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Objectives: This study aimed to investigate the potential reduction of academic stress related to a graded oral presentation in postgraduate dental students using coffee aromatherapy., Methods: Healthy postgraduate dental students in a seminar class were divided into coffee (n = 32) and control (n = 26) groups. There were 3 modes of aroma distribution: personal distribution with a coffee pad attached to a lanyard, a lanyard plus a personal fan for ventilation of the aroma, and the typical method of the diffuser to spread the aroma in the ambient air. Stress markers comprised levels of salivary alpha-amylase (sAA), cortisol (sCort), and chromogranin A (sCgA). Pulse rates were also measured., Results: Levels of sAA increased 176.62% ± 30.26% between pre- and postpresentation in the control group. Inhaling coffee aroma during the presentation period significantly ameliorated sAA increase at 81.02% ± 14.90% (P = .015). sCort levels tended to decrease in the coffee group, but not significantly. Surprisingly, sCgA levels increased more in the coffee group. Also, pulse rates decreased in the coffee group (-2.07 ± 2.81 bpm) and increased in the control group (6.90 ± 3.22 bpm; P = .035). Subgroup analysis did not reveal differences in salivary markers amongst the 3 aroma distribution modes., Conclusions: Coffee aroma could have an anxiolytic effect on postgraduate dental students, as evidenced by changes in sAA levels and pulse rates. Personal aroma distribution was also a useful and effective mode of aromatherapy., Competing Interests: Conflict of interest None disclosed., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The activity of the enzyme 11β-hydroxysteroid dehydrogenase type II (11β-HSD type II), which can be estimated by the combined measurement of cortisol and cortisone, is gaining importance as a marker for the assessment of stress in pigs. The aim of this study was to investigate the activity of this enzyme and the salivary concentrations of cortisol and cortisone in pigs during pregnancy, farrowing and lactation and to compare it with other stress-related biomarkers such as Chromogranin A (CgA), S100A12 and alpha-amylase. Salivary cortisone concentrations and 11β-HSD type II activity decreased after farrowing, while cortisol concentrations increased. Enzyme activity did not show significant correlations with any of the other stress-related biomarkers measured in this study. Overall, the results of this report indicate a different regulation of 11β-HSD type II activity and of cortisol and cortisone during pregnancy and lactation, which should be considered when evaluating these analytes in saliva during these periods., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Maternal stress influences in utero brain development and is a modifiable risk factor for offspring psychopathologies. Reward circuitry dysfunction underlies various internalizing and externalizing psychopathologies. This study examined (1) the association between maternal stress and microstructural characteristics of the neonatal nucleus accumbens (NAcc), a major node of the reward circuitry, and (2) whether neonatal NAcc microstructure modulates individual susceptibility to maternal stress in relation to childhood behavioral problems., Method: K-means longitudinal cluster analysis was performed to determine trajectories of maternal stress measures (Perceived Stress Scale [PSS], hair cortisol) from preconception to the third trimester. Neonatal NAcc microstructural measures (orientation density index [ODI] and intracellular volume fraction [ICVF]) were compared across trajectories. We then examined the interaction between maternal stress and neonatal NAcc microstructure on child internalizing and externalizing behaviors, assessed between ages 3 and 4 years., Results: Two trajectories of maternal stress magnitude ("low"/"high") were identified for both PSS (n = 287) and hair cortisol (n = 336). Right neonatal NAcc ODI (rNAcc-ODI) was significantly lower in "low" relative to "high" PSS trajectories (n = 77, p = .04). PSS at preconception had the strongest association with rNAcc-ODI (r = 0.293, p = .029). No differences in NAcc microstructure were found between hair cortisol trajectories. A significant interaction between preconception PSS and rNAcc-ODI on externalizing behavior was observed (n = 47, p = .047)., Conclusion: Our study showed that the preconception period contributes to in utero NAcc development, and that NAcc microstructure modulates individual susceptibility to preconception maternal stress in relation to externalizing problems., Plain Language Summary: In the S-PRESTO population-based cohort study conducted in Singapore with 351 women and their children, higher levels of maternal perceived stress within the year before pregnancy were associated with increased dendritic complexity within offsprings' nucleus accumbens, indicative of a more advanced developmental profile. Variations in right nucleus accumbens microstructure significantly modulated the association between maternal perceived stress at preconception and externalizing behaviors in early childhood. Study findings suggest that maternal stress in the preconception period accelerates in-utero nucleus accumbens development, leading to differential risk to externalizing problems in later childhood., (Copyright © 2024 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

While researchers and practitioners attribute an essential role to executive functions (EFs) for soccer performance, the usefulness of respective diagnostics and the predictive value remain unclear. One limitation restricting the translation and relevance of study results to improve actual game performance is the insufficient consideration of competitive conditions. Thus, this study aimed to conduct soccer-specific cognitive diagnostics under a soccer-specific psychophysiological stress condition, mimicing the demands of a competitive game. A total of 92 (M age  = 15.17, SD age  = 1.45) youth elite players performed tests for inhibition (flanker task) or cognitive flexibility (number-letter task) with a soccer-specific motor response (i.e., pass into goals). After a pre-test in a neutral condition, players were randomly assigned to a neutral (moderate soccer-specific exercise) or a stress condition (physical stress and competitive instructions and filming for psychological stress). Objective (i.e., cortisol, heart rate variability) and subjective stress-related measures (i.e., SAM, VAS) were assessed six times throughout experimental procedure. Analyses revealed significant interaction effects between time and condition for all objective and subjective variables indicating a successful experimental stress induction. For cognitive performance, results revealed significant main effects of time, but no significant interaction effects between time and condition. However, descriptive statistics suggested improved performance under stress, with decreased flanker effect and switch costs. Additionally, response time variability in the flanker task significantly decreased in the stress condition. These findings offer insights into individual stress perception and processing under game-related psychophysiological demands, expanding previous research on situational EF alterations that also hold relevance for applied practitioners., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The pathophysiology of Takotsubo syndrome (TTS) is not completely understood and the role of chronic stress is among the main mechanistic links. The aim of this study was to explore whether accumulating hair cortisol concentration (HCC), a novel biomarker of chronic stress, is associated with the occurrence of TTS., Methods: A consecutive series of 18 TTS patients and 36 age and sex matched healthy controls were included in our analysis. Hair samples were collected from participants'' vertex. The proximal 2.5 cm of hair was cut in equal parts of 0.5 cm, reflecting mean cortisol levels in time intervals of 0-15, 15-30, 30-45, 45-60 and 60-75 days prior to hair collection., Results: HCC was higher in TTS group compared to controls at any time point and increased over time starting from 75 days prior to the event. The rate of HCC increase was significantly higher in TTS patients versus controls (beta of interaction = 0.48; 95%CI: 0.36-0.60; p < 0.001)., Conclusions: The steadily increasing trend of HCC in TTS patients suggests that the additive effect of multiple stressful events over several weeks prior TTS onset may disrupt cortisol homeostasis and play a role in TTS pathophysiology., Competing Interests: Declaration of competing interest The authors report there are no competing interests to declare., (Copyright © 2023. Published by Elsevier B.V.)

