Monitoring adrenal insufficiency through salivary steroids: a pilot study.

BACKGROUND: Various glucocorticoid replacement therapies (GRTs) are available for adrenal insufficiency (AI). However, their effectiveness in restoring glucocorticoid rhythm and exposure lacks adequate biochemical markers. We described the diurnal salivary cortisol (SalF) and cortisone (SalE) rhythm among different GRTs and analysed the associations between saliva-derived parameters and life quality questionnaires. METHODS: Control subjects (CSs, n = 28) and AI patients receiving hydrocortisone (HC, n = 9), cortisone acetate (CA, n = 23), and dual-release hydrocortisone once (DRHC-od, n = 10) and twice a day (DRHC-td, n = 6) collected 9 saliva samples from 07:00 to 23:00. Patients compiled Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale, and Addison disease-specific quality-of-life questionnaires. SalE and SalF were measured by liquid chromatography-mass spectrometry. Exposure was monitored using SalE for HC and DRHC and SalF for CA. Area under the curve (AUC) was computed. Different GRTs were compared by Z-scores calculated from saliva-derived parameters. Questionnaire results predictors were evaluated with multiple regression analysis. RESULTS: Compared with controls, all GRTs resulted in glucocorticoid overexposure in the morning. Hydrocortisone, CA, and DRHC-td caused overexposure also in afternoon and evening. Compared with other treatments, CA determined increased Z-score-07:00 (P < .001), DRHC-td determined increased Z-score-AUC07:00→14:00 (P = .007), and DRHC-od induced lower Z-score-AUC14:00→23:00 (P = .015). Z-scores-AUC14:00→16:00 ≥ .619 best predicted questionnaire scores. CONCLUSIONS: None of the GRTs mimics normal glucocorticoid rhythmicity and exposure. SalE, SalF, and Z-score may be useful markers for monitoring and comparing different GRTs. Excess glucocorticoid in early afternoon best associated with depressive symptoms and worse life and sleep quality.

Salivary and serum biomarkers to evaluate psychological disorders in burning mouth syndrome: A systematic review and meta-analysis.

BACKGROUND: Burning mouth syndrome is a chronic pain syndrome mainly characterized by an intensive burning sensation of tongue. Previous studies have suggested that saliva/serum biomarkers in burning mouth syndrome might be associated with psychological disorders. The aim of systematic review was to observe whether the biomarkers in serum/saliva could be an alternative method to evaluate the psychological disorders in patients with burning mouth syndrome. MATERIALS AND METHODS: The PubMed, Embase, and Cochrane Library databases were searched for papers published up to March 15, 2023. Risk of bias was measured by using the Newcastle-Ottawa Scale. RevMan was used for meta-analysis. RESULTS: A total of 467 articles were screened, which of 12 studies were included. These studies collected 43 different biomarkers in saliva and 35 in serum. Of these biomarkers, only three (cortisol, α-amylase, and IL-6) were analyzed in two or more studies. Only salivary cortisol levels were significantly higher in the patient group compared to the controls (Mean Difference = 1.39; 95% CI [0.80-1.97]; p < 0.001). Moreover, cortisol might be relevant to psychological scores, especially anxiety. CONCLUSION: Different papers have investigated salivary and serum biomarkers in burning mouth syndrome patients with controversial results. This meta-analysis showed that cortisol levels in saliva may be a potential biomarker to assess the psychological disorders in burning mouth syndrome patients.

The effect of cognitive reappraisal and early-life maternal care on neuroendocrine stress responses.

