The effect of a synthetic analog of kisspeptin 1, a peptide involved in the regulation of the hypothalamicpituitary- gonadal (HPG) stress axis, on the cortisol level of Danio rerio fish was investigated. Kisspeptin 1 was administered at doses of 2 μg/kg and 8 μg/kg followed by resting for 1 h and 4 h. We found that kisspeptin at doses of 2 μg/kg and 8 μg/kg increased cortisol levels, with a significant spike in cortisol levels at 1 h post-injection.

Background and Objectives: Temporomandibular disorders or dysfunction (TMDs) encompass a range of complex conditions that impact the temporomandibular joint (TMJ), chewing muscles, teeth, and/or their supporting tissues. Stress is one of the most associated factors studied as a TMD predictor. The aim is to figure out the influence of stress on TMJ status and salivary cortisol in university students during and before exams. Materials and Methods: The study was non-experimental, employing a longitudinal, analytical, observational cohort design. The study population consisted of students enrolled in the physiotherapy degree program at the Alfonso X El Sabio University (Madrid, Spain). Data were collected during two distinct academic periods: the first period was characterized by low academic stress and no exams, and the second period coincided with the high academic stress of final course exams. The collected results included sociodemographic data, assessment of TMJ status (Fonseca Index), evaluation of muscle evaluation (masseter, upper trapezius, and sternocleidomastoid) using a MOXY Monitor (muscle oxygenation) and Neurotrac® (surface EMG, sEMG), assessment of perceived stress (PSS-14), and measurement of salivary cortisol (enzyme immunoassay with Elisa). The statistical analysis was conducted with a confidence level of 95% (p ≤ 0.05) and asymptotic or bilateral significance. Results: 70 students were analyzed during two different measurement periods. According to the Fonseca Index, initially, 37.14% of the analyzed students showed mild TMDs, 17.14% moderate TMDs, and 45.72% showed no TMDs. In general terms, stress increased with age and is related to female sex, maximum mouth opening decreased with age, oxygen saturation decreased with age and academic stress, and myoglobin concentration was related to age. Furthermore, muscle contraction decreased during higher academic stress and increased with age. For women, age was a risk factor for suffering from TMDs, and stress worsened the transition from having TMDs to having no TMDs in both sexes. Conclusions: Academic stress influences TMJ status and muscle outcomes such as oxygen saturation, myoglobin concentration, and muscle contraction, although more research is needed.

Genetic variation among inhaled corticosteroid (ICS)-metabolizing enzymes may affect asthma control, but evidence is limited. This study tested the hypothesis that single-nucleotide polymorphisms (SNPs) in Cytochrome P450 3A5 (CYP3A5) would affect asthma outcomes. Patients aged 2-18 years with persistent asthma were recruited to use the electronic AsthmaTracker (e-AT), a self-monitoring tool that records weekly asthma control, medication use, and asthma outcomes. A subset of patients provided saliva samples for SNP analysis and participated in a pharmacokinetic study. Multivariable regression analysis adjusted for age, sex, race, and ethnicity was used to evaluate the impact of CYP3A5 SNPs on asthma outcomes, including asthma control (measured using the asthma symptom tracker, a modified version of the asthma control test or ACT), exacerbations, and hospital admissions. Plasma corticosteroid and cortisol concentrations post-ICS dosing were also assayed using liquid chromatography-tandem mass spectrometry. Of the 751 patients using the e-AT, 166 (22.1%) provided saliva samples and 16 completed the PK study. The e-AT cohort was 65.1% male, and 89.6% White, 6.0% Native Hawaiian, 1.2% Black, 1.2% Native American, 1.8% of unknown race, and 15.7% Hispanic/Latino; the median age was 8.35 (IQR: 5.51-11.3) years. CYP3A5*3/*3 frequency was 75.8% in White subjects, 50% in Native Hawaiians and 76.9% in Hispanic/Latino subjects. Compared with CYP3A5*3/*3, the CYP3A5*1/*x genotype was associated with reduced weekly asthma control (OR: 0.98; 95% CI: 0.97-0.98; p < 0.001), increased exacerbations (OR: 6.43; 95% CI: 4.56-9.07; p < 0.001), and increased asthma hospitalizations (OR: 1.66; 95% CI: 1.43-1.93; p < 0.001); analysis of 3/*3, *1/*1 and *1/*3 separately showed an allelic copy effect. Finally, PK analysis post-ICS dosing suggested muted changes in cortisol concentrations for patients with the CYP3A5*3/*3 genotype, as opposed to an effect on ICS PK. Detection of CYP3A5*3/3, CYPA35*1/*3, and CYP3A5*1/*1 could impact inhaled steroid treatment strategies for asthma in the future.

