increased sensitivity for the unpleasant odor. Moreover, there were correlations between stress-related salivary cortisol and the increased sensitivity for the unpleasant odor (r = 0.32, p = 0.05) and the neutral odor (r = 0.34, p < 0.05). Besides, salivary cortisol response was correlated to the increased odor discrimination performance (Δ stress - control) (r = 0.34, p < 0.05). The post-TSST perceived stress was correlated with decreased odor identification and decreased sensitivity to the unpleasant odor. After stress, participants rated lower pleasantness for ß-Citronellol than the control condition. Overall, these results suggest the impact of acute psychological stress on odor sensitivity depends on the odor valence, and that the stress-related cortisol responses may play an important role in this effect.

Salivary cortisol and cortisone in diagnosis of Cushing's syndrome - a comparison of six different analytical methods.

OBJECTIVES: Salivary cortisol and cortisone at late night and after dexamethasone suppression test (DST) are increasingly used for screening of Cushing's syndrome (CS). We aimed to establish reference intervals for salivary cortisol and cortisone with three liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques and for salivary cortisol with three immunoassays (IAs), and evaluate their diagnostic accuracy for CS. METHODS: Salivary samples at 08:00 h, 23:00 h and 08:00 h after a 1-mg DST were collected from a reference population (n=155) and patients with CS (n=22). Sample aliquots were analyzed by three LC-MS/MS and three IA methods. After establishing reference intervals, the upper reference limit (URL) for each method was used to calculate sensitivity and specificity for CS. Diagnostic accuracy was evaluated by comparing ROC curves. RESULTS: URLs for salivary cortisol at 23:00 h were similar for the LC-MS/MS methods (3.4-3.9 nmol/L), but varied between IAs: Roche (5.8 nmol/L), Salimetrics (4.3 nmol/L), Cisbio (21.6 nmol/L). Corresponding URLs after DST were 0.7-1.0, and 2.4, 4.0 and 5.4 nmol/L, respectively. Salivary cortisone URLs were 13.5-16.6 nmol/L at 23:00 h and 3.0-3.5 nmol/L at 08:00 h after DST. All methods had ROC AUCs ≥0.96. CONCLUSIONS: We present robust reference intervals for salivary cortisol and cortisone at 08:00 h, 23:00 h and 08:00 h after DST for several clinically used methods. The similarities between LC-MS/MS methods allows for direct comparison of absolute values. Diagnostic accuracy for CS was high for all salivary cortisol and cortisone LC-MS/MS methods and salivary cortisol IAs evaluated.

Assessment of salivary cortisol concentrations for procedural pain monitoring in newborns.

OBJECTIVES: The study aimed to evaluate the usefulness of salivary cortisol (SC) for the assessment of procedural pain intensity in preterm and term newborns. METHODS: Three groups of neonates (term, 370-416 weeks; moderate to late preterm, 320-366; and very preterm, <320) hospitalized in neonatal intensive care unit were assessed for the study. Response to nappy change, lung ultrasound (LUS), and blood sampling was analyzed. The intensity of pain was evaluated using continuous heart rate and blood oxygen saturation (SpO2) monitoring, Neonatal Infant Pain Scale (NIPS), and SC concentrations. Saliva samples were collected before and 20 min after the procedure's end. RESULTS: Seventy-one infants were examined: 30 term, 21 moderate to late preterm, and 20 very preterm. SC has increased significantly in response to nappy change only in very preterm newborns (2.13 ng/mL [1.55-3.68] vs. 2.84 ng/mL [1.93-9.06], p = 0.01). LUS did not affect concentrations of SC in any group. Significant increase in SC was observed after blood sampling in term and very preterm infants (2.2 ng/mL [1.45-2.92] vs. 4.29 ng/mL [3.88-5.73], p = 0.002, and 1.88 ng/mL [1.47-4.13] vs. 5.3 ng/mL [3.42-8.02], p = 0.002, respectively). A significant correlation between values of SC increase and NIPS scores was found (Spearman's rank correlation coefficient [rs] = 0.31, p = 0.001). CONCLUSIONS: We observed the increase in SC concentrations in response to painful stimulus. The presence of a correlation between NIPS scores and SC increase suggests that SC can be used as an objective parameter to assess pain in neonates.

Investigation of the effect of music listened to by patients with moderate dental anxiety during restoration of posterior occlusal dental caries.