Early-life adversity (ELA) is related to profound dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, reflected in both, blunted or exaggerated cortisol stress responses in adulthood. Emotion regulation strategies such as cognitive reappraisal might contribute to this inconsistent finding. Here, we investigate an interaction of early-life maternal care (MC), where low MC represents a form of ELA, and instructed emotion regulation on cortisol responses to acute stress. Ninety-three healthy young women were assigned to a low (n = 33) or high (n = 60) MC group, based on self-reported early-life MC. In the laboratory, participants received regulation instructions, asking to cognitively reappraise (reappraisal group, n = 45) or to focus on senses (control group, n = 48) during subsequent stress exposure, induced by the Trier Social Stress Test. Salivary cortisol and subjective stress levels were measured repeatedly throughout the experiment. Multilevel model analyses confirmed a MC by emotion regulation interaction effect on cortisol trajectories, while controlling for hormonal status. Individuals with low MC in the control compared with the reappraisal group showed increased cortisol responses; individuals with high MC did not differ. These results highlight the significance of emotion regulation for HPA axis stress regulation following ELA exposure. They provide methodological and health implications, indicating emotion regulation as a promising target of treatment interventions for individuals with a history of ELA.

Prenatal stress and hair cortisol in a sample of Latina women.

BACKGROUND: Stress during pregnancy adversely impacts maternal and infant health. Dysregulation of the hypothalamic pituitary axis is a mediator of the relationship between stress and health. Evidence supporting an association between prenatal chronic stress and cortisol is limited, and the majority of research published has been conducted amongst White participants, who experience less chronic stress than people of color. AIM: This study investigated associations between various measures of prenatal stress and hair cortisol concentrations which is a biomarker of the integrated stress response in a sample of Latina participants during the third trimester of pregnancy. METHOD: Pregnant women (n=45) were surveyed with scales measuring chronic stress, perceived stress, pregnancy-related and pregnancy-specific anxiety. Hair samples were collected as an objective neuroendocrine measure of chronic stress. Linear regression analyses were performed to assess associations between stress measures and hair cortisol. Pre-pregnancy BMI, smoking during pregnancy, and steroid use during pregnancy were used as covariates in adjusted models. RESULTS: Chronic stress, operationalized as maternal reports of neighborhood/housing strain, daily activities and relationship strain, discrimination, and financial strain, was significantly associated with higher hair cortisol concentrations. No significant associations were found between hair cortisol and perceived stress, pregnancy-related anxiety, nor pregnancy-specific anxiety in adjusted models. CONCLUSION: Chronic stress may be a more robust correlate of physiological stress, as measured by hair cortisol in pregnancy, than other common measures of prenatal stress and anxiety.

An LC-MS/MS-based method for the simultaneous quantification of melatonin, cortisol and cortisone in saliva.

Disturbances in the diurnal pattern are associated with several clinical and psychological conditions, including depression and fatigue. Salivary sampling for melatonin, cortisol and cortisone provides a non-invasive method for frequent sampling and obtaining biochemical insight into the diurnal pattern of individuals. Therefore, a new liquid chromatography-tandem mass spectrometry-based method for the measurement of salivary melatonin, cortisol and cortisone was developed and validated. The method required 250 µl saliva, used isotope dilution methodology and was based on a liquid-liquid extraction for sample preparation, reversed-phase chromatography and multiple reaction monitoring on a mass spectrometer for quantitation. The lower limits of quantification obtained were 0.010 nmol/L for melatonin, 0.5 nmol/L for cortisol and 1.00 nmol/L for cortisone and the limits of detection were 0.003 nmol/L, 0.15 nmol/L and 0.1 nmol/L respectively. The method imprecision was ≤14% for all measurands, and the method comparison showed highly comparable results with high correlation coefficients (all ≥0.964). Potential interference of cortisol and cortisone by prednisolone was observed and could be detected by chromatogram review. Typical diurnal patterns for melatonin, cortisol and cortisone were observed in the saliva of 20 cancer survivors who collected saliva throughout the day.

Prospective associations of technostress at work, burnout symptoms, hair cortisol, and chronic low-grade inflammation.

