Consistently increased dorsolateral prefrontal cortex activity during the exposure to acute stressors.

Stress has a major impact on our mental health. Nonetheless, it is still not fully understood how the human brain responds to ongoing stressful events. Here, we aimed to determine the cortical dynamics during the exposure to ecologically valid, standardized stressors. To this end, we conducted 3 experiments in which healthy participants underwent the Trier Social Stress Test (experiments 1 and 2) and the Socially Evaluated Cold Pressor Test (experiment 3) or a respective control manipulation, while we measured their cortical activity using functional near-infrared spectroscopy. Increases in salivary cortisol and subjective stress levels confirmed the successful stress induction in all experiments. Results of experiment 1 showed significantly increased cortical activity, in particular in the dorsolateral prefrontal cortex, during the exposure to the Trier Social Stress Test. Experiment 2 replicated this finding and showed further that this stress-related increase in dorsolateral prefrontal cortex activity was transient and limited to the period of the Trier Social Stress Test. Experiment 3 demonstrated the increased dorsolateral prefrontal cortex activity during the Socially Evaluated Cold Pressor Test, suggesting that this increase is generalizable and not specific to the Trier Social Stress Test. Together, these data show consistently that dorsolateral prefrontal cortex activity is not reduced, as commonly assumed, but increased under stress, which may promote coping with the ongoing stressor.

Interplay of Adolescents' and Parents' Mindsets of Socioeconomic Status on Adolescents' Stress-Related Outcomes.

The reciprocity and variation of values and beliefs are dynamic features of the parent-child relationship. Parents and adolescents may hold congruent or incongruent views regarding the malleability of socioeconomic status (mindset of SES), potentially influencing adolescents' psychological and physiological stress outcomes, as reflected in stress perceptions and the hypothalamic-pituitary-adrenal (HPA) axis functioning. The current study investigated how patterns of parent-adolescent congruence and incongruence in mindset of SES were associated with adolescents' perceived stress and diurnal cortisol patterns four months later. A total of 253 adolescents (Mage = 12.60, 46.2% girls) and their parents (Mage = 40.09 years, 59.5% mothers) participated in this study. Polynomial regression analyses and response surface analyses showed that adolescents perceived lower levels of stress when they themselves or their parents reported a stronger growth mindset of SES. Additionally, adolescents with a stronger growth mindset of SES also exhibited a steeper diurnal cortisol slope. Moreover, parents' mindset significantly interacted with adolescents' mindset to influence adolescents' diurnal cortisol patterns such that when adolescents hold weaker growth mindset of SES, those with higher parental growth mindsets had significantly higher cortisol awakening response and steeper diurnal cortisol slope. Furthermore, adolescents who showed incongruence with their parents but had averagely stronger growth mindsets of SES reported a significantly steeper diurnal cortisol slope than those who had averagely weaker growth mindsets with their parents. The findings point to the beneficial impacts of the growth mindset of SES on stress-related outcomes among adolescents, as well as the significance of considering both parents' and adolescents' mindsets when exploring these associations.

Machine learning-based detection of acute psychosocial stress from body posture and movements.

Investigating acute stress responses is crucial to understanding the underlying mechanisms of stress. Current stress assessment methods include self-reports that can be biased and biomarkers that are often based on complex laboratory procedures. A promising additional modality for stress assessment might be the observation of body movements, which are affected by negative emotions and threatening situations. In this paper, we investigated the relationship between acute psychosocial stress induction and body posture and movements. We collected motion data from N = 59 individuals over two studies (Pilot Study: N = 20, Main Study: N = 39) using inertial measurement unit (IMU)-based motion capture suits. In both studies, individuals underwent the Trier Social Stress Test (TSST) and a stress-free control condition (friendly-TSST; f-TSST) in randomized order. Our results show that acute stress induction leads to a reproducible freezing behavior, characterized by less overall motion as well as more and longer periods of no movement. Based on these data, we trained machine learning pipelines to detect acute stress solely from movement information, achieving an accuracy of 75.0 ± 17.7 % (Pilot Study) and 73.4 ± 7.7 % (Main Study). This, for the first time, suggests that body posture and movements can be used to detect whether individuals are exposed to acute psychosocial stress. While more studies are needed to further validate our approach, we are convinced that motion information can be a valuable extension to the existing biomarkers and can help to obtain a more holistic picture of the human stress response. Our work is the first to systematically explore the use of full-body body posture and movement to gain novel insights into the human stress response and its effects on the body and mind.