Hypoxia is a globally pressing environmental problem in aquatic ecosystems. In the present study, a comprehensive analysis was performed to evaluate the effects of hypoxia on physiological responses (hematology, cortisol, biochemistry, hif gene expression and the HIF pathway) of hybrid sturgeons (Acipenser schrenckii ♂ × Acipenser baerii ♀). A total of 180 hybrid sturgeon adults were exposed to dissolved oxygen (DO) levels of 7.00 ± 0.2 mg/L (control, N), 3.5 ± 0.2 mg/L (moderate hypoxia, MH) or 1.00 ± 0.1 mg/L (severe hypoxia, SH) and were sampled at 1 h, 6 h and 24 h after hypoxia. The results showed that the red blood cell (RBC) counts and the hemoglobin (HGB) concentration were significantly increased 6 h and 24 h after hypoxia in the SH group. The serum cortisol concentrations gradually increased with the decrease in the DO levels. Moreover, several serum biochemical parameters (AST, AKP, HBDB, LDH, GLU, TP and T-Bil) were significantly altered at 24 h in the SH group. The HIFs are transcription activators that function as master regulators in hypoxia. In this study, a complete set of six hif genes were identified and characterized in hybrid sturgeon for the first time. After hypoxia, five out of six sturgeon hif genes were significantly differentially expressed in gills, especially hif-1α and hif-3α, with more than 20-fold changes, suggesting their important roles in adaptation to hypoxia in hybrid sturgeon. A meta-analysis indicated that the HIF pathway, a major pathway for adaptation to hypoxic environments, was activated in the liver of the hybrid sturgeon 24 h after the hypoxia challenge. Our study demonstrated that hypoxia, particularly severe hypoxia (1.00 ± 0.1 mg/L), could cause considerable stress for the hybrid sturgeon. These results shed light on their adaptive mechanisms and potential biomarkers for hypoxia tolerance, aiding in aquaculture and conservation efforts.

We prepared a supramolecular hydrogel composed of decanoic acid and arginine (C10/Arg gel) and evaluated its application to a transdermal formulation. C10/Arg gel adjusted to pH 7 with 1 M NaOH aq or 1 M HCl aq provided a translucent hydrogel with a lamellar liquid crystal structure in the concentration region of decanoic acid ≥12% and arginine ≤9%. Rheological measurements showed that C10/Arg gel is a viscoelastic material with both solid and liquid properties, with elasticity being dominant over viscosity in the low shear stress region. The skin permeability of hydrocortisone (HC) and indomethacin (IM) from C10/Arg gels was investigated in vitro using hairless mouse skin and compared to control formulation drug suspensions (IM or HC) in water. The cumulative permeation amount of HC and IM from the C10/Arg gel at 10 h after application was approximately 16 and 11 times higher than that of the control, respectively. On the other hand, the flux of IM decreased with increasing arginine concentration, likely due to the acid-base interaction between Arg and IM in C10/Arg gel. Adequate drug skin permeation enhancement by C10/Arg gel requires optimizing the gel composition for each specific drug.