BACKGROUND: Working conditions in the age of digitalization harbor risks for chronic stress and burnout. However, real-world investigations into biological effects of technostress, that is stress in the context of digital technology use, are sparse. This study prospectively assessed associations between technostress, general work stress, burnout symptoms, hair cortisol, and chronic low-grade inflammation. METHODS: Hospital employees (N = 238, 182 females, Mage = 28.5 years) participated in a prospective cohort study with two follow-ups six months apart (T2, T3). Participants answered standardized questionnaires on general job strain (job demand-control ratio), technostressors (work interruptions, multitasking, information overload), burnout symptoms (exhaustion, mental distance), and relevant confounders. Moreover, they provided capillary blood samples for C-reactive protein (CRP) and hair strands for hair cortisol concentration (HCC) analysis. Structural equation modelling was performed. RESULTS: The factorial structure of survey measures was confirmed. Burnout symptoms (MT2 = 2.17, MT3 = 2.33) and HCC (MT2 = 4.79, MT3 = 9.56; pg/mg) increased over time, CRP did not (MT2 = 1.15, MT3 = 1.21; mg/L). Adjusted path models showed that technostress was negatively associated with HCC (ß = -0.16, p =.003), but not with burnout and CRP. General work stress in contrast, was not significantly associated with burnout, HCC or CRP. Furthermore, there were reciprocal effects of CRP on HCC (ß = 0.28, p =.001) and of HCC on CRP (ß = -0.10, p ≤.001). Associations were robust in additional analyses including further confounders. CONCLUSION: This is the first study on prospective effects of technostress on employees' endocrine and inflammatory systems. Results suggest differential effects of technostress on the hypothalamic-pituitary-adrenocortical axis activity. Given its key role for long-term health, the findings have important implications for occupational health and safety in digitalized work environments.

A stability indicating RP-HPLC-UV assay method for the simultaneous determination of hydroquinone, tretinoin, hydrocortisone, butylated hydroxytoluene and parabens in pharmaceutical creams.

Multicomponent drugs are medications that combine two or more active pharmaceutical ingredients in a single dosage form. These dosage forms improve the patient compliance, reduce the risk of drug interactions, and simplify dosing regimens. However, quality control of these multicomponent dosage forms can be challenging, especially if the final product contains four or more ingredients that are active (comprise stabilizers, preservatives, excipients, and other components). This problem can be more pronounced if the excipients can interfere with the analysis. In this work, a stability indicating assay method was developed and validated (according to the ICH International Guidelines) for the simultaneous determination of hydroquinone (HQ), tretinoin (TRT), hydrocortisone (HCA), butylated hydroxytoluene (BHT), methyl paraben (MP) and propyl paraben (PP) in commercially available pharmaceutical creams. The proposed method is based on gradient elution using X-Bridge C18 (150 × 4.6 mm, 5 µm) column with a flow rate of 1 mL/min. The linear ranges (µg/mL) were 240-560 for HQ, 24-56 for MP, 132-308 for HCA, 6-14 for PP, 12-28 for BHT, 6.6-15 for TRT. During the validation process, the intra- and interday precision and trueness (evaluated as recovery) were found to be below 2.0% and between 100-102%, respectively. System suitability tests (SST) allow validating the herein proposed procedure specifically for pharmaceutical and industrial applications. SST test shows that the reported procedure fulfill with the Guidelines, allowing excellent separation of the analytes with very sensitive, accurate (precise and true) and reproducible quantitation of each analytes. The method was successfully applied in forced degradation studies of the six analytes. Specifically, acid degradation slightly affected HCA and BHT (91% recovery), while alkaline degradation drastically reduced HCA recovery (5.5%) and moderately affected BHT (85%). Photodegradation primarily influenced TRT quantity, and oxidative degradation intensified the BHT peak (130%).

Prenatal exposure to social adversity and infant cortisol in the first year of life.

Exposure to social adversity has been associated with cortisol dysregulation during pregnancy and in later childhood; less is known about how prenatal exposure to social stressors affects postnatal cortisol of infants. In a secondary analysis of data from a longitudinal study, we tested whether a pregnant woman's reports of social adversity during the third trimester were associated with their infant's resting cortisol at 1, 6, and 12 months postnatal. Our hypothesis was that prenatal exposure to social adversity would be associated with elevation of infants' cortisol. Measures included prenatal survey reports of social stressors and economic hardship, and resting cortisol levels determined from infant saliva samples acquired at each postnatal timepoint. Data were analyzed using linear mixed effects models. The final sample included 189 women and their infants (46.56% assigned female sex at birth). Prenatal economic hardship was significantly associated with infant cortisol at 6 months postnatal; reports of social stressors were not significantly associated with cortisol at any time point. Factors associated with hardship, such as psychological distress or nutritional deficiencies, may alter fetal HPA axis development, resulting in elevated infant cortisol levels. Developmental changes unique to 6 months of age may explain effects at this timepoint. More work is needed to better comprehend the complex pre- and post-natal physiologic and behavioral factors that affect infant HPA axis development and function, and the modifying role of environmental exposures.