Energy Expenditure, a New Tool for Monitoring Surgical Stress in Colorectal Oncological Patients: A Prospective, Monocentric Study.

BACKGROUND: Surgical stress response in colorectal surgery consists of a neurohormonal and an immunological response and influences oncological outcomes. The intensity of surgical trauma influences mortality, morbidity, and metastasis' occurrence in colorectal neoplasia. Energy expenditure (EE) stands for the body's energy consumed to keep its homeostasis and can be either calculated or measured by direct or indirect calorimetry. AIM: The present study attempted to evaluate surgical stress response using EE measurement and compare it to the postoperative cortisol dynamic. METHODS: A prospective, monocentric study was conducted over a period of one year in the Anesthesiology Department including 21 patients from whom serum cortisol values were collected in the preoperative period and on the first postoperative day, and EE was measured and recorded every 15 minutes throughout surgery using the indirect calorimetry method. The study compared EE values' dynamic registered 30 minutes after intubation and 30 minutes before extubating (after abdominal closure) to cortisol perioperative dynamic. RESULTS: We enrolled 21 patients and 84 measurements were recorded, 42 probes of serum cortisol and 42 measurements of EE. The mean value of the first measurement of serum cortisol was 13.60±3.6 µg and the second was 16.21±6.52 µg. The average value of the first EE recording was 1273.9±278 kcal and 1463.4±398.2 kcal of the second recording. The bivariate analysis performed showed a good correlation between cortisol variation and EE's variation (Spearman coefficient=0.666, p<0.001, CI=0.285, 0.865). In nine cases (42.85%), cortisol value at 24 hours reached the baseline or below the baselines preoperative value. In eight cases (38.09%), patients' EE at the end of the surgery was lower than that recorded at the beginning of the surgery. CONCLUSIONS: Intraoperative EE variation correlated well with cortisol perioperative dynamic and stood out in this study as a valuable and accessible predictor of surgical stress in colorectal surgery.

Hair cortisol levels are associated with overweight and obesity in the ELSA-Brasil cohort.

Introduction: Hair cortisol level has recently been identified as a promising marker for detecting long-term cortisol levels and a marker of hypothalamic-pituitary-adrenal cortex (HPA) axis activity. However, research on the association between obesity and an altered cortisol metabolism remains controversial. Objective: This study aimed to investigate the relationship between hair cortisol levels and overweight and obesity in participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Methods: This was a cross-sectional study involving 2,499 participants from the second follow-up (visit 3, 2017-2019) attending research centers in Rio de Janeiro and Rio Grande do Sul states. Hair samples were collected, and cortisol levels were analyzed using enzyme-linked immunosorbent assay (ELISA) kits. Cortisol levels were classified as low (< 40 pg/mg), medium (40-128 pg/mg), or high (> 128 pg/mg). The participants were classified as eutrophic, overweight, or obese according to their weight (kg) and height (m2). Odds ratios (ORs) with 95% confidence intervals (95%CI) were estimated. Results: Of the 2499 individuals, 30% had eutrophic weight, 40% were overweight, and 30% were obese. Notably, cortisol levels gradually increased with increasing body weight. Among participants with high hair cortisol levels, 41.2% were classified as overweight and 34.2% as obese. Multinomial logistic regression analysis indicated that participants with high cortisol levels were 43% (OR =1.43; 95%CI: 1.02-2.03) more likely to be overweight and 72% (OR =1.72; 95%CI:1.20-2.47) more likely to be obese than participants with low hair cortisol levels. After adjustment for all covariates, high cortisol levels remained associated with obesity (OR = 1.54; 95%CI:1.02-2.31) and overweight (OR =1.33; 95%CI:0.91-1.94). Conclusion: In the ELSA-Brazil cohort, hair stress were positively associated with overweight and obesity. These results underscore the importance of considering stress and cortisol as potential factors in obesity prevention and intervention efforts, and highlight a novel aspect of the complex relationship between stress and obesity in the Brazilian population.