OBJECTIVE: The aim of this randomized controlled study was to investigate the effect of music therapy during restorative dental treatments on patients with moderate dental anxiety. MATERIALS AND METHODS: Seventy patients were determined to have moderate dental anxiety by the Modified Dental Anxiety Scale (MDAS) and were divided randomly into two groups (n = 35). The first group did not listen to music during their restorative treatment (control group), and the second group listened to music of their choice (experimental group). Systolic blood pressure, diastolic blood pressure, heart rate, oxygen saturation, and body temperature were measured three times for each patient: once before the treatment, once after their dental caries were removed, and once at the end of the treatment. Salivary cortisol samples were taken from each patient before and after the treatment. The MDAS was re-administered to the patients at the end of the treatment, and the data were analyzed statistically. RESULTS: Only the diastolic blood pressure (P = 0.042) and the MDAS scores of the experimental group (P = 0.001) were significantly lower than the control group at the end of the treatment. CONCLUSION: While music listening did not have an effect on the physiologic parameters of the patients during restorative treatment, it decreased the MDAS scores of the patients. CLINICAL RELEVANCE: Although music therapy did not affect the physiological parameters during the restorative dental treatment, it may help to reduce patients' self reported anxiety level.

Religious Coping Is Differentially Associated with Physiological and Subjective Distress Indicators: Comparing Cortisol and Self-Report Patterns.

Use of religious coping in response to life stress is associated with improved mental and physical health outcomes. The aim of this study was to examine the influence of religious coping on conscious self-reported and non-conscious physiological stress responses to an acute, real-world stressor to better understand how this benefit may be conferred. This study examined the trajectory of subjective distress and cortisol patterns leading up to and following a stressful college exam using daily diary and ambulatory saliva samples, respectively (N students = 246). Religious coping was not significantly associated with subjective reports of distress. However, prior to the exam, greater use of religious coping was associated with an ostensibly more adaptive accelerated return to a cortisol baseline. This protective effect was no longer significant when the exam was over, suggesting that religious coping acts as a protective buffer against physiological stress responses rather than aiding in subjective recovery from stress.

The relationship between diurnal cortisol slope and cognitive development among children maltreated as infants.

Little is known about the role of hypothalamic-pituitary-adrenal (HPA) axis functioning for children's cognitive development, especially among vulnerable groups. The current study explores the relationship between diurnal cortisol slope and cognitive outcomes among children at the ages of 5 and 6 who have been maltreated as infants and involved with child protective services, using data from the National Survey of Child and Adolescent Well-Being (NSCAW) I (N=158). Multiple regression analyses showed that a greater decline in salivary cortisol from morning to evening was positively associated with scores on applied problems and expressive communication, even after adjustment for confounding. It was also associated with lower odds of cognitive disability. There were null associations with letter-word identification, passage comprehension, auditory comprehension, matrices, and vocabulary. Results suggest that children involved with child protective services as infants, and thus exposed early to likely 'toxic' levels of stressors, may face dysregulation of the HPA axis and particular difficulties in some aspects of cognitive function. Potential explanations and implications for policy are discussed.

The effect of virtual reality distraction on anxiety level during dental treatment among anxious pediatric patients: a randomized clinical trial.

This study evaluated the effect of Virtual Reality Distraction (VRD) on dental anxiety among anxious children undergoing prophylactic dental treatment by utilizing both subjective (Venham Anxiety and Behavioral Rating Scale (VABRS)) and objective (heart rate (HR) and salivary cortisol level (SCL)) measures. This randomized controlled study included 36 (6- to 14-year-old) healthy and anxious children who needed prophylactic dental treatment and had a history of previous dental treatment. The eligible children's anxiety level was evaluated using a modified version of the Abeer Dental Anxiety Scale-Arabic version (M-ACDAS) and those who scored at least 14 or more out of 21 were included. Participants were randomly distributed to either the VRD or control group. In the VRD group, participants wore the VRD eyeglasses during prophylactic dental treatment. In the control group, subjects received their treatment while watching a video cartoon on a regular screen. The participants were videotaped during the treatment, and their HR was recorded at four time points. Also, a sample from each participant's saliva was collected twice, at the baseline and after the procedure. The mean M-ACDAS score at baseline in the VRD and the control groups was not statistically significant (p = 0.424). At the end of the treatment, the SCL was significantly lower in the VRD group (p < 0.001). Neither the VABRS (p = 0.171) nor the HR significantly differed between the VRD and control groups. Virtual reality distraction is a non-invasive method that has the potential to significantly reduce anxiety during prophylactic dental treatment among anxious children.

Changes in the levels of marker molecules salivary α-amylase and cortisol as a stress response to everyday activities of general practitioners in rural areas of the Republic of Bulgaria.