Hair cortisol concentration and its association with acute stress responses and recovery in a sample of medical students in Germany.

INTRODUCTION: Experiencing acute and chronic stress can contribute to adverse health outcomes. Responses to acute stress differ between individuals (i.e., stress reactivity) and the experience of chronic stress has been discussed to be associated with acute stress responses and stress recovery. This study thus aims to investigate whether hair cortisol concentration (HCC), being an indicator for hypothalamus-pituitary-adrenal (HPA) axis activity over a prolonged period of time, is associated with acute stress responses and recovery in a sample of medical students. MATERIAL AND METHODS: From July 2020 to July 2021, medical students (n = 54) underwent a virtual-reality Trier Social Stress Test in which their blood pressure and heart rate variability (HRV) were measured, and hair samples were taken to determine HCC. Piecewise linear growth analyses were used to investigate whether HCC (categorized into low, medium and high levels) is associated with acute stress responses and recovery regarding blood pressure and HRV. RESULTS: Significant interaction effects in piecewise linear growth analyses showed that participants with higher levels of HCC had lower systolic and diastolic blood pressure responses compared to participants with medium levels of HCC. No significant interaction effects were observed for HRV responses or for recovery measures. CONCLUSIONS: The study suggests that higher levels of HCC are associated with a lower cardiovascular response in terms of blood pressure to an acute stressor in medical students. Therefore, long-term HPA-axis activity may contribute to different magnitudes of acute stress responses in the autonomic nervous system. As the shown lower blood pressure responses to acute stress in individuals with increased long-term HPA-axis activity may represent inadequate stress responses, these should be further studied in order to find out more about their interaction and potential subsequent disease risks.

Comparison of the Perceived Stress Reactivity Scale with physiological and self-reported stress responses during ecological momentary assessment and during participation in a virtual reality version of the Trier Social Stress Test.

Valid approaches to conveniently measure stress reactivity are needed due to the growing evidence of its health-impairing effects. This study examined whether the Perceived Stress Reactivity Scale (PSRS) predicts cardiovascular and psychological responses to psychosocial stressors during daily life and during a virtual reality (VR) Trier Social Stress Test (TSST). Medical students answered a standardized baseline questionnaire to assess perceived stress reactivity by the PSRS. The PSRS asks participants to rate the intensity of their typical affective responses to common stressors during daily life. They were further asked to participate in a VR-TSST and in an ecological momentary assessment (EMA) over a period of three consecutive workdays during daily life. Blood pressure and self-reported stress were repeatedly, heart rate variability (HRV) continuously measured during the VR-TSST and EMA. Furthermore, participants repeatedly assessed task demands, task control and social conflict during the EMA. Data was analysed using multilevel analysis and multiple linear regression. Results indicate that the PSRS moderates associations between blood pressure (but not HRV) and demands and control during daily life. Furthermore, the PSRS directly predicted self-reported stress, but did not moderate associations between self-reported stress and demands, control and social conflict. The PSRS did not predict physiological and self-reported stress responses to the VR-TSST. This study partly confirmed convergent validity of the PSRS to stress reactivity in daily life. Furthermore, the lack of association between the PSRS and stress responses to the VR-TSST calls for future studies to search for reliable and valid ways to assess stress reactivity.

The influence of selected factors on wool cortisol concentration in alpacas (Vicugna pacos).