Hair cortisol stability after 5-year storage: Insights from a sample of 17-year-old adolescents.

Background: Hair has become an increasingly valuable medium to investigate the association between chronic stress, stable differences in systemic cortisol secretion and later health. Assessing cortisol in hair has many advantages, notably its non-invasive and retrospective nature, the need for a single biospecimen and convenient storage until analysis. However, few studies offered empirical evidence documenting the long-term temporal stability of hair cortisol concentration (HCC) prior to analysis, especially in humans. Yet, knowing how long hair samples can be stored without compromising the accuracy of cortisol measurement is of crucial importance when planning data collection and analysis. This study examined the stability of HCC in hair samples assayed twice, five years apart. Methods: We randomly selected from a larger distribution of HCC measured in 17-year-old participants 39 hair samples to be reanalyzed five years later, under the same general conditions. Samples were assayed in duplicate using a luminescence immunoassay and compared with the original HCC using the Lin's concordance correlation coefficient (CCC), Bland-Altman plot analysis and Wilcoxon rank test. Results: Findings indicated a good concordance and temporal stability between the two samples assayed five years apart (CCC [95% confidence interval] = 0.84 [0.72-0.91]), although a small decrease in HCC was noted 5 years later (8.4% reduction, p = 0.001). Conclusion: Our study confirms that hair samples, when stored at room temperature and away from sunlight, can be assayed for at least five years without risking a loss of precision in HCC measurement.

Hair hormone data from Syrian refugee children: Perspectives from a two-year longitudinal study.

For numerous issues of convenience and acceptability, hair hormone data have been increasingly incorporated in the field of war trauma and forced displacement, allowing retrospective examination of several biological metrics thought to covary with refugees' mental health. As a relatively new research method, however, there remain several complexities and uncertainties surrounding the use of hair hormones, from initial hair sampling to final statistical analysis, many of which are underappreciated in the extant literature, and restrict the potential utility of hair hormones. To promote awareness, we provide a narrative overview of our experiences collecting and analyzing hair hormone data in a large cohort of Syrian refugee children (n = 1594), across two sampling waves spaced 12 months apart. We highlight both the challenges faced, and the promising results obtained thus far, and draw comparisons to other prominent studies in this field. Recommendations are provided to future researchers, with emphasis on longitudinal study designs, thorough collection and reporting of hair-related variables, and careful adherence to current laboratory guidelines and practices.

Comparative analysis of salivary cortisol measurements using different assay methods in relation to serum-free cortisol measurement.

Objectives: Salivary cortisol reflects the biologically active form of serum cortisol, offering a noninvasive evaluation method for the diurnal rhythm of the hypothalamic-pituitary-adrenal (HPA) axis. While liquid chromatography-tandem mass spectrometry (LC-MS/MS) is known for its specificity, immunoassays (IA) are commonly used because of their simplicity. This study aimed to assess the performance of salivary cortisol measurement using both IA and LC-MS/MS in comparison to serum-free cortisol measurement. Methods: Assay results for 188 saliva and 94 serum samples from 47 participants were analyzed. Salivary samples collected at different time points were analyzed using IA and LC-MS/MS. Serum samples were analyzed for cortisol, cortisol-binding globulin, and free cortisol. The statistical analyses included correlations and method comparisons. Results: The diurnal salivary cortisol profiles exhibited a comparable circadian rhythm pattern; however, the concentrations measured using IA were consistently higher than those measured using LC-MS/MS. The correlation analysis revealed robust associations among salivary cortisol (IA), salivary cortisol (LC-MS/MS), and serum-free cortisol levels (LC-MS/MS). However, the method comparison revealed a systematic bias between IA and LC-MS/MS in salivary cortisol measurement. Conclusions: This study contributes to the ongoing debate on assay techniques by affirming the suitability of IA and LC-MS/MS for salivary cortisol measurement to assess dynamic changes in HPA axis activity. The identified systematic bias emphasizes the importance of selecting methods based on specific research or clinical requirements.