Enhancing stress resilience through the early life period in pigs could potentially improve pork quality. It was hypothesised that pigs receiving maternal contact or positive human contact during lactation would have improved carcass and pork quality. Seventy-nine mixed-sex pigs were selected from a 2 × 2 factorial randomised block design for treatments maternal contact (MC+) / reduced maternal contact (MC-); and positive human contact (HC+) / control (HC-). Modified farrowing crates were utilised to reduce maternal contact (MC-). Litters in the HC+ treatment received five minutes of daily positive human interaction (stroking). Treatments ceased at 22 days of age (weaning) and pigs were slaughtered after 21 weeks of age. The m. longissimus thoracis et lumborum pH was higher in HC+ than HC- pigs (P < 0.05) during chilling, from 90 min post slaughter. No HC effects (P > 0.05) were observed for cortisol or haptoglobin concentration, hot carcass weight, P2 backfat, carcass scratches, colour, drip loss, cook loss and shear force. MC+ tended (P < 0.086) to increase carcass weight, P2 and carcass scratch score compared to MC-, but no further impacts were observed. The impact of positive human contact during early life was observed 20+ weeks after treatment with reduced pH decline, potentially indicating a reduction in pre-slaughter stress, however there were no further impacts on pork quality. There is evidence that maternal contact is important for lifetime growth performance of pigs but the impacts on stress resilience are less apparent., Competing Interests: Declaration of competing interest This study received funding from the Australian Research Council (LP180100218) and Australasian Pork Research Institute Limited. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. All authors declare no other competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Recently, stress has been recognized as a key factor in the emergence of individual and social issues. Numerous attempts have been made to develop sensor-augmented psychological stress detection techniques, although existing methods are often impractical or overly subjective. To overcome these limitations, we acquired a dataset utilizing both wireless wearable multimodal sensors and salivary cortisol tests for supervised learning. We also developed a novel deep neural network (DNN) model that maximizes the benefits of sensor fusion., Method: We devised a DNN involving a shuffled efficient channel attention (ECA) module called a shuffled ECA-Net, which achieves advanced feature-level sensor fusion by considering inter-modality relationships. Through an experiment involving salivary cortisol tests on 26 participants, we acquired multiple bio-signals including electrocardiograms, respiratory waveforms, and electrogastrograms in both relaxed and stressed mental states. A training dataset was generated from the obtained data. Using the dataset, our proposed model was optimized and evaluated ten times through five-fold cross-validation, while varying a random seed., Results: Our proposed model achieved acceptable performance in stress detection, showing 0.916 accuracy, 0.917 sensitivity, 0.916 specificity, 0.914 F1-score, and 0.964 area under the receiver operating characteristic curve (AUROC). Furthermore, we demonstrated that combining multiple bio-signals with a shuffled ECA module can more accurately detect psychological stress., Conclusions: We believe that our proposed model, coupled with the evidence for the viability of multimodal sensor fusion and a shuffled ECA-Net, would significantly contribute to the resolution of stress-related issues., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Cortisol is a well-known stress biomarker; this study focuses on using electrochemical immuno-sensing to measure the concentration of cortisol selectively and sensitively in artificial samples. Anti-cortisol antibodies have been immobilised on polycrystalline Au electrodes via strong covalent thiol bonds, fabricating an electrochemical bio-immunosensor for cortisol detection. IrO x was then anodically electrodeposited as a reference electrode on a commercial screen-printed electrode and electrochemical impedance spectrometry (EIS) studies were used to correlate the electrochemical response to cortisol concentration and the induced changes in charge transfer resistance (R ct ). A linear relationship between the R ct and the logarithm of cortisol concentration was found in concentrations ranging from 1 ng/mL to 1 mg/mL with limit of detection at 11.85 pg/mL (32.69 pM). The modification of the reference electrode with iridium oxide has greatly improved the reproducibility of the screen-printed electrode. The sensing system can provide a reliable and sensitive detection approach for cortisol measurements., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Cortisol, a crucial steroid hormone synthesized by the adrenal glands, has diverse impacts on multiple physiological processes, such as metabolism, immune function, and stress management. Disruption in cortisol levels can result in conditions like Cushing's syndrome and Addison's disease. This review provides an in-depth exploration of cortisol, covering its structure, various forms in the body, detection methodologies, and emerging trends in cancer treatment and detection. Various techniques for cortisol detection, including electrochemical, chromatographic, and immunoassay methods were discussed and highlighted for their merits and applications. Electrochemical immunosensing emerges as a promising approach, which offered high sensitivity and low detection limits. Moreover, the review delves into the intricate relationship between cortisol and cancer, emphasizing cortisol's role in cancer progression and treatment outcomes. Lastly, the utilization of biomarkers, in-silico modeling, and machine learning for electrochemical cortisol detection were explored, which showcased innovative strategies for stress monitoring and healthcare advancement., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Substance use is highly prevalent among women experiencing intimate partner violence (IPV) and has been associated with dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis and resulting cortisol response. Posttraumatic stress disorder (PTSD) symptoms may play an important role in exacerbating the association between cortisol levels and substance use behaviors., Purpose: This study examined the role of PTSD symptoms in the relation between cortisol and past month substance use behaviors. The current study used hair cortisol as an index of past 30-day HPA-axis functioning and ecological momentary assessment (EMA) to characterize substance use behaviors more accurately over a 30-day period., Method: Participants were 90 community women who had experienced physical or sexual IPV in the past 30 days by their current male partner and used any amount of alcohol or drugs (M age = 40.71; 54.4 % white). Participants completed (a) a baseline interview, (b) EMA for 30-days, and (c) a follow up interview where they were asked to provide a hair sample for cortisol analyses. Data collection took place from 2018 to 2020., Results: PTSD severity moderated the relations between cortisol and days of drinking and binge drinking. In the context of high PTSD symptomology, women with high cortisol levels spent, on average, an additional 7.4 days drinking and 8.1 days binge drinking in the past 30 days compared to women with low cortisol levels, in a model adjusted for age., Conclusions: Results highlight the prominent role of PTSD symptoms in the association between cortisol and alcohol use among women experiencing IPV., Competing Interests: Declaration of Competing Interest No conflict declared., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To examine the effects of web neonatal intensive care unit diaries on the mental health, quality of life, sleep quality, care ability, and hormone levels of parents of preterm infants in the neonatal intensive care unit., Design: Prospective randomized controlled parallel-group clinical trial., Setting: Maternal and Child Health Hospital, Fujian, China., Methods: The control group received routine neonatal intensive care unit care, while the intervention group received a web neonatal intensive care unit diary based on routine care. Outcomes, including anxiety, depression, and post-traumatic stress disorder symptoms, quality of life, sleep quality, care ability, and cortisol and melatonin levels, were evaluated at T1 (Time 1, before the intervention), T2 (Time 2, immediately after the intervention), and T3 (Time 3, 1 month after the intervention)., Results: Seventy pairs of parents of preterm infants in the neonatal intensive care unit were randomly allocated to two groups: intervention (n = 35) and control (n = 35). The anxiety scores in the intervention group were significantly lower at T2 and T3 than those in the control group (P < 0.001). The care ability scores in the intervention group were significantly higher at T2 and T3 (P < 0.001). The prevalence of post-traumatic stress disorder at T3 was significantly different between the groups (P = 0.040). No significant differences were observed in the quality of life or sleep quality between the groups at T2 and T3 (P > 0.05). No significant differences were observed in cortisol and melatonin levels between the groups (P > 0.05)., Conclusions: Web neonatal intensive care unit diaries effectively relieved anxiety symptoms, reduced the prevalence of post-traumatic stress disorder, and enhanced the care abilities of parents of preterm infants in the neonatal intensive care unit., Implications for Clinical Practice: Web neonatal intensive care unit diary can be considered in clinical practice as a convenient psychological intervention method, especially among parents of preterm infants in the neonatal intensive care unit., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: Psychological stress can be a common risk factor for the development of oral and systemic disease; therefore, analysis of a pathophysiologic mechanisms that may explain this association may be significant in planning preventive strategies. The aim of this study was to investigate the association amongst academic stress, periodontal health, and salivary cortisol and nitrite and nitrate levels in a sample of university students., Methods: Participants (N = 14) were classified into 2 groups according to their exposure to academic stress due to periods of university exams (n = 6 and n = 8, respectively). All participants were subjected evlauted for their behavioural, psychological, and anthropometric parameters, as well as an oral health examination. A real-time polymerase chain reaction analysis in samples of saliva and plaque was used to detect Prevotella intermedia and Veillonella dispar as well as the total bacterial count. Nitrite/nitrate ratio (NR ratio) and cortisol in saliva were evaluated by enzyme-linked immunosorbent assay., Results: Full Mouth Bleeding Score, Full Mouth Plaque Score, and Gingival Index were significantly higher in the group exposed to academic stress. Nitrite was directly related to the presence of V dispar (coefficient, 0.13; P = .00; CI, 0.07 to 0.19) and inversely related to total bacterial count (coefficient, -0.07; P = .012; CI, -0.13 to 0.02). NR ratio was directly related to V dispar (coefficient, 4.35; P = .010; 95% CI, 1.35 to 7.36) and inversely related to total bacterial count (coefficient, -4.05; P = .018; 95% CI, -7.32 to 0.86)., Conclusions: These results confirm the importance of stress on periodontal health and salivary nitrite concentration and highlight a potential differential role of specific bacteria on nitrite concentration in saliva., Competing Interests: Conflict of interest None disclosed., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Electrochemical biosensors with high sensitivity can detect low concentrations of biomarkers, but their practical detection applications in complex biological environments such as human serum and sweat are severely limited by the biofouling. Herein, a conductive hydrogel based on bovine serum albumin (BSA) and conductive carbon black (CCB) was prepared for the construction of an antifouling biosensor. The BSA hydrogel (BSAG) was doped with CCB, and the prepared composite hydrogel exhibited good conductivity originated from the CCB and antifouling capability owing to the BSA hydrogel. An antifouling biosensor for the sensitive detection of cortisol was fabricated by drop-coating the conductive hydrogel onto a poly(3,4-ethylenedioxythiophene) (PEDOT) modified electrode and further immobilizing the cortisol aptamer. The constructed biosensor showed a linear range of 100 pg mL -1 - 10 μg mL -1 and a limit of detection of 26.0 pg mL -1 for the detection of cortisol, and it was capable of assaying cortisol accurately in complex human serum. This strategy of preparing antifouling and conductive hydrogels provides an effective way to develop robust electrochemical biosensors for biomarker detection in complex biological media., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Previous studies suggest that theta burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), applied to the left dorsolateral prefrontal cortex (DLPFC) might be a promising approach to modulate stress-reactive rumination and the associated psychophysiological stress response. Crucially, individuals showing higher levels of trait rumination might benefit more from prefrontal stimulation., Methods: In this sham-controlled study, 127 healthy individuals, with varying ruminative tendencies, received a single-session of intermittent TBS (iTBS), continuous TBS (cTBS) or sham TBS (sTBS) over the left DLPFC before being confronted with a Trier Social Stress Test., Results: Results showed significant TBS effects on salivary cortisol as a function of trait rumination. cTBS, as compared to sTBS and iTBS, resulted in an attenuated stress-induced cortisol response in high compared to low trait ruminators. Although independent of trait rumination levels, cTBS showed positive effects on stress-related changes in mood and, both cTBS and iTBS (versus sham) presented an enhanced heart rate recovery following the stressor. We found no evidence for (trait rumination-dependent) TBS effects on stress-reactive rumination, negative affect, subjective stress or heart rate variability., Conclusions: cTBS shows beneficial effects on certain measures of stress, especially in high trait ruminators., Significance: These findings highlight the importance of accounting for individual differences when examining TBS effects., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Mental health concerns are common among college students and more prevalent during examination periods when stress and anxiety are heightened. While the benefits of equine interaction have been reported, the impact of short-term equine interaction on coping skills valuable for managing test anxiety have yet to be studied. Therefore, the purpose of this preliminary study was to evaluate the impact of short-term equine interaction during the college examination period on development of coping skills and anxiety levels associated with testing, both self-reported and those reflected in physiological measures. Full-time college students engaged in a one-hour equine interaction session held on campus at the onset of final exam week. Participants completed a survey targeting perception of anxiety levels and coping skills. Heart rate and salivary cortisol measurements were collected pre- and post-session. Paired t-tests were performed between pre- and post- session measures and correlations between survey answers and physiological measures determined. Significant reductions were found in all areas of anxiety (Overall Academics P = 0.0003, Final Exam Preparation P = 0.0003, Taking Final Exam P = 0.0003). The reduction in exam-related anxiety was positively correlated to cortisol concentrations (r = 0.69, P = 0.03) with lower concentrations (P = 0.05) and increased heart rate (P = 0.003) post-session. Regarding coping skills, improvements were observed post-session in assertiveness (P = 0.008). Skill development coupled with reduced anxiety supports the potential benefits short-term equine interaction can offer students during the high stress periods, but these findings should be confirmed with more in-depth study., Competing Interests: Declaration of competing interest None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of the paper., (Copyright © 2024. Published by Elsevier Inc.)