INTRODUCTION: Stress is a phenomenon accompanying everyday life. Various reactions of the body are activated during stress, including activation of the hypothalamo-pituitary-adrenal endocrine axis and the autonomous nervous system. Their activity could be assessed by the measurement of biological stress marker molecules - salivary α-amylase and cortisol - on one side and heart rate, and blood pressure monitoring, on the other. The aim of the present study is to determine whether the daily professional routines cause stress development among general practitioners (GPs) who work in rural, distant areas in the territory of the Republic of Bulgaria. METHODS: One hundred and twenty-eight GPs were asked to answer a questionnaire to assess their health conditions, habits, priority objectives and interests, as well as their moral and ethical relationships with the patients. On this basis 40 participants were selected and outlined for the present survey (n=40, mean age 55.92±8.8). Four salivary samples were collected from each participant during 1 week: two on Monday (one in the morning and one after work) and two on Friday, by the same mechanism. The salivary samples collection was followed by measurement of blood pressure and pulse. This non-invasive survey was based on an ELISA method for quantitative determination of the marker molecules in saliva. The blood pressure and pulse were measured by blood pressure monitor. RESULTS: The levels of the salivary α-amylase were significantly higher at the end of the working day, especially on Friday (142.28±23.34 U/mL, p=0.018), but not between the beginning and the end of the week. The normal cortisol awakening response, characterized by a peak in the levels of cortisol after wake-up, followed by a slow decrease during the day, was detected only at the beginning of the week. The data show a significant impairment of this regularity at the end of the week. Moreover, the levels of cortisol, measured for the morning samples, show a decrease at the end of the week (25.73±10.51 ng/mL) in comparison to the beginning of the week (30.1±10.84, p=0.033). The analyses on the effect of smoking (p=0.002) and alcohol consumption (p=0.036) on stress development show a significant increase in the levels of the salivary α-amylase, but not on the levels of salivary cortisol. The changes in the blood pressure indicate stress development at the end of the week (p=0.04), while the pulse showed changes within a day rather than during the week. The values of the pulse were higher at the end of the day. CONCLUSION: The professional lives of the GPs who work in distant and rural places are associated with stress development. Different habits from the daily routine, such as alcohol consumption, smoking and physical activity, could be considered as modulators of stress development.

Relationships between weekly changes in salivary hormonal responses and load measures during the pre-season phase in professional male basketball players.

The aim of this study was to assess the relationships between weekly changes in external and internal load considered separately and jointly and salivary hormonal responses during the pre-season phase in professional male basketball players. Twenty-one professional male basketball players (mean ± standard deviation, age: 26.2 ± 4.9 years; height: 198.7 ± 6.7 cm; body mass: 93.2 ± 10.0 kg) were assessed during 5 weeks of the pre-season phase. External load was measured using microsensors and reported as PlayerLoad (PL) and PL/ min. Internal load was calculated using the session rating of perceived exertion scale (sRPE-load), summated heart rate zones (SHRZ) and percentage of maximal heart rate (%HRmax). Salivary hormone responses were monitored weekly by measuring testosterone (T), cortisol (C), and their ratio (T:C). The relationships between weekly changes in load measures considered separately and jointly and hormonal responses were assessed using linear mixed model analysis. No significant (p > 0.05) relationships were evident between weekly changes in T, C or T:C with external and internal load measures considered separately (R2-conditional = < 0.001-0.027) or jointly (R2-conditional = 0.028-0.075). Factors other than measured loads might be responsible for weekly changes in hormonal responses and therefore external and internal load measures cannot be used to anticipate weekly hormonal responses during the pre-season phase in professional basketball players.

Changes in psychological and cognitive variables as well as cortisol levels in recovered Covid-19 patients: a longitudinal study.

BACKGROUND: Decreased psychological and cognitive functioning is one of the complications of Covid-19 disease. We aimed to evaluate mental health, cognitive functioning, and salivary cortisol levels in Covid-19 patients with different disease severities in three 45-day intervals after recovery. METHODS: 258 Covid-19 patients were assigned into three groups based on their disease severity: 112 patients in mild group, 67 patients in moderate group and 79 patients in severe group. The participants underwent psychological evaluations (including Depression, Anxiety and Stress Scale questionnaire, Beck Depression Inventory, SpeilBerger State-Trait Anxiety Inventory, Pittsburgh Sleep Quality Inventory), cognitive assessments (The Paced Auditory Serial Addition Test) and salivary cortisol level evaluation in three 45-day periods. Non-parametric statistical methods were applied for psychological and cognitive indicators, while two-way mixed model ANOVA was used to evaluate the cortisol concentration in three replications. RESULTS: The group of mild patients became more anxious and the group of moderate patients became more anxious and depressed. But all three groups of patients developed severe sleep disorders over time. For cognitive functioning, although the results showed a decrease in the correct response rate, a significant increase in the correct response rate was observed in all three groups in all three measurements. However, the response speed not only did not increase, but also decreased in severe group. Cortisol level had a markedly increasing trend in all three groups. CONCLUSION: Improvement of cognitive functioning was in line with the increase in cortisol. Besides, the decrease in mental health had no effect on the cognitive functioning.