Perceived Stress, Salivary Cortisol, and Temperament Traits among Students of Dental Medicine: A Prospective and Interventional Study.

Academic stress affects students' psychological and physiological well-being. Dental undergraduate programs are known for their demanding curriculum, leading to significant stress symptoms. The objective was to determine if salivary cortisol levels were higher in students exposed to academic stress, assess the relationship between stress severity/temperament and cortisol values, and explore relaxation technique effects. Salivary cortisol was measured at two time points for all participants: Before exams and during a relaxation period after summer break. A third measurement was conducted for students with high pre-test cortisol levels who received instructions on progressive muscle relaxation (PMR) before subsequent exams. Additionally, participants completed two questionnaires: Perceived Stress Scale (PSS) and Fisher's Temperament Questionnaire. The group analysis based on the PSS indicated that 39 participants reported high stress. Women demonstrated significantly higher stress than men (p = 0.042054). A significant difference in stress levels was observed between director and builder temperament types (p = 0.029276). Cortisol levels showed a significant decrease from the first measurement to the second measurement, and the third measurement after implementing PMR. The grade in the "Dermatovenereology" course correlated with stress level according to the PSS (k = 0.578467). Pre-test cortisol levels correlated with the frequency of using PMR guidelines during winter test periods (k = 0.416138). Stress negatively affects the immune system and poses health risks. Implementing stress reduction techniques in dental/medical education could benefit students and the healthcare system.

The Influence of Noise Level on the Stress Response of Hospitalized Cats.

The study aimed to investigate the impact of noise levels in the hospital environment on the stress experienced by hospitalized cats undergoing elective ovariohysterectomy surgery. A total of 33 domestic female cats were included in the study, divided into four groups: a control group (CG) and three experimental groups based on ward noise levels: G1 (Quiet, <60 dB), G2 (Medium, between 60 and 85 dB), and G3 (Noisy, >85 dB). Behavioral assessments, respiratory rate (RR), and plasma cortisol levels ([Cort]p) were measured as indicators of stress. A composite measure of stress, termed the final stress value (FSV), was calculated by summing scores across various behavioral categories. Data collection occurred at three time points: immediately following surgery (T1), and at 2 h (T2) and 3 h (T3) post-surgery. FSV and RR were assessed at all three time points (T1, T2, and T3), while [Cort]p levels were measured at T1 and T3. The study observed that the median values of FSV, RR, and [Cort]p tended to increase with both higher noise levels and longer exposure durations to noise. Significant differences in RR were found between group pairs G1G2 at T1 (|D| = 0.63 < cut-off = 0.98), and G2G3 at T2 (|D| = 0.69 < cut-off = 0.97). Regarding [Cort]p, significant differences were noted between the CGG1 group pair at T0 (p < 0.01), and T3 (p = 0.03). Furthermore, an excellent Spearman correlation coefficient (rho = 0.91) was found between FSV and RR, indicating that RR can serve as an effective tool for assessing stress levels in cats. The findings of this study provide valuable insights into the welfare of cats in a hospital environment and support the scientific validity of existing recommendations aimed at improving their well-being. Specifically, the study underscores the importance of minimizing noise levels in hospitals as a means to reduce stress in cats. This conclusion aligns with existing guidelines and recommendations for enhancing the welfare of hospitalized cats.

Impact of mindfulness versus supportive sex education on stress in women with sexual interest/arousal disorder.

Low desire in women is the most common sexual difficulty, and stress has been identified as a significant predictor of symptoms. We evaluated a mindfulness-based cognitive therapy (MBCT) group treatment versus a sex education comparison group treatment (STEP) on self-reported stress and on the physiological stress response measured via morning-to-evening cortisol slope in 148 women with a diagnosis of sexual interest/arousal disorder (SIAD). Perceived stress decreased following treatment in both groups, and significantly more after MBCT. The cortisol slope was steeper (indicative of better stress system regulation) from pre-treatment to 6-month follow-up, with no differences between the groups. As an exploratory analysis, we found that the reduction in perceived stress predicted increases in sexual desire and decreases in sex-related distress for participants after MBCT only. These findings suggest that group mindfulness targeting women with low sexual desire leads to improvements in self-reported and physiological stress, with improvements in self-reported stress partially accounting for improvements in sexual desire and distress.