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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: H. H. van Rossum; Owner and director of Huvaros B.v., Stock ownership and medical director of SelfSafeSure Blood Collection B.V. Has received (indirect) financial support from: Abbott, Beckman, Roche, Siemens, Sysmex, Health Holland and Stichting Treatmeds, M. Lanfermeijer; L.J. van Winden; D.E.J. Starreveld; S. Razab-Sekh; M. van Faassen; E.M.A. Bleiker: Have no known competing financial interest or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The ability of pigs to cope with routine farming practices can affect their welfare. This paper is part of a series on early experiences and stress, and reports on the effects of early human contact and housing on the responses of pigs to routine husbandry practices. Using a 2 × 2 factorial design, 48 litters of pigs were raised in either a conventional farrowing crate (FC) or a loose farrowing pen (LP; PigSAFE pen) which was larger, more physically complex and allowed the sow to move freely. Piglets were provided with either routine contact from stockpeople (C), or routine contact plus regular opportunities for positive human contact (+HC) involving 5 min of scratching, patting and stroking imposed to the litter 5 days/week from 0 to 4 weeks of age. At 4 weeks of age, piglets were weaned and re-housed with controlled mixing of litters within treatment. At 4 days of age, after only 3 bouts of the handling treatment, +HC pigs showed less escape behaviour than C pigs after capture by a stockperson for vaccinations and tail docking, and shorter durations of vocalisations throughout the procedures. The  +HC pigs also showed less escape behaviour when captured by a stockperson at 3 weeks of age. The FC pigs showed less escape behaviour than LP pigs after capture by a stockperson at 4 days of age but not at 3 weeks of age. Serum cortisol concentrations were lower in FC pigs than LP pigs 2 h after weaning but not at 49 h after weaning, whereas serum cortisol concentrations were lower in  +HC pigs than C pigs at 49 h after weaning but not at 2 h after weaning. In the period from 0 to 1 h after weaning, C pigs from LP performed the most escape attempts, although escape attempts were rare overall. When being moved out of the home pen by a stockperson at 21 weeks of age, FC pigs showed less baulking than LP pigs, but there were no detected effects of human contact treatment. In conclusion, both housing system and human contact during lactation affected the stress responses of pigs to routine husbandry practices. The +HC and FC pigs appeared to cope better than C and LP pigs, based on lower responses indicative of stress including escape behaviour, vocalisations and cortisol concentrations. These findings are consistent with corresponding reductions in fear that were reported in Part 1 of this series of papers., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The development of fear and stress responses in animals can be influenced by early life experiences, including interactions with humans, maternal care, and the physical surroundings. This paper is the first of three reporting on a large experiment examining the effects of the early housing environment and early positive human contact on stress resilience in pigs. This first paper reports on the responses of pigs to humans, novelty, and social isolation. Using a 2 × 2 factorial design, 48 litters of pigs were reared in either a conventional farrowing crate (FC) where the sow was confined or a loose farrowing pen (LP; PigSAFE pen) which was larger, more physically complex and allowed the sow to move freely throughout the farrowing and lactation period. Piglets were provided with either routine contact from stockpeople (C), or routine contact plus regular opportunities for positive human contact (+HC) involving 5 min of scratching, patting and stroking imposed to the litter 5 days/week from 0-4 weeks of age. The positive handling treatment was highly effective in reducing piglets' fear of humans, based on +HC piglets showing greater approach and less avoidance of an unfamiliar person at 3 weeks of age. There was evidence that this reduction in fear of humans lasted well beyond when the treatment was applied (lactation), with +HC pigs showing greater approach and less avoidance of humans in tests at 6, 9 and 14 weeks of age. The +HC treatment also reduced piglets' fear of a novel object at 3 weeks of age, and for pigs in FC, the cortisol response after social isolation at 7 weeks of age. Rearing in FC compared to LP reduced piglets' fear of novelty at 3 weeks of age, as well as their vocalisations and cortisol response to isolation at 7 weeks of age. The FC pigs showed greater approach and less avoidance of humans compared to LP pigs at 3, 4 and 6 weeks of age, but not at 9 and 14 weeks of age. These results show that positive handling early in life can reduce pigs' fear of humans, fear of novelty and physiological stress response to social isolation. The LP pigs were reared in a more isolated environment with less overall contact with stockpeople and other pigs, which may have increased their fear responses to humans and novel situations, suggesting that different housing systems can modulate these pigs' responses., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Early experiences can have long-term impacts on stress adaptability. This paper is the last of three in a series on early experiences and stress in pigs, and reports on the effects of early human contact and housing on the ability of pigs to cope with their general environment. Using a 2 × 2 factorial design, 48 litters of pigs were reared in either a farrowing crate (FC) or a loose farrowing pen (LP; PigSAFE pen) which was larger, more physically complex and allowed the sow to move freely. Piglets were provided with either routine contact from stockpeople (C), or routine contact plus regular opportunities for positive human contact (+HC) involving 5 min of scratching, patting and stroking imposed to the litter 5 days/week from 0 to 4 weeks of age. At 4 weeks of age (preweaning), C piglets that were reared in FC had considerably lower concentrations of serum brain-derived neurotrophic factor (BDNF) than piglets from the other treatment combinations. Compared to C pigs, +HC pigs had fewer injuries at 4 weeks of age. There were no clear effects of human contact on BDNF concentrations or injuries after weaning, or on basal cortisol or immunoglobulin-A concentrations, behavioural time budgets, tear staining, growth, or piglet survival. Compared to FC piglets, LP piglets showed more play behaviour and interactions with the dam and less repetitive nosing towards pen mates during lactation. There was no evidence that early housing affected pigs' behavioural time budgets or physiology after weaning. Tear staining severity was greater in LP piglets at 4 weeks of age, but this may have been associated with the higher growth rates of LP piglets preweaning. There was no effect of lactation housing on growth after weaning. Preweaning piglet mortality was higher in the loose system. The findings on BDNF concentrations, injuries and play behaviour suggest improved welfare during the treatment period in +HC and LP piglets compared to C and FC piglets, respectively. These results together with those from the other papers in this series indicate that positive human interaction early in life promotes stress adaptability in pigs. Furthermore, while the farrowing crate environment deprives piglets of opportunities for play behaviour and sow interaction, there was no evidence that rearing in crates negatively affected pig welfare or stress resilience after weaning. Whether these findings are specific to the two housing systems studied here, or can be generalised to other housing designs, warrants further research., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

24-hour urinary free cortisol (UFC) is considered as the first-line test for screening and diagnosis of Cushing's syndrome. Although 24-hour UFC assay has been extensively studied by liquid chromatography-tandem mass spectrometry (LC-MS/MS), an accurate assay coupled with a reliable sample preparation procedure and a method-specific reference interval would be very important for reasonable diagnosis. In this study, a simple dilute and shoot method has been proposed for UFC determination by LC-MS/MS. Namely, 50 µL of urine sample was mixed with 200 µL of a 50 % methanol/water solution containing the internal standard cortisol- 13 C3. The mixture was centrifuged and the supernatant was used for direct analysis by LC-MS/MS. This method was validated with wide linear range from 0.625 to 500 ng/ml with coefficients of variation (CVs) ≤ 3.64 %, excellent precision (intra-day CVs ≤ 5.70 % and inter-day CVs ≤ 5.33 %) and good recovery in the range of 93.3-109 %. The preservatives were further evaluated for urine storage. It was recommended that no preservatives could be used in collection of 24-hour urine for good detecting peaks. The investigation of reference interval and diagnostic performance finally confirmed the potential usage of this LC-MS/MS assay in routing clinical testing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