Several internal and external factors can influence animals' hormonal activity. Cortisol level in hair and wool determines chronic stress, which is connected with the long-term HPA axis effect. Wool cortisol levels in alpacas have never been determined to this time. The study aimed to assess the influence of selected factors on wool cortisol concentration in alpacas. The study included 36 alpacas. Wool samples were collected during shearing in June 2021, cut with an electric clipper from the right shoulder and the rump. Wool samples were fragmented into proximal (winter-spring regrowth) and distal (summer-fall regrowth) segments. Alpacas' Heat Stress Index (HSI) for the summer of 2020 was 139.4, and 116 for the winter of 2021. The cortisol levels in the wool samples were determined with the General Cortisol ELISA Kit assay. The most significant differences in wool cortisol concentrations were caused by two factors: the wool segment (P < 0.001; η2 = 0.889) and the region on the body (P < 0.001; η2 = 0.876). Wool cortisol level was higher in the distal segment (referring to the summer-fall season) than in the proximal one (referring to the winter-spring season). It is suggested that alpacas can feel heat stress in summer (HSI = 139.4), which could influence higher cortisol levels in the distal segment. The wool cortisol level was higher in the rump samples than the shoulder ones. Therefore, it is essential in future studies that wool samples from all tested animals should be completed from the same body region. Differences among age and sex groups were also observed. Wool cortisol level was higher in older animals, as differences between age groups were observed in samples from the rump in the distal and proximal segments (distal, the rump younger*older: P < 0.001; η2 = 0.321; proximal, the rump older*younger: P = 0.007; η2 = 0.195). Males showed higher cortisol levels than females, as a difference between sexes was observed in samples from the rump in the proximal segment (P = 0.001, η2 = 0.271). This study emphasizes that various factors may significantly influence wool cortisol levels, which can be helpful in alpacas' welfare estimation using this hormonal indicator as a noninvasive long-term stress assessment method.

Extensive comparison of salivary collection, transportation, preparation, and storage methods: a systematic review.

BACKGROUND: Human saliva as a bodily fluid-similar to blood-is utilized for diagnostic purposes. Unlike blood sampling, collecting saliva is non-invasive, inexpensive, and readily accessible. There are no previously published systematic reviews regarding different collection, transportation, preparation, and storage methods for human saliva. DESIGN: This study has been prepared and organized according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 guidelines. This systematic review has been registered at PROSPERO (Registration ID: CRD42023415384). The study question according to the PICO format was as followed: Comparison of the performance (C) of different saliva sampling, handling, transportation, and storage techniques and methods (I) assessed for analyzing stimulated or unstimulated human saliva (P and O). An electronic search was executed in Scopus, Google Scholar, and PubMed. RESULTS: Twenty-three descriptive human clinical studies published between 1995 and 2022 were included. Eight categories of salivary features and biomarkers were investigated (i.e., salivary flow rate, total saliva quantity, total protein, cortisol, testosterone, DNA quality and quantity, pH and buffering pH). Twenty-two saliva sampling methods/devices were utilized. Passive drooling, Salivette®, and spitting were the most utilized methods. Sampling times with optimum capabilities for cortisol, iodine, and oral cancer metabolites are suggested to be 7:30 AM to 9:00 AM, 10:30 AM to 11:00 AM, and 14:00 PM to 20:00 PM, respectively. There were 6 storage methods. Centrifuging samples and storing them at -70 °C to -80 °C was the most utilized storage method. For DNA quantity and quality, analyzing samples immediately after collection without centrifuging or storage, outperformed centrifuging samples and storing them at -70 °C to -80 °C. Non-coated Salivette® was the most successful method/device for analyzing salivary flow rate. CONCLUSION: It is highly suggested that scientists take aid from the reported categorized outcomes, and design their study questions based on the current voids for each method/device.

Nociception related biomolecules in the adult human saliva: A scoping review with additional quantitative focus on cortisol.