Wearable Sensing Device Integrated with Prestored Reagents for Cortisol Detection in Sweat.

Wearable sweat sensors have achieved rapid development since they hold great potential in personalized health monitoring. However, a typical difficulty in practical processes is the control of working conditions for biorecognition elements, e.g., pH level and ionic strength in sweat may decrease the affinity between analytes and recognition elements. Here, we developed a wearable sensing device for cortisol detection in sweat using an aptamer as the recognition element. The device integrated functions of sweat collection, reagent prestorage, and signal conversion. Especially, the components of prestored reagents were optimized according to the inherent characteristics of sweat samples and electrodes, which allowed us to keep optimal conditions for aptamers. The sweat samples were transferred from the inlet of the device to the reagent prestored chamber, and the dry preserved reagents were rehydrated with sweat and then arrived at the aptamer-modified electrodes. Sweat samples of volunteers were analyzed by the wearable sensing device, and the results showed a good correlation with those of the ELISA kit. We believe that this convenient and reliable wearable sensing device has significant potential in self-health monitoring.

A dilute and shoot method for urinary free cortisol analysis by LC-MS/MS.

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-13C3. 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.

High-risk pregnancy and its relationship with the neurodevelopment and behavior of 2-year-old children.

High-risk pregnancies elevate maternal stress, impacting offspring neurodevelopment and behavior. This study, involving 112 participants, aimed to compare perceived stress, neurodevelopment, and behavior in high-risk and low-risk pregnancies. Two groups, high-risk and low-risk, were assessed during pregnancy for stress using hair cortisol and psychological analysis. At 24 months post-birth, their children's neurodevelopment and behavior were evaluated. Results revealed higher perceived stress and pregnancy-related concerns in high-risk pregnancies, contrasting with low-risk pregnancies. Offspring from high-risk pregnancies displayed elevated internalizing behavior scores, while low-risk pregnancies showed higher externalizing behavior scores. Additionally, women in low-risk pregnancies exhibited increased cortisol concentrations 24 months post-delivery. These findings underscore the necessity for early stress detection and prevention programs during pregnancy, particularly in high-risk cases, to enhance maternal and infant health.

Drug development and potential targets for Cushing's syndrome.

Cushing's syndrome (CS) is a complex disorder characterized by the excessive secretion of cortisol, with Cushing's disease (CD), particularly associated with pituitary tumors, exhibiting heightened morbidity and mortality. Although transsphenoidal pituitary surgery (TSS) stands as the primary treatment for CD, there is a crucial need to optimize patient prognosis. Current medical therapy serves as an adjunctive measure due to its unsatisfactory efficacy and unpredictable side effects. In this comprehensive review, we delve into recent advances in understanding the pathogenesis of CS and explore therapeutic options by conducting a critical analysis of potential drug targets and candidates. Additionally, we provide an overview of the design strategy employed in previously reported candidates, along with a summary of structure-activity relationship (SAR) analyses and their biological efficacy. This review aims to contribute valuable insights to the evolving landscape of CS research, shedding light on potential avenues for therapeutic development.

Association of seasonal changes in circulating cortisol concentrations with the expression of cortisol biosynthetic enzymes and a glucocorticoid receptor in the blubber of common bottlenose dolphin.