Maternal depression is a risk factor for future mental health problems in offspring, with stress-system function as a candidate vulnerability factor. Here we present initial validation of an online matching-task (MT) paradigm in young children exposed to maternal depression (N = 40), a first in stressor-paradigm research for this age group. Investigations of stress-system reactivity that can be conducted online are an innovative assessment approach, accelerated by the COVID-19 pandemic. Results indicate high feasibility, with a >75% data collection success rate across measures, similar-to or better-than in-person success rates in young children. Overall, the online MT elicited significant heart rate but not cortisol reactivity. Individual differences in child mental health symptoms were a moderator of reactivity to the stressor such that children with lower, but not higher, behavioral problems exhibited the typical pattern of cortisol reactivity to the online MT. Results are aligned with allostatic load models, which suggest downregulation of stress-system reactivity as a result of experiencing adversity and mental health vulnerability. Consistent with in-person research, this suggests that an early phenotype for the emergence of behavior problems may be linked to altered stress-system reactivity. Results hold potential clinical implications for intervention development and the future of online stress-system research. Trial Registration: Clinical Trial Registration: NCT04639557; (Building Regulation in Dual Generations-Telehealth Model [BRIDGE]).

Artificial insemination (AI) centres select bulls as calves according to their genetic breeding values and raise them until the first semen collection; yet, a high dropout rate of reared bulls is a problem for AI centres. Potential hormonal indicators of bull sexual maturation (cortisol, dehydroepiandrosterone (DHEA), testosterone, oestradiol, insulin-like growth factor 1 (IGF-1)) were observed and evaluated in relation to the performance parameters to perhaps identify candidate biomarkers allowing an early selection of bulls as suitable sires. Blood samples from 102 German Holstein calves at 4 ± 1, 8 ± 1 and 12 ± 2 months of age from six AI centres were analysed using validated immunoassays for cortisol, DHEA, testosterone, oestradiol and IGF-1. Semen analyses included native and thawed diluted semen. Bulls were classified at the first semen collection into groups with good versus poor performance (GP vs. LP). After 2 years, the subsequent differentiation was done in high (HPP), medium (MPP) and low performance persistency (LPP). Age at first semen collection was an important factor for sperm quality. Cortisol concentrations decreased with age, but the cortisol/DHEA ratio decreased with age only in GP bulls (p < .05). Oestradiol and testosterone concentrations both correlated with libido behaviour (p < .05). Testosterone and IGF-1 concentrations were higher at the time of first semen collection in GP bulls and increased with age (p < .05). In conclusion, testosterone and IGF-1 concentrations at first semen collection are associated with performance at first semen collection and future performance persistency, and might be useful early biomarkers for consistent sperm producing bulls on AI centres.

Although neighborhood contexts serve as upstream determinants of health, it remains unclear how these contexts \"get under the skin\" of Mexican-origin youth, who are disproportionately concentrated in highly disadvantaged yet co-ethnic neighborhoods. The current study examines the associations between household and neighborhood socioeconomic status (SES), neighborhood racial-ethnic and immigrant composition, and hair cortisol concentration (HCC)-a physiological index of chronic stress response-among Mexican-origin adolescents from low-income immigrant families in the United States. A total of 297 (54.20% female; mage = 17.61, SD = 0.93) Mexican-origin adolescents had their hair cortisol collected, and their residential addresses were geocoded and merged with the American Community Survey. Neighborhoods with higher Hispanic-origin and foreign-born residents were associated with higher neighborhood disadvantage, whereas neighborhoods with higher non-Hispanic White and domestic-born residents were associated with higher neighborhood affluence. Mexican-origin adolescents living in neighborhoods with a higher proportion of Hispanic-origin residents showed lower levels of HCC, consistent with the role of the ethnic enclave. In contrast, adolescents living in more affluent neighborhoods showed higher levels of HCC, possibly reflecting a physiological toll. No association was found between household SES and HCC. Our findings underscore the importance of taking sociocultural contexts and person-environment fit into consideration when understanding how neighborhoods influence adolescents\' stress physiology.