Nociception related salivary biomolecules can be useful patients who are not able to self-report pain. We present the existing evidence on this topic using the PRISMA-ScR guidelines and a more focused analysis of cortisol change after cold pain induction using the direction of effect analysis combined with risk of bias analysis using ROBINS-I. Five data bases were searched systematically for articles on adults with acute pain secondary to disease, injury, or experimentally induced pain. Forty three articles met the inclusion criteria for the general review and 11 of these were included in the cortisol-cold pain analysis. Salivary melatonin, kallikreins, pro-inflammatory cytokines, soluable TNF-α receptor II, secretory IgA, testosterone, salivary α-amylase (sAA) and, most commonly, cortisol have been studied in relation to acute pain. There is greatest information about cortisol and sAA which both rise after cold pain when compared with other modalities. Where participants have been subjected to both pain and stress, stress is consistently a more reliable predictor of salivary biomarker change than pain. There remain considerable challenges in identifying biomarkers that can be used in clinical practice to guide the measurement of nociception and treatment of pain. Standardization of methodology and researchers' greater awareness of the factors that affect salivary biomolecule concentrations are needed to improve our understanding of this field towards creating a clinically relevant body of evidence.

Black Phosphorus-Based Reusable Biosensor Platforms for the Ultrasensitive Detection of Cortisol in Saliva.

A black phosphorus (BP)-based reusable biosensor platform is developed for the repeated and real-time detection of cortisol using antibody-conjugated magnetic particle (MP) structures as a refreshable receptor. Here, we took advantage of the low-noise characteristics of a mechanically exfoliated BP-based field-effect transistor (FET) and hybridized it with anti-cortisol antibody-functionalized MPs to build a highly sensitive cortisol sensor. This strategy allowed us to detect cortisol down to 1 aM in real time and discriminate cortisol from other hormones. In this case, we could easily remove MPs with used antibodies from the surface of a BP-FET and reuse the chip for up to eight repeated sensing operations. Moreover, since our platform could be fabricated using conventional photolithography techniques and the sensor can be reused multiple times, one should be able to significantly reduce operation costs for practical applications. Furthermore, this method could be utilized to detect different hormones with high sensitivity and selectivity in complex environments such as artificial saliva solutions. In this respect, our reusable BP-FET biosensing platform can be a powerful tool for versatile applications such as clinical diagnosis and basic biological analysis by conjugating various antibodies.

A cross-sectional study observing the association of psychosocial stress and dietary intake with gut microbiota genera and alpha diversity among a young adult cohort of black and white women in Birmingham, Alabama.

BACKGROUND: The relationships between psychosocial stress and diet with gut microbiota composition and diversity deserve ongoing investigation. The primary aim of this study was to examine the associations of psychosocial stress measures and dietary variables with gut microbiota genera abundance and alpha diversity among young adult, black and white females. The secondary aim was to explore mediators of psychosocial stress and gut microbiota diversity and abundance. METHODS: Data on 60 females who self-identified as African American (AA; n = 29) or European American (EA; n = 31) aged 21-45 years were included. Cortisol was measured in hair and saliva, and 16S analysis of stool samples were conducted. Discrimination experiences (recent and lifetime), perceived stress, and depression were evaluated based on validated instruments. Spearman correlations were performed to evaluate the influence of psychosocial stressors, cortisol measures, and dietary variables on gut microbiota genus abundance and alpha diversity measured by amplicon sequence variant (ASV) count. Mediation analyses assessed the role of select dietary variables and cortisol measures on the associations between psychosocial stress, Alistipes and Blautia abundance, and ASV count. RESULTS: AA females were found to have significantly lower ASV count and Blautia abundance. Results for the spearman correlations assessing the influence of psychosocial stress and dietary variables on gut microbiota abundance and ASV count were varied. Finally, diet nor cortisol was found to partially or fully mediate the associations between subjective stress measures, ASV count, and Alistipes and Blautia abundance. CONCLUSION: In this cross-sectional study, AA females had lower alpha diversity and Blautia abundance compared to EA females. Some psychosocial stressors and dietary variables were found to be correlated with ASV count and few gut microbiota genera. Larger scale studies are needed to explore the relationships among psychosocial stress, diet and the gut microbiome.

Examining surgeon stress in robotic and laparoscopic surgery.