LC-MS is an indispensable tool for small molecule analysis in many fields; however, many small molecules require chemical derivatization to improve retention on commonly used reversed-phase columns and increase ionization. Benzoyl chloride (BzCl) derivatization is commonly used for derivatization of primary and secondary amines and phenolic alcohols, though evidence exists that with proper reaction conditions (i.e., specific bases), other hydroxyl groups may be derivatized too. Previous studies have examined BzCl concentration, reaction times, and reaction temperatures for derivatization of amines and phenols for LC-MS analysis; however, use of different bases, base concentration, and extending to conditions to hydroxyl groups for LC-MS analysis has not been well-studied. To address this understudied area and identify reaction conditions for both amino and hydroxyl groups, we performed a systematic study of reaction conditions on multiple classes of potential targets. For selected derivatization methods, detection limits and performance in a variety of biological matrices were assessed. Results highlight the importance of tailoring derivatization methods for a given application as they varied by molecule and/or molecule class. Compared to the standard BzCl method commonly used, alternative methods were identified to better derivatize challenging analytes (glucosamine, choline, cortisol, uridine, cytidine) with detection limits reaching 1100, 9, 38, 170, and 67 nM compared to undetectable, 170, 86, 1000, and 86 nM respectively. Sub-nanomolar detection limits were achieved for norepinephrine with alternative derivatization approaches. Improved derivatization methods for several classes and molecules including nucleosides, steroids, and molecules containing hydroxyl groups were also identified., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests Robert kennedy reports financial support was provided by National Institutes of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ashley Lenhart reports financial support was provided by the National Science Foundation, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Due to the COVID-19 pandemic, several associations worldwide have been recommending the use of 1% hydrogen peroxide solution as a preprocedural mouth rinse before dental treatments to reduce viral load in saliva. This protocol is also employed in stress studies, especially in the context of dental treatment that uses salivary biomarkers as an indicator. However, the effect of 1% hydrogen peroxide as mouth rinse on salivary biomarkers remains unclear., Objective: This study aims to investigate the effects of 1% hydrogen peroxide solution as a preprocedural mouth rinse on 3 salivary stress biomarkers-salivary cortisol, salivary secretory IgA, and salivary α-amylase-both on chemical influence and mechanical irrigation., Materials and Methods: Ninety healthy participants with confirmed negative Reverse Transcription Polymerase Chain Reaction results for COVID-19 at most 2 days prior to the experiment were included in this study. All participants were randomly allocated into 3 groups: experimental (1% hydrogen peroxide solution), positive control (distilled water), and negative control (no mouth rinse). Saliva samples were collected before and after mouth rinsing with the respective solutions. Salivary biomarkers were analysed using specific enzyme-linked immunosorbent assay kits., Results: Salivary cortisol and salivary α-amylase did not significantly differ before and after rinsing, whilst salivary sIgA levels decreased in all 3 groups. Nonetheless, there were no significant differences in the changes of these biomarkers across the 3 groups., Conclusions: This study shows that using 1% hydrogen peroxide solution as a preprocedural mouth rinse for universal precaution does not alter the levels of these 3 salivary biomarkers., Competing Interests: Conflict of interest None disclosed., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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, M age  = 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 (M T2  = 2.17, M T3  = 2.33) and HCC (M T2  = 4.79, M T3  = 9.56; pg/mg) increased over time, CRP did not (M T2  = 1.15, M T3  = 1.21; mg/L). Adjusted path models showed that technostress was negatively associated with HCC (β = -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 (β = 0.28, p =.001) and of HCC on CRP (β = -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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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 (R 2  > 0.97), except for testosterone (R 2  = 0.953) and metandrostenolon (R 2  = 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Automated immunoanalysis (AI) is an interesting alternative for measuring salivary cortisol, as the gold standard HPLC-MS/MS method is not yet readily available. The aim of this study was to evaluate the diagnostic performance of salivary cortisol immunoassay on the iSYS immunoanalyzer in adrenal dynamic tests. Cortisol was measured on iSYS and on HPLC-MS/MS in saliva samples collected after 1mg-dexamethasone suppression test (DST) in 115 patients suspected of Cushing syndrome, and during Synacthen® stimulation test (SST) in 108 patients suspected of adrenal insufficiency. Concentrations on AI correlated well with HPLC-MS/MS (Spearman r=0.9496; P<0.0001), but with a significant positive bias. ROC analysis of salivary cortisol identified optimal cut-off values on AI and HPLC-MS/MS of respectively 3.5 and 0.77nmol/L for DST and 32.6 and 13.8nmol/L at T60 after SST. Automated immunoassays for salivary cortisol are suitable in daily practice but require determination of specific cut-off and reference values., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Introduction: Although the concept of hope is highly relevant for cancer patients, little is known about its association with cancer-relevant biomarkers. Here we examined how hope was related to diurnal cortisol and interleukin-6 (IL-6), a pro-inflammatory cytokine previously associated with tumor biology and survival in ovarian cancer. Secondly, we examined whether hope and hopelessness are distinctly associated with these biomarkers., Method: Participants were 292 high-grade ovarian cancer patients who completed surveys and provided saliva samples 4x/daily for 3 days pre-surgery to assess diurnal cortisol. Blood (pre-surgery) and ascites were assessed for IL-6. Hope and hopelessness were assessed using standardized survey items from established scales (Center for Epidemiological Studies Depression Scale; Profile of Mood States, Functional Assessment of Cancer Therapy). Two hopeless items were z-scored and combined into a composite for analysis. Regression models related these variables to nocturnal cortisol, cortisol slope, plasma and ascites IL-6, adjusting for cancer stage, BMI, age, and depression., Results: Greater hope was significantly related to a steeper cortisol slope, β = -0.193, p = 0.046, and lower night cortisol, β = -0.227, p = 0.018, plasma IL-6, β = -0.142, p = 0.033, and ascites IL-6, β = -0.290, p = 0.002. Secondary analyses including both hope and hopelessness showed similar patterns, with distinct relationships of hope with significantly lower nocturnal cortisol β = -0.233,p = 0.017 and ascites IL-6, β = -0.282,p = 0.003, and between hopelessness and a flatter cortisol slope, β = 0.211, p = 0.031., Conclusions: These data suggest a biological signature of hope associated with less inflammation and more normalized diurnal cortisol in ovarian cancer. These findings have potential clinical utility but need replication with more diverse samples and validated assessments of hope., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Thaker has served as a consultant for Immunon, has been on advisory boards for Astra Zeneca, Clovis Oncology, Glaxo Smith Kline, Seagen, Agenus, Immunon, Immunogen, Mersana, Novocure R-Pharm, Zentalis, Aadi Pharmaceuticals, Merck, Caris, and Iovance Biotherapeutics, and has had research funding from Merck and Glaxo Smith Kline, and is a Immunon shareholder; Dr. Lutgendorf is an Abbvie shareholder; Dr. Sood has done consulting for Merck, Astra Zeneca, Kiyatec, Glaxo Smith Kline, Onexo, ImmunoGen, Iylon, has a patent planned/pending for EGFL6 antibody, and is a Biopath shareholder; Dr. Corn is the Chief Medical Officer of Lutris-Pharma. All other authors report no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Fish health can be affected by a multitude of stressors. Acute and chronic stress assessment via specific hormones monitoring has become a trending research topic. Common investigated matrices are blood and plasma, but recently less invasive substrates have been identified. As chemical composition of skin mucus/epidermis has been demonstrated to link with acute stress, and of scales with chronic stress in fish, the aim of the study was firstly to improve the determination of three stress hormones, namely cortisol (COL), cortisone (CON), and dehydroepiandrosterone-3-sulfate (DHEAS), in skin mucus/epidermis and scales of Aphanius fasciatus. Secondly, an evaluation of the impact of different environments on hormones concentrations was carried out. A liquid chromatography coupled to tandem mass spectrometry method (HPLC-MS/MS) and a preanalytical procedure were validated to determine COL, CON and DHEAS. This methodology was applied to compare a pull of field-collected fish with a pull of fish housed in the laboratory for one year. Our results highlighted a significant presence of cortisol and cortisone in epidermis of the latter pull (averagely 0.10 and 0.14 ng mg -1 , respectively), while in the first pull both hormones were much less concentrated (averagely 0.006 and 0.008 ng mg -1 , respectively). Scales of both pulls showed presence of hormones, with a higher concentration for fish housed in the laboratory, although a relevant difference in concentration was found only for cortisone. DHEAS was always below the limit of detection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Steroid hormones have been reported to be associated with endocrine system diseases. This paper proposes a novel procedure of deep eutectic solvent (DES)-assisted liquid-liquid extraction (LLE) to extract six steroid hormones (including cortisone, cortisol, androstenedione, testosterone, 17-hydroxyprogesterone, and progesterone) from serum coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of five types of L-proline, choline chloride, and citric acid-based DESs were tailored; the DES from L-proline and ethylene glycol at a molar ratio of 1:4 with 20 % acetonitrile was selected as the best-fit assisted solvent for the six steroid hormones compared with other DESs. The parameters for extraction by selected DES were optimized using Box-Behnken design (BBD), and the optimal extraction conditions are 200 µL