Cortisol is secreted from the adrenal cortex in response to stress, and its circulating levels are used as robust physiological indicators of stress intensity in various animals. Cortisol is also produced locally in adipose tissue by the conversion of steroid hormones such as cortisone, which is related to fat accumulation. Circulating cortisol levels, probably induced by cold stress, increase in cetaceans under cold conditions. However, whether cortisol production in subcutaneous adipose tissue is enhanced when fat accumulation is renewed during the cold season remains unclear. Therefore, in this study, we examine the effect of environmental temperature on the expression of cortisol synthesis-related enzymes and a glucocorticoid receptor in the subcutaneous fat (blubber) and explore the association between these expressions and fluctuations in circulating cortisol levels in common bottlenose dolphins (Tursiops truncatus). Skin biopsies were obtained seasonally from eight female dolphins, and seasonal differences in the expression of target genes in the blubber were analyzed. Blood samples were collected throughout the year, and cortisol levels were measured. We found that the expressions of cytochrome P450 family 21 subfamily A member 2 (CYP21A2) and nuclear receptor subfamily 3 group C member 1 (NR3C1), a glucocorticoid receptor, were increased in the cold season, and 11 beta-hydroxysteroid dehydrogenase type 1 (HSD11B1) showed a similar trend. Blood cortisol levels increased when the water temperature decreased. These results suggest that the conversion of 17-hydroxyprogesterone to cortisol via 11-deoxycortisol and/or of cortisone to cortisol is enhanced under cold conditions, and the physiological effects of cortisol in subcutaneous adipose tissue may contribute to on-site lipid accumulation and increase the circulating cortisol concentrations. The results obtained in this study highlight the role of cortisol in the regulation of the blubber that has developed to adapt to aquatic life.

Age-related increase in the expression of 11ß-hydroxysteroid dehydrogenase type 1 in the hippocampus of male rhesus macaques.

Introduction: The hippocampus is especially susceptible to age-associated neuronal pathologies, and there is concern that the age-associated rise in cortisol secretion from the adrenal gland may contribute to their etiology. Furthermore, because 11ß-hydroxysteroid dehydrogenase type 1 (HSD11B1) catalyzes the reduction of cortisone to the active hormone cortisol, it is plausible that an increase in the expression of this enzyme enhances the deleterious impact of cortisol in the hippocampus and contributes to the neuronal pathologies that underlie cognitive decline in the elderly. Methods: Rhesus macaques were used as a translational animal model of human aging, to examine age-related changes in gene and protein expressions of (HSD11B1/HSD11B1) in the hippocampus, a region of the brain that plays a crucial role in learning and memory. Results: Older animals showed significantly (p < 0.01) higher base-line cortisol levels in the circulation. In addition, they showed significantly (p < 0.05) higher hippocampal expression of HSD11B1 but not NR3C1 and NR3C2 (i.e., two receptor-encoding genes through which cortisol exerts its physiological actions). A similar age-related significant (p < 0.05) increase in the expression of the HSD11B1 was revealed at the protein level by western blot analysis. Discussion: The data suggest that an age-related increase in the expression of hippocampal HSD11B1 is likely to raise cortisol concentrations in this cognitive brain area, and thereby contribute to the etiology of neuropathologies that ultimately lead to neuronal loss and dementia. Targeting this enzyme pharmacologically may help to reduce the negative impact of elevated cortisol concentrations within glucocorticoid-sensitive brain areas and thereby afford neuronal protection.

Refugee health and physiological profiles in transitional settlements in Serbia and Kenya: Comparative evidence for effects of gender and social support.

When armed conflict compels people to flee from their homelands, they embark on protracted journeys during which they experience wide ranging physical, social, and psychological challenges. Few studies have focused on refugee psychosocial and physiological profiles during the transitional phase of forced migration that often involves temporary sheltering. Transient refugees' experiences can vary substantially based on local socio-ecological conditions in temporary settlements, including the length of stay, living conditions, as well as the availability and accessibility of physical and social resources. In this study, we compared physiological and psychosocial data from refugees (N=365; 406 observations) in Serbia and Kenya, respectively, with divergent temporal (length of stay) and socio-ecological conditions. In Serbia, refugees resided in asylum centers (mean stay: 0.9 y); in Kenya they were living in Kakuma Refugee Camp (mean stay: 8.8 y), one of the world's largest camps at the time. We had limited ability to directly compare psychosocial measures and used meta-analytic techniques to evaluate predictors of refugee mental and physical health at the two sites, including based on perceived social support. Refugees in Serbia had higher fingernail cortisol (p < 0.001) and were less likely to have elevated C-reactive protein (CRP) levels (p < 0.01) than refugees in Kakuma. We found common gender differences in both settings; women had lower cortisol but higher EBV antibody titers and higher likelihood of having elevated CRP compared to men (all p < 0.01). Woman also reported poorer mental and physical health (p < 0.001). These physiological and health differences may reflect variation between men and women in their psychosocial and physical experiences of factors such as stress, violence, and trauma during their journeys and as transitional refugees. Finally, we also found that refugees with lower levels of perceived social support reported poorer physical and mental health (p < 0.001). Although our results are cross-sectional, they suggest that this intermittent phase of the refugee experience is a key window for helping enhance refugee well-being through an emphasis on interpersonal and community support systems.