Robotic surgery may decrease surgeon stress compared to laparoscopic. To evaluate intraoperative surgeon stress, we measured salivary alpha-amylase and cortisol. We hypothesized robotic elicited lower increases in surgeon salivary amylase and cortisol than laparoscopic. Surgical faculty (n = 7) performing laparoscopic and robotic operations participated. Demographics: age, years in practice, time using laparoscopic vs robotic, comfort level and enthusiasm for each. Operative data included operative time, WRVU (surgical "effort"), resident year. Saliva was collected using passive drool collection system at beginning, middle and end of each case; amylase and cortisol measured using ELISA. Standard values were created using 7-minute exercise (HIIT), collecting saliva pre- and post-workout. Linear regression and Student's t test used for statistical analysis; p values < 0.05 were significant. Ninety-four cases (56 robotic, 38 laparoscopic) were collected (April-October 2022). Standardized change in amylase was 8.4 ± 4.5 (p < 0.001). Among operations, raw maximum amylase change in laparoscopic and robotic was 23.4 ± 11.5 and 22.2 ± 13.4; raw maximum cortisol change was 44.21 ± 46.57 and 53.21 ± 50.36, respectively. Values normalized to individual surgeon HIIT response, WRVU, and operative time, showing 40% decrease in amylase in robotic: 0.095 ± 0.12, vs laparoscopic: 0.164 ± 0.16 (p < 0.02). Normalized change in cortisol was: laparoscopic 0.30 ± 0.44, robotic 0.22 ± 0.4 (p = NS). On linear regression (p < 0.001), surgeons comfortable with complex laparoscopic cases had lower change in normalized amylase (p < 0.01); comfort with complex robotic was not significant. Robotic may be less physiologically stressful, eliciting less increase in salivary amylase than laparoscopic. Comfort with complex laparoscopic decreased stress in robotic, suggesting laparoscopic experience is valuable prior to robotic.

Sex differences in cortisol levels in depression: A systematic review and meta-analysis.

Higher prevalence of depression in females might be associated with sex-specific cortisol levels. Evidence exists that cortisol levels differ between healthy females and males, however a sex-specific association in depression has not been systematically assessed. Thus, the current study quantifies the existing literature on different cortisol parameters, i.e., basal cortisol, hair cortisol, cortisol awakening response (CAR), and cortisol stress reactivity comparing depressed females and males as well as sex-specific comparisons with healthy controls. Following an extensive literature research, fifty original articles were included. Depressed females had significantly higher hair cortisol, higher CAR, and lower cortisol stress reactivity compared to depressed males. In comparison with sex-matched controls, female patients had significantly higher evening basal cortisol, higher CAR and lower cortisol stress reactivity, and male patients had significantly higher general, morning and evening basal cortisol. Overall, sex as a fundamental driver of cortisol levels in depression needs to be taken into account.

Cortisol and changes in depressive symptoms: The moderating role of DHEA.

Stress is associated with activation of the hypothalamus-adrenal-axis (HPA). Cortisol, a product of the HPA, is thought to predict depression. However, to date, the majority of studies investigating the cortisol-depression relationship have been cross-sectional and results have been mixed. One possible reason for these mixed findings, may be that many studies fail to consider the moderating role of dehydroepiandosterone (DHEA), which is released alongside cortisol and is thought to serve opposing functions. Therefore, the present study investigated the main and interactive effects of cortisol and DHEA on depressive symptoms. Salivary cortisol and DHEA were measured from saliva throughout the Trier Social Stress task for N = 417 participants at baseline. Participants reported on their depressive symptoms using the Beck Depression Inventory - II at both baseline and follow up (ranging from 1-20 months post baseline; M = 11.60, SD = 5.80) as well as general demographics. The lavaan package in R (version 0.6.11; Rosseel, 2012) was used to conduct multiple regression analyses with FIML to explore the relationships between these variables. Results demonstrated no main effect of cortisol or DHEA, but did show a significant interaction with DHEA. The relations between cortisol and depressive symptoms depended on levels of DHEA such that the relationship was positive at low and negative at high levels of DHEA, with the overall interaction significant (ß = -.22, p < .001, 95% CI = [-.333, -.115]). DHEA can act as a protective factor against depression when cortisol levels are high. This presents opportunities for future research on how to improve DHEA levels to potentially reduce depression.