of acetonitrile, 100 µL of the sample, and 80 µL of DES. Under optimum conditions, the method has good linear calibration ranges (between 0.07 ng mL -1 and 600 ng mL -1 ), correlation coefficients of determination (r 2 >0.99), and low limits of quantification (between 0.02 and 0.60 ng mL -1 ). The extraction recoveries were in the range of 81.84-114.43 %, and the intra-day and inter-day relative standard deviations (RSDs) were less than 10 %.In general, the DES-LC-MS/MS method is a simple and environmentally-friendly method, which can be complementary to the presently available methods for determining steroid hormones in serum., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Purpose: Stress and elevated maternal glycemia have negative effects on pregnancy. We evaluated the association of hair cortisol concentrations (HCC), a marker of chronic stress, with insulin resistance and gestational diabetes (GDM)., Methods: In total, 527 women from Lima, Peru, provided a hair sample in the second trimester of their pregnancy to measure HCC using liquid chromatography-tandem mass spectrometry. Each 6 cm of hair captured HCC in early (T1=1-12 weeks) and midpregnancy (T2 = 13-24 weeks). GDM diagnosis was conducted in midpregnancy. Multivariable regression models adjusted for putative risk factorsincluding maternal sociodemographic factors, diabetes history, and hair characteristics, were used to estimate the association of HCC with GDM and various glycemic traits., Results: GDM was diagnosed in 122 (23%) women. Mean HCC across pregnancy was T1 = 3.7 (±3.4) pg/mg and T2 = 4.8 (±3.4) pg/mg. HCC was associated with increased log-transformed units of fasting insulin (T1 = 0.15 [0.03, 0.27], T2 = 0.17 [0.04, 0.30]), homeostasis model assessment for insulin resistance (T1 = 0.14 [0.01, 0.26], T2 = 0.17 [0.03, 0.30]), and homeostasis model assessment for β-cell function (T1 = 0.20 [0.05, 0.34], T2 = 0.20 [0.04, 0.36]), but not with GDM (T1 = 0.95 [0.63, 1.40], T2 = 1.11 [0.74, 1.67])., Conclusions: Elevated maternal HCC was associated with abnormal insulin homeostasis in pregnancy. Dysregulation of the hypothalamic-pituitary-adrenal axis, as reflected by high HCC, may also contribute to insulin resistance syndrome in pregnancy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background & Aims: Maternal stress in the postpartum period affects not only the mother, but also her newborn child who is at increased risk for a wide range of disorders later in life. The mechanisms underlying transmission of maternal stress to the child remain elusive. Human milk (HM) is a potential candidate and is an important source of fatty acid (FA), which are crucial for child (neuro)development. This study aims to investigate whether maternal psychological and biological stress influences HM FA composition over the first month postpartum., Methods: The Amsterdam Mother's Milk study is a prospective cohort study. We included lactating women who delivered at term with a large range of stress levels: a high stress (HS) group, women whose child was hospitalized for a minimum of 2 days (n=23) and a control (CTL) group, women who gave birth to a healthy child (n=73). HM was collected three times a day at postpartum days 10, 17 and 24. Perceived psychological stress was measured using multiple validated questionnaires, while biological stress measures were based on cortisol in hair, saliva and HM. HM FAs were analyzed by gas-chromatography and compared between groups., Results: Maternal perceived stress scores were significantly higher in the HS group (p < 0.01), whereas cortisol measurements did not differ between groups. The absolute concentrations of total FA in HM (p=0.023), including the total amount of poly unsaturated fatty acids (PUFAs) (p=0.022) and omega-6 PUFAs (p=0.018), were lower in the HS group compared to the CTL group. Relative values of FAs did not differ between groups., Conclusion: Maternal stress in the first month postpartum was associated with overall lower levels of FA in HM. This possibly indicates a route of transmission of maternal stress signals to the infant. Future research should investigate if these stress-induced changes in HM FAs have consequences for child development., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Predicting viral suppression early is crucial to improving treatment outcomes among people living with HIV/AIDS (PLWH) in clinics. Viral suppression is affected by stress, making stress indicators a potential predictive factor. Most of previous studies used the self-report questionnaire as stress indicators, but there were great drawbacks due to its subjective. In contrast, end products of neuroendocrine systems such as hypothalamic-pituitaryadrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes and endogenous cannabinoid system (ECS) that involved in regulating stress as objective stress indicators are urgently needed to predict viral suppression. Therefore, this study aimed to investigate whether neuroendocrine indictors can strongly predict viral suppression among PLWH in China., Methods: This cross-sectional study recruited 1198 PLWH on antiretroviral therapy (ART) in Guangxi, China. The concentrations of steroids (i.e., cortisol, cortisone, dehydroepiandrosterone, testosterone and progesterone) and endocannabinoids (i.e., N-arachidonoyl-ethanolamine and 1-arachidonyl glycerol) in hair were quantitated using the LC-APCI + -MS/MS method. To screen biomarkers that were used to predict viral suppression, association between hair biomarkers and viral suppression was examined by Mann-Whitney U test and partial correlation analyses. Receiver operating characteristic (ROC) curves and binary logistic regression based on the optimal classification threshold determined with ROC curves were used to estimate the prediction effects of the screened biomarkers on viral suppression (HIV-1 RNA < 200 copies/mL)., Results: Hair levels of dehydroepiandrosterone (DHEA), and N-arachidonoyl-ethanolamine (AEA), and the cortisol to DHEA ratio exhibited significant intergroup differences (ps < 0.05) and were correlated with HIV viral load (ps < 0.05). Hair DHEA concentrations strongly predicted viral suppression, showing good classification performance (area under the ROC curve = 0.651, p < 0.01) and strong predictive utility (adjusted odd ratio = 2.324, 95 % confidence interval = 1.211-4.899, p < 0.05) with an optimal threshold of 10.5 pg/mg. A hair AEA concentration of 2.4 pg/mg was the optimal threshold for predicting viral suppression based on good classification performance (area under the ROC curve = 0.598, p < 0.05) and predictive power (adjusted odd ratio = 2.124, 95 % confidence interval = 1.045-4.244, p < 0.05). In hair levels of cortisol to DHEA, viral suppression was observed to be highly predictive, with a threshold of 10.5 pg/mg being optimal for classification (area under the ROC curve = 0.624, p < 0.05) and prediction (adjusted odd ratio = 0.421, 95 % confidence interval = 0.201-0.785, p < 0.05)., Conclusion: Hair levels of DHEA, and AEA and the cortisol to DHEA ratio were screened and verified to have significant predictive power with optimal thresholds for predicting viral suppression in a large-scale cohort. The data may provide new insights into predictors of successful virological outcomes and inform public health intervention and clinical practice to assist PLWH in achieving and sustaining viral suppression., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Prenatal air pollutant exposure has been linked to impaired fetal growth. However, its special vulnerability windows and biological mechanisms remain unclear. A prospective birth cohort study including 7419 mother-newborn pairs was conducted from 2015 to 2020 to determine critical exposure windows and examine whether cortisol mediates the relationship between air pollutant exposure and fetal growth. Air pollutant data for PM 2.5 , PM 10 , SO 2 , and CO were obtained from the Hefei City Ecology and Environment Bureau. Data on fetal ultrasound measurements and birth size were collected. Maternal and cord blood samples were used for measuring cortisol. Prenatal air pollutant (PM 2.5 , PM 10 , SO 2 , and CO) exposure, particularly in the first trimester, was associated with reduced fetal size from later pregnancy to birth. An IQR increase in PM 2.5 (β = 0.082, 95%CI: 0.029, 0.135), PM 10 (β = 0.086, 95%CI: 0.036, 0.136), SO 2 (β = 0.086, 95%CI: 0.028, 0.144), and CO (β = 0.063, 95%CI: 0.017, 0.109) exposure in the first trimester was associated with higher cord blood cortisol levels. Significant relationships were observed between air pollutant exposure in the first trimester and increased ratio of cord to maternal blood cortisol levels. Exposure to high levels of cord blood cortisol significantly reduced the Z scores of birth weight (β = -0.17, 95%CI: -0.23, -0.10), length (β = -0.09, 95%CI: -0.16, -0.03), and head circumference (β = -0.33, 95%CI: -0.42, -0.25). Mediation analysis showed that the association of air pollutant exposure in the first trimester with neonatal parameters mediated by cord blood cortisol was 20.62%. These results indicated that air pollutant exposure during pregnancy could reduce fetal growth by the increased fetal cortisol levels due to placental barrier impairment, with the critical window of exposure occurring in the first trimester., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Acute pancreatitis (AP) ranges in severity from mild to severe with high mortality. Severe AP, similar to other critical illnesses, is associated with changes in cortisol level. Early increase of high-sensitivity C-reactive protein (hs-CRP) as an inflammatory marker could be an indicator of AP progression. We aimed to assess the level of cortisol and hs-CRP on initial diagnosis of AP and identify their prognostic value., Methods: This case-control study included patients with AP and a control group of healthy subjects. Laboratory tests such as liver profile, kidney functions, blood picture, lactate dehydrogenase, blood glucose, and lipogram were evaluated, the severity of AP was determined, the duration of hospitalization, complications, and outcomes were identified, and the serum levels of cortisol and hs-CRP were assessed., Results: There were 90 patients with AP and 60 controls with a higher percent of females in both groups. Serum cortisol and hs-CRP were significantly higher in AP relative to controls and were higher in severe AP relative to mild AP. Significant positive correlation was present between high cortisol and severity of AP (r = 0.520 and p<0.001) and negatively with pancreatic necrosis (r= - 0.303 and p = 0.007) and morality (r= - 0.432, p = 0.005) while hs-CRP did not show significant correlation., Conclusions: Different levels of serum cortisol in early AP should be considered on initial diagnosis. High cortisol level was a good prognostic indicator for AP with low mortality. This could have further implications on the appropriate initiation of steroid therapy to prevent necrotizing pancreatitis and lower the mortality. Meanwhile, hs-CRP has a low prognostic value in early AP., Competing Interests: Declaration of Competing Interest Authors declare no conflicts of interest., (Copyright © 2021 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

