Plasma Cortisol Research Articles

The impact of net cleaning on fecal cortisol metabolites in farmed Atlantic Salmon

Stress assessment is crucial in aquaculture to ensure and improve the health and well-being of production animals including fish. The primary objective of this study was to utilize the assessment of fecal cortisol metabolites (FCMs) as a low-invasive stress determination method for farmed Atlantic salmon (Salmo salar L.) and to suggest an appropriate sampling timeframe for this measurement.Blood, mid-intestinal contents, and feces samples were collected before, during, and at 2 and 20 h after a stress-inducing event, namely, net cleaning. Plasma cortisol (PC) and its metabolite levels in the mid-intestinal contents (MICMs) and FCMs were assessed by an enzyme-linked immunosorbent assay (ELISA). The research reveals a distinctive temporal profile, with a sequential elevation in levels of PC, MICMs and FCMs in response to the effects of net cleaning. Peak FCMs levels were observed approximately 20 h after net cleaning and were significantly higher than peak PC levels (P < 0.05). The findings suggest that FCMs are a promising