Influence of controlled environmental conditions in potential salivary ocular pain biomarkers for enhancing the assessment of ocular pain.

PURPOSE: We endeavored to identify objective salivary biomarkers for pain, a subjective sensation with a biological basis, using molecules already described related to pain. The study aimed to analyze inter-individual differences and intersession variability in salivary potential ocular pain biomarkers on healthy subjects, in samples obtained under the influence of controlled environmental conditions. METHODS: Thirty-four healthy subjects, 20 male, 14 female, median age 35.44 years (range 30-40) were exposed for 30 minutes under standard environmental conditions (T: 22°C, 50% relative humidity) in the Controlled Environmental Research Laboratory (CE-Lab, Vision R&D, Valladolid Spain) in two separate visits (V1, V2) at least 24 hours apart. Saliva was collected after the exposure in each of the visits, and cortisol, α-amylase (sAA), secretory IgA (sIgA), testosterone, and soluble fraction of TNFα receptor II (sTNFαRII) were analyzed by ELISA. Repeatability of inter-subject inter-session measurements was assayed by intraclass correlation coefficient (ICC). RESULTS: There were no significant inter-session differences in testosterone (p = 0.2497), sTNFαRII (p = 0.6451) and sIgA (p = 0.9689) salivary levels. The reproducibility for salivary cortisol, sAA, testosterone, sTNFαRII and sIgA were 0.98 ng/ml, 20.58 U/ml, 21.07 µg/ml, 24.68 pg/ml and 0.19 pg/ml, respectively. Salivary cortisol, sAA, testosterone, sTNFαRII and sIgA yielded the following ICCs: 0.506, 0.569, 0.824, 0.870 and 0.4295, respectively; all these ICCs (except that for cortisol and sIgA) were found to be improved compared to those found previously by our group in a previous study in salivary samples obtained from healthy subjects under non-controlled environmental conditions; Cortisol´s ICC didn´t improve and was in both cases at the limit of acceptability. CONCLUSION: Environmental factors such as temperature and relative humidity affect the reproducibility of measurement of some salivary molecules which have been proposed as potential pain biomarkers. The exposure of subjects to standard controlled environmental conditions before salivary sample obtention would improve the reproducibility of these molecule measures' as potential biomarkers of chronic ocular pain.

Quantification of prohibited substances and endogenous corticosteroids in saliva using traditional, alternative microextraction-based, and novel 3D printed sample-preparation methods coupled with LC-MS.

Oral fluid has gained significant interest as an alternative matrix for drug testing due to its easy and non-invasive collection. Despite these advantages, achieving suitably low limits of detection remains a clear challenge in the use of oral fluids for drug screening. In this study, we demonstrate that the application of commercially available SPME fibers followed by liquid chromatography tandem mass spectrometry can enable the comprehensive detection and confirmation of drugs in oral fluid samples. To this end, we develop and test a sample-preparation protocol for a panel of 46 drugs covering the most popular drugs of abuse and doping agents available worldwide. Human saliva samples were collected using a Salivette® device (CE IVD certified) and sampled using SPME devices coated with a C18 extraction phase. The proposed protocol was validated with respect to its lower limits of quantification (LLOQ), linearity, matrix effects, precision, and extraction recovery. Linearity was confirmed for all compounds (R2 > 0.97), except for testosterone (R2 = 0.953) and metandrostenolon (R2 = 0.958). Furthermore, 4 compounds suffered from matrix effects, with less than 10 % deviation from acceptance criteria. After analytical validation, saliva samples from volunteers were analyzed to determine free concentrations of cortisol at different times after awaking. Finally, a 3D-printed prototype device was designed and successfully applied to extract small molecules, thus demonstrating a new modern low-cost approach for bioanalysis.