We have developed a powerful biosensing strategy for immobilizing histidine-tagged (His-Tag)-oriented recombinant nano-protein immobilization on a chemically modified glassy carbon electrode (GCE) surfaces via (S)-N-(5-amino-1-carboxypentyl)iminodiacetic acid (ANTA) acting as a chelating Ni 2+ centered interaction. Here, we introduce a label-free electro-sensor to quantify cortisol levels in saliva samples for point-of-care testing (POCT). The high specificity of the chemically modified GCE was established by genetically bio-engineered metal-binding sites on the selected recombinant apoferritin (R-AFTN) nano-protein to impart functionality to its surface and by coating the carbon surface with the self-assembled monolayers of 4-aminobenzoic acid (4-ABA) attached to ANTA groups complexed with Ni 2+ transition metal ions. Despite the variety of conventional assays available to monitor cortisol levels, they require bulky exterior outfits, which hinders use in the healthcare systems. Therefore, we performed a rapid, easy-to-implement, and low-cost quantitative electro-sensor to enable the real-time detection of cortisol levels in saliva samples. As a result, the cortisol electro-sensor fabricated with high specificity utilizing a GCE could measure cortisol levels with a detection limit of 0.95 ng/ml and sensitivity of 7.91 μA/(ng/mL), which is a practical approach in human saliva. Thus, protein nanoprobe-based cortisol biosensing showed high sensitivity and selectivity for the direct electro-sensing of cortisol for POCT., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Hair cortisol concentration (HCC) is used as an indicator of long-term stress or pathologies in humans and increasingly in animals. Although the main mechanism for the incorporation of cortisol into the hair shaft is by diffusion from blood, cortisol may also be incorporated from external sources by contamination of the hair surface. In farm animals under conventional husbandry conditions and trapped animals, contamination of hair with cortisol-containing body fluids, especially with urine, was shown to be a considerable confounding factor when studying HCCs. We recently found that cattle and pigs exhibit elevated HCCs in distal hair segments and assume that the incorporation of external cortisol is facilitated in these older hair segments. Therefore, the aim of this study was to investigate the effects of urine contamination on HCC in different hair segments of pigs and cattle, and to determine whether different cleaning protocols can prevent contamination effects. In an in vivo experiment in pigs (n = 18) and an in vitro experiment in cattle (n = 12), hairs were repeatedly contaminated with urine of the respective species and then shaved or cut in segments. Cortisol concentrations in hair segments were analysed by enzyme immunoassay after washing with isopropanol and extraction with methanol. Results were compared with HCCs in untreated hairs or hairs treated with water. Moreover, additional bovine hair samples contaminated with urine were subjected to two further cleaning procedures. Contamination with urine generally increased HCCs, and it was demonstrated for the first time that this effect is more pronounced in distal compared to proximal hair segments in both species. The immersion of bovine hair in vitro in water caused a washout of cortisol, which was also more pronounced in distal hair segments. In general, the different cleaning protocols for cattle hair did not prevent contamination effects, so we assume that external cortisol not only adheres but is incorporated into the hair shaft. Structural damage of older, distal hair segments may facilitate permeability of the hair matrix and diffusion of cortisol from and into aqueous solutions. Thus, the validity of HCC as a marker of stress is compromised in animals where soiling of hair with body fluids is a risk factor. Therefore, hair samples should be collected from clean body regions and, if possible, using proximal hair segments., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Maternal hypothalamic-pituitary-adrenal (HPA) axis disruption in pregnancy may contribute to the programming of childhood respiratory disease and may modify the effect of chemical toxins, like lead (Pb), on lung development. Child sex may further modify these effects. We sought to prospectively examine associations between maternal HPA axis disruption, prenatal Pb and childhood lung function and explore potential effect modification by maternal cortisol and child sex on the association between prenatal Pb and lung function outcomes., Materials and Methods: Analyses included 222 mothers and children enrolled in a longitudinal birth cohort study in Mexico City. Maternal diurnal salivary cortisol was assessed in pregnancy; cortisol awakening response (CAR) and diurnal slope were calculated. Blood Pb was measured during the second trimester of pregnancy. Post-bronchodilator lung function was tested at ages 8-11 years. Associations were modeled using generalized linear models with interaction terms, adjusting for covariates., Results: A higher (flatter) diurnal slope was associated with lower FEV 1 /FVC ratio (β: 0.433, 95%CI [-0.766, -0.101]). We did not find any main effect associations between prenatal Pb and lung function outcomes. We report an interaction between Pb and cortisol in relation to FEV 1 /FVC and FEF 25-75% (p interaction <0.05 for all). Higher prenatal Pb was associated with reduced FEV 1 /FVC only in children whose mothers had a high CAR. Higher prenatal Pb was also associated with reduced FEV 1 /FVC and FEF 25-75% in mothers with a flatter diurnal slope. A 3-way interaction between prenatal Pb, CAR and sex on FEV 1 /FVC, indicated that boys born to women with high CAR and higher prenatal Pb levels had lower FEV 1 /FVC ratios (p interaction  = 0.067)., Conclusions: Associations between prenatal Pb and childhood lung function were modified by disrupted maternal cortisol in pregnancy and child sex. These findings underscore the need to consider complex interactions to fully elucidate effects of prenatal Pb exposure on childhood lung function., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Studies have shown that increased maternal cortisol level is associated with child adverse health outcomes. Hair cortisol (HC) is suitable for assessing long-term circulating cortisol concentration. Only two previous studies reported beneficial associations between cortisol and residential greenness during pregnancy and no study focused on the first trimester. Our aim was to evaluate the association between residential greenness and first trimester HC levels among pregnant women in Israel., Methods: Women were recruited during second and third trimesters. Hair samples were collected from the scalp and retrospective HC levels during the first trimester were quantified for 217 women. HC levels were natural log transformed and outliers were excluded. Based on geocoded birth address, small area sociodemographic status (SES) and mean residential surrounding greenness were calculated using high-resolution satellite-based Normalised Difference Vegetation Index (NDVI) data at 100, 300 and 500-m buffers in a cross-sectional approach. In addition, longitudinal exposure to mean greenness during a week preconception and during the first trimester were calculated. Missing covariates were imputed and linearity of the associations were evaluated. Generalized linear models were used to estimate the crude and adjusted associations controlled for the relevant covariates., Results: After exclusion of outliers, for 211 women, crude and adjusted beneficial associations between exposure to higher mean NDVI and HC levels were observed for all the exposure measures. An increase in 1 interquartile range of greenness (100 m buffer) was associated with a statistically significant lower estimated natural log mean HC level (-0.27 95% CI: -0.44; -0.11). The associations were robust to adjustment for covariates. The findings were consistent for different buffers, for the longitudinal approach, when all observations were included in the analysis and slightly stronger associations were observed for women with addresses geocoded at the home or street level. For most of the exposure measures, stronger associations were observed among those of lower sociodemographic status., Conclusion: Our findings that more greenness associated with reduced maternal cortisol levels measured in the hair during the first trimester, could have substantial implications for urban planners and public health professional. If our observations will be replicated, it may present a useful avenue for public-health intervention to promote health through the provision of greenness exposure during early pregnancy, specifically to disadvantage populations., (Copyright © 2021. Published by Elsevier Inc.)