BACKGROUND: The U.S. Marine Corps (USMC) recruit training is a 13-week preparatory period for military service men and women. Differences in absolute performance capabilities between sexes may impact physical and physiological responses to the demands of recruit training. The purpose of this study was to monitor U.S. Marine Corps recruits throughout recruit training to comparatively assess workload, sleep, stress, and performance responses in men and women.
METHODS: A total of 281 recruits (men = 182 and women = 99; age = 19 ± 2 years) were monitored and tested. Workload, sleep, and stress assessments occurred at week 2, week 7/8, and week 11 of training. Workload (energy expenditure per kg body mass [EEREL], distance [DIS], steps) and sleep (continuity and duration) were tracked over 72-hour periods using wearable accelerometry and heart rate technology. Stress responses were determined through salivary cortisol analyses. Performance testing, consisting of countermovement vertical jump (CMJ) and isometric mid-thigh pull (IMTP) performance relative to body mass, occurred at weeks 2 and 11. Linear mixed models were used to test for sex, time, and sex-by-time interactions (α < .05).
RESULTS: On average, recruits covered 13.0 ± 2.7 km/day, expended 3,762 ± 765 calories/day, and slept 6.2 ± 1.1 hours/night. Sex-by-time interactions were found for DIS, steps, sleep duration, cortisol, and CMJREL performance (P < .05). Planned contrasts revealed that men covered more DIS than women at week 7/8 (P < .001). Women experienced greater step counts compared to men at week 11 (P = .004). Women experienced no significant change in sleep duration (P > .05), whereas men increased sleep duration from week 2 to week 7/8 (P = .03). Women experienced greater sleep duration at week 2 (P = .03) and week 11 (P = .02) compared to men. Women exhibited higher cortisol levels than men at week 2 (P < .001) and week 11 (P < .001). Women experienced declines in cortisol at week 7 compared to week 2 (P < .001). Men experienced no changes in cortisol response at any timepoint (P > .05). Both sexes experienced declines in CMJREL from week 2 to week 11 (P > .001). Sex main effects were observed for EEREL, DIS, CMJREL, and IMTPREL (P < .05) with men experiencing greater overall workloads and producing greater strength and power metrics. Sex main effects were also found for sleep continuity and cortisol (P < .05), for which men experienced lower values compared to women. Time main effects were observed for EEREL, DIS, steps, cortisol, CMJREL, and IMTPREL (P < .05).
CONCLUSIONS: This study not only highlights the known sex differences between men and women but also sheds light on the different physical and physiological responses of each sex to military training. Interestingly, the greatest physical demands incurred earlier in the training cycle. Despite declining workloads, the stress response was maintained throughout the training, which may have implications for adaptation and performance. In addition, average sleep duration fell notably below recommendations for optimizing health and recovery. Effectively monitoring the demands and performance outcomes during recruit training is essential for determining individual fitness capabilities, as well as establishing the effectiveness of a training program. Individual performance assessments and adequately periodized workloads may help to optimize recruit training for both men and women.

With advancements in medical oncology, immune checkpoint inhibitors (ICIs) have become the first-line treatment for many malignancies. ICIs play a significant role in improving cancer prognosis, but a series of immune-related adverse events (irAEs), including immune-related endocrine events (irEEs), caused by ICIs have also aroused concerns. Rapid clinical identification of irAEs caused by ICIs is particularly important. We describe a case of secondary adrenocortical insufficiency (AI) after PD-1 treatment in a postoperative patient with endometrial cancer. A 73-year-old female patient developed anorexia, nausea, vomiting, malaise, electrolyte disturbances, ineffective symptomatic treatment, and decreased serum adrenocorticotropin and cortisol levels six months after retifanlimab treatment. The vomiting resolved, and the electrolyte levels were corrected after 3 days of treatment with glucocorticoids (hydrocortisone, intravenous, 200 mg/day). When patients present with gastrointestinal symptoms, such as poor appetite and nausea, not only symptomatic treatment but also a search for the etiology behind the symptoms is needed, especially in immunotherapy patients who should undergo a thorough evaluation of the endocrine system and be alert for adrenocortical insufficiency.