Steroids-producing nodules: a two-layered adrenocortical nodular structure as a precursor lesion of cortisol-producing adenoma.

BACKGROUND: The human adrenal cortex consists of three functionally and structurally distinct layers; zona glomerulosa, zona fasciculata (zF), and zona reticularis (zR), and produces adrenal steroid hormones in a layer-specific manner; aldosterone, cortisol, and adrenal androgens, respectively. Cortisol-producing adenomas (CPAs) occur mostly as a result of somatic mutations associated with the protein kinase A pathway. However, how CPAs develop after adrenocortical cells acquire genetic mutations, remains poorly understood. METHODS: We conducted integrated approaches combining the detailed histopathologic studies with genetic, RNA-sequencing, and spatially resolved transcriptome (SRT) analyses for the adrenal cortices adjacent to human adrenocortical tumours. FINDINGS: Histopathological analysis revealed an adrenocortical nodular structure that exhibits the two-layered zF- and zR-like structure. The nodular structures harbour GNAS somatic mutations, known as a driver mutation of CPAs, and confer cell proliferative and autonomous steroidogenic capacities, which we termed steroids-producing nodules (SPNs). RNA-sequencing coupled with SRT analysis suggests that the expansion of the zF-like structure contributes to the formation of CPAs, whereas the zR-like structure is characterised by a macrophage-mediated immune response. INTERPRETATION: We postulate that CPAs arise from a precursor lesion, SPNs, where two distinct cell populations might contribute differently to adrenocortical tumorigenesis. Our data also provide clues to the molecular mechanisms underlying the layered structures of human adrenocortical tissues. FUNDING: KAKENHI, The Uehara Memorial Foundation, Daiwa Securities Health Foundation, Kaibara Morikazu Medical Science Promotion Foundation, Secom Science and Technology Foundation, ONO Medical Research Foundation, and Japan Foundation for Applied Enzymology.

Alterations of Whole-Body Glucose Metabolism in a Feline SARS-CoV-2 Infection Model.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been especially devastating to patients with comorbidities, including metabolic and cardiovascular diseases. Elevated blood glucose during SARS-CoV-2 infection increased mortality of COVID-19 patients, although the mechanisms are not well understood. It has been previously demonstrated that glucose transport and utilization is a crucial pathway for other highly infectious RNA viruses. Thus, we hypothesized that SARS-CoV-2 infection could lead to alterations in cellular and whole-body glucose metabolism. Specific pathogen free domestic cats were intratracheally inoculated with USA-WA1/2020 (Wild-type) SARS-CoV-2 or vehicle-inoculated, then sacrificed at 4- and 8-days post-inoculation (dpi). Blood glucose and cortisol concentrations were elevated at 4 and 8 dpi. Blood ketones, insulin, and angiotensin 2 concentrations remained unchanged throughout the experimental timeline. SARS-CoV-2 RNA was detected in the lung and heart, without changes in angiotensin converting enzyme 2 (ACE2) RNA expression. In the lung, SARS-CoV-2 infection increased glucose transporter 1 (GLUT1) protein level at 4 and 8 dpi., while GLUT4 level was only upregulated at 8 dpi. In the heart, GLUT-1 and -4 protein levels remained unchanged. Furthermore, GLUT1 level was upregulated in the skeletal muscle at 8 dpi, and AMPK was activated in the heart of infected cats. SARS-CoV-2 infection increased blood glucose concentration and pulmonary GLUT protein levels. These findings suggest that SARS-CoV-2 infection induces metabolic reprogramming primarily in the lung to support viral replication. Furthermore, this translational feline model mimicked human COVID-19 and could be used to explore novel therapeutic targets to treat metabolic disease during SARS-CoV-2 infection.