Cortisol and cortisone are common markers for stress and thus preferentially analyzed in matrices that allow non-invasive sampling such as saliva. Though the major drawback of immunoassays is lack of specificity due to cross reactivities, they are still most commonly used for quantification of steroid hormones. To overcome such problems, sensitive methods based on liquid chromatography-mass spectrometry are becoming more and more accepted as the golden standard for steroid bioanalysis as they achieve accurate quantification at trace levels for multiple analytes in the same run. Along this line, the aim of this study was the development of a new microflow UHPLC-ESI-MS/MS method for the measurement of salivary cortisol and cortisone, which due to its microflow regime provides enhanced sensitivity and is more ecofriendly. The developed method implemented sample preparation by Solid-Phase Extraction (SPE) in a 96-well plate format. Data acquisitions were carried out in MRM (multiple reaction monitoring) mode. The quantitative determination of endogenous compounds in saliva remains a challenge since analyte-free matrix is lacking. Hence, a surrogate calibrant approach with cortisol-d 4 andcortisone- 13 C 3 was applied for the target compounds in the presented method. A number of factors were optimized and the method validated. The lower limit of quantitation (LLOQ) was 72 and 62 pg mL -1 for cortisol and cortisone, respectively. Linear calibration was achieved in the range from 0.062 to 75.5 ng mL -1 for cortisol-d 4 and 0.072 to 44 ng mL -1 forcortisone- 13 C 3 . The performance of the method was also evaluated via proficiency test for salivary cortisol. Finally, it was applied successfully to evaluate cortisol and cortisone concentrations in multiple batches in routine clinical stress study samples (4056 total injections with 1983 study samples). Moreover, the instrument performance (in particular retention time variability) within each batch, between different batches and lot-to-lot of 5 investigated capillary columns over time is described. The work documents that micro-UHPLC-ESI-MS/MS is suitable and robust enough to carry out a full clinical study with greater than 1000s of samples over an extended period if adequate internal standards can be used., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A modification of magnetic-based solvent-assisted dispersive solid-phase extraction (M-SA-DSPE) has been employed for the determination of the biomarkers cortisol and cortisone in saliva samples. M-SA-DSPE is based on the dispersion of the sorbent material by using a disperser solvent like in dispersive solid phase extraction (SA-DSPE) but a magnetic sorbent is used like in magnetic dispersive solid-phase extraction (M-DSPE). Thus, the magnetic sorbent containing the target analytes is retrieved using an external magnet like in M-DSPE. Finally, the analytes are desorbed into a small volume of organic solvent for the subsequent chromatographic analysis. To this regard, a M-SA-DSPE-based method was developed using a magnetic composite as sorbent, made of CoFe 2 O 4 magnetic nanoparticles embedded into a reversed phase polymer (Strata-X TM -RP), which exhibits affinity to the target analytes. Then, liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was used to measure both analytes in the M-SA-DSPE extract. Under the optimized conditions, good analytical features were obtained: limits of detection of 0.029 ng mL -1 for cortisol and 0.018 ng mL -1 for cortisone, repeatability (as RSD) ≤ 10 %, and relative recoveries between 86 and 111 %, showing no significant matrix effects. Finally, the proposed method was applied to the analysis of saliva from different volunteers. This new methodology allows a fast and non-invasive determination of cortisol and cortisone, and it employs small amounts of sample, organic solvent and sorbent. Likewise, the sample treatment is minimum, since any supporting equipment (vortex, centrifuge, ultrasounds, etc.) is required., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A novel extraction method was developed for the determination of cortisol and cortisone. In this study, we prepared a hydrophobic deep eutectic solvent (DES) by mixing trioctylmethylammonium chloride and pentafluorophenol as a hydrogen bond acceptor and a hydrogen bond donor, respectively, for use as the extraction solvent. The extraction of cortisol and cortisone was performed by adding a small volume of the DES to the aqueous sample. After centrifugation, the resulting sedimented DES phase was injected into a reversed-phase liquid chroamtography column, and the analytes were detected with an ultraviolet detector at 254 nm. Under the optimized extraction conditions, the enrichment factors of cortisol and cortisone were 9.3 and 8.5, respectively. Furthermore, the linear dynamic ranges were established over a concentration range of 10-200 pmol mL -1 (r 2  > 0.9992), and the limits of detection of cortisol and cortisone were found to be 2.1 and 1.8 pmol mL -1 , respectively. The applicability of this method was evaluated by analyzing the cortisol and cortisone contents of human saliva samples., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Prenatal stress is known to influence fetal hypothalamic-pituitary-adrenal axis (HPA axis) development. Placental 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) is a central gene in this pathway, but little is known about what influences its functioning. We assess how maternal distress influences HSD11B2 functioning, and how HSD11B2 in turn, is associated with infant HPA axis development., Methods: Data come from 24 mother-infant dyads on the Galápagos Islands. Using adjusted linear regression models, we assess the effects of maternal psychosocial (stress and depressive symptoms, measured by the Perceived Stress Scale and the Patient Health Questionnaire-8, respectively) and physiological (HPA axis dysregulation) distress during pregnancy on HSD11B2 methylation and expression and then test how these HSD11B2 measures influence infant HPA axis development., Results: Maternal HPA axis dysregulation during pregnancy is associated with lower placental HSD11B2 expression, which is associated with an exaggerated cortisol reactivity in infants. Sex-specific analyses revealed that maternal depressive symptoms may influence the functioning of placental HSD11B2 differently in girls (n = 11, 46%) than in boys (n = 13, 54%), though the sample size was small., Discussion: These results support a disrupted adaptive framework, in which the ability to upregulate HSD11B2 expression in response to acute stress diminishes as maternal stress becomes chronic. In this model, chronic stress may exhaust the protective mechanism of HSD11B2, leaving the infant vulnerable to high levels of maternal cortisol, which could injure the fetal HPA axis and disrupt long-term neurobehavioral and metabolic development. While larger studies will be needed to confirm these findings, this study offers exploratory results on the effects of maternal distress on both HSD11B2 methylation and expression and the effect of HSD11B2 on offspring HPA axis development., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Leukocyte glucocorticoid sensitivity (GCS) pertains to the responsivity of leukocytes to the regulating actions of glucocorticoids, such as cortisol. Impaired endocrine regulation may link the metabolic syndrome (MetS) to the development of cardiovascular disease. We tested if the physiological association between endogenous cortisol levels and peripheral leukocyte composition becomes disrupted in individuals with MetS., Methods: MetS was assessed among 689 German industrial employees. The covariance between cortisol levels and hematologic parameters (i.e., proportions of neutrophils and lymphocytes) and their ratio was explored, which has been proposed as a proxy for GCS in vivo. Cortisol level before blood collection was assessed by repeated saliva collection, and the area under the curve was calculated. Linear regression models were adjusted for potential confounders including age, gender, BMI, income, and lifestyle factors., Results: Cortisol levels did not differ between subgroups. Participants without MetS (n = 552) showed the expected association of cortisol with hematologic parameters (β = 0.207 to 0.216; p values < 0.001). No association (β = 0.078 to 0.083; p values > 0.10) was found among those with MetS (n = 137), consistent with a reduced GCS. Analyses of separate MetS components showed that reduced GCS was associated specifically with decreased high-density lipoprotein and elevated fasting plasma glucose., Conclusions: Utilizing a novel statistical approach to infer GCS, this study provided first epidemiological evidence of aberrant physiological regulation of leukocyte distribution by endogenous cortisol levels among individuals with MetS. These findings underline the idea that MetS may involve disruption of endocrine-immune regulation., (Copyright © 2020 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Due to the variable clinical features and its rarity diagnosis of Cushing's disease (CD) is often delayed. Clearly, awareness for CD needs to be raised, accompanied by the availability of simple and accurate screening tests. Late-night salivary cortisol (LNSC), 1 mg dexamethasone suppression test (DST), and urinary free cortisol (UFC) have all been extensively studied, demonstrating high sensitivity and specificity for the diagnosis of Cushing's syndrome. However, each of those well-established tests has its own distinctive features, making it preferable in specific clinical conditions and patient groups. To choose the most appropriate test in individual patients, an expert endocrinologist should be consulted. This review will discuss the pitfalls for each of those tests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Incidentally discovered adrenal masses are common and mostly benign and non-functioning adenomas. However, evolving evidence suggests that a notable proportion of these adrenal adenomas may demonstrate mild autonomous cortisol secretion (MACS), which has been associated with an increased risk for hypertension, hyperglycemia, obesity, dyslipidemia, vertebral fractures, adverse cardiovascular events, and mortality. Therefore, it is advised that all patients with an incidentally discovered adrenal mass be tested for MACS. When there is convincing evidence for MACS, surgical adrenalectomy has been associated with an improvement in certain metabolic parameters and a reduction in vertebral fractures; however, conclusive evidence demonstrating decreased cardiovascular outcomes or mortality are not yet available. Future studies with adequate randomization and follow-up to assess adverse clinical endpoints are needed to determine the optimal management and follow-up of patients with MACS., Competing Interests: Declaration of competing interest AV reports consulting fees from HRA Pharma, Corcept Therapeutics, and Mineralys., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Previous research on the association between testosterone (T) and immunity has produced conflicting results., Objectives: We address two potential reasons for these empirical inconsistencies in the present research. First, the association between T and immunity may depend on which branch of the immune system is considered. Here, we examine secretory IgA (sIgA), a measure of mucosal immunity functionally related to respiratory infection risk. Second, the association between T and immunity may depend on a third regulatory variable. Therefore, we examine the interaction between T and cortisol (CORT) as well as their independent and combined effects on mucosal immunity. To do this, we explore intra-individual associations between sIgA, CORT, and T within a single day (i.e., morning vs. evening) and across 2 sequential mornings. We target two samples of men: (1) cisgender (i.e., born and identifying as men), and (2) transgender (i.e., born female but identifying as men) undergoing T therapy for gender realignment., Materials and Methods: One hundred and forty-eight adult men (transgender n = 29) provided saliva samples at three time points: (1) upon waking, (2) before sleep on the same day, and (3) upon waking the following day. Samples were assayed in duplicate for sIgA, T and CORT., Results: For cisgender men, sIgA, T, and CORT exhibited clear circadian rhythms and were significantly related within and between samples. For transgender men, evidence for circadian change was found for sIgA and CORT, but not T. Further, sIgA was associated with CORT, but not T., Discussion and Conclusions: This study provides the first evidence that salivary T and sIgA concentrations are associated within a single day and across sequential days for cisgender men. Differences between cis- and transgender men suggest that this may only be true for T levels driven by endogenous production; however, future studies should employ a larger sample size., (Copyright © 2020. Published by Elsevier Inc.)

Non-ionic surfactants such as polysorbates, known as Tween™ 20 and Tween™ 80, are routinely used within the healthcare and pharmaceutical industry to enhance solubility. This work focuses on analysing the two aforementioned polysorbates, each considered at three purity levels with four model compounds, across the critical micellar concentration (CMC) range for each surfactant. Such data is of interest to investigate the influence of micelle formation upon compound-polysorbate interaction. Two analytical techniques were utilised, namely spectroscopic solubility determination and micellar liquid chromatography (MLC). In all cases it was apparent that the maximum solubility for all four compounds increased substantially at concentrations greater than the CMC and that, in most cases, a different retention profile was observed using MLC once the CMC had been exceeded. This paper is the first to have used such techniques to investigate the behaviour of these polysorbates over a series of concentrations and three levels of polysorbate purity. The findings indicate that the solubilisation potential of polysorbates differs once the CMC has been surpassed and is dependent upon the level of purity selected, i.e. compound-surfactant interactions are partially a consequence of the presence of micelles rather than monomer as well as polysorbate purity. Thus, formulators should include such polysorbates at optimised concentrations and purity if they wish to maximise their solubilisation potential., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Objectives: According to some studies, a putatively calming effect of EEG neurofeedback training could be useful as a therapeutic tool in psychiatric practice. With the aim of elucidating this possibility, we tested the efficacy of a single session of ↑sensorimotor (SMR)/↓theta neurofeedback training for mood improvement in 32 healthy men, taking into account trainability, independence and interpretability of the results., Methods: A pre-post design, with the following dependent variables, was applied: (i) psychometric measures of mood with regards to anxiety, depression, and anger (Profile of Mood State, POMS, and State Trait Anxiety Inventory, STAI); (ii) biological measures (salivary levels of cortisol); (iii) neurophysiological measures (EEG frequency band power analysis). In accordance with general recommendations for research in neurofeedback, a control group receiving sham neurofeedback was included., Results: Anxiety levels decreased after the real neurofeedback and increased after the sham neurofeedback (P<0.01, size effect 0.9 for comparison between groups). Cortisol decreased after the experiment in both groups, though with significantly more pronounced effects in the desired direction after the real neurofeedback (P<0.04; size effect 0.7). The group receiving real neurofeedback significantly enhanced their SMR band (P<0.004; size effect 0.88), without changes in the theta band. The group receiving sham neurofeedback did not show any EEG changes., Conclusions: The improvement observed in anxiety was greater in the experimental group than in the sham group, confirmed by both subjective (psychometric) measures and objective (biological) measures. This was demonstrated to be associated with the real neurofeedback, though a nonspecific (placebo) effect likely also contributed., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: Exposure to adverse childhood experiences (ACEs) may lead to stress-induced upregulation of inflammatory and neuroendocrine processes. However, it remains unclear whether such effects persist into later life, and which dimensions of ACEs might have the strongest impact on these biological mechanisms. Therefore, this study investigated the effects of ACEs on C-reactive protein (CRP) and hair cortisol in a large sample of older adults, distinguishing between cumulative exposure and dimensions of ACEs., Methods: We utilised data from the English Longitudinal Study of Ageing. ACEs were assessed through retrospective reports at wave 3(2006/07). CRP (N = 4198) was measured at waves 4(2008/09) and 6(2012/13), and hair cortisol (N = 3357) at wave 6. The effects of ACEs cumulative exposure were examined using linear and ordinal logistic regression analysis. ACEs dimensions (i.e. threat, household dysfunction, low parental bonding, and loss of an attachment figure) were identified using explorative and confirmatory factor analysis with cross-validation. All analyses were adjusted for relevant confounders., Results: Participants with three or more ACEs had higher CRP levels at wave 4 and an elevated risk of high CRP concentrations across waves 4 and 6 compared with those who did not experience any ACEs. The four ACEs dimensions were all positively associated with both CRP outcomes and had similar effect sizes. In contrast, neither the cumulative score nor the dimensions of ACEs were significantly related to hair cortisol. However, there was a positive, yet small, interaction effect between ACEs and age on hair cortisol., Conclusion: Older adults who retrospectively reported three or more ACEs had chronically elevated CRP levels and exhibited a slightly steeper increase in hair cortisol with age. Different dimensions of ACEs had similar associations with the biomarkers., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Experiencing childhood adversity has been associated with significant changes in inflammation, cell-mediated immunocompetence, and cortisol secretion. Relatively few studies have examined, longitudinally, alterations to inflammatory processes during adolescence, especially outside Western contexts; none have evaluated biomarker trajectories for at-risk youth in response to a structured behavioral intervention. We conducted a randomized controlled trial evaluating the efficacy of a humanitarian intervention targeting stress-alleviation, with 12-18 year-old Syrian refugees (n = 446) and Jordanian non-refugees (n = 371) living side-by-side in war-affected communities in Jordan. We measured C-reactive protein (CRP), Epstein-Barr virus antibodies (EBV), and hair cortisol concentration (HCC) at three timepoints (pre/post intervention and 11 month follow-up), and assessed three main outcomes (psychosocial stress, mental health, and cognitive function). Using growth mixture models, regressions, and growth curve models, we identified three distinct trajectories for CRP, two for EBV, and three for HCC, and examined their associations with age, gender, BMI, poverty, and trauma. We found associations with BMI for CRP, refugee status for EBV, and BMI and gender with HCC trajectory. In terms of health outcomes, we found associations between rising CRP levels and perceived stress (B =  -2.92, p = .007), and between HCC hypersecretion and insecurity (B = 7.21, p = .017). In terms of responses to the intervention, we observed no differential impacts by CRP or EBV trajectories, unlike HCC. These results suggest that commonly-assayed biomarkers do not associate with health outcomes and respond to targeted interventions in straightforward ways. Our study is the first to examine multiple biomarker trajectories in war-affected adolescents, in order to better evaluate the extent, timing, and malleability of the biological signatures of poverty, conflict, and forced displacement., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

In routine hormonology, liquid chromatography mass spectrometry (LCMS) is now an established technique for androgen, urinary cortisol and metanephrine assay. It has the undeniable advantage of great analytical specificity, but with sensitivity that clearly depends on financial investment in a very high-end spectrometer. We describe the general principles of LCMS and the routine applications so far developed in hormonology. The purpose is to familiarise endocrinologists with the techniques under development and their pros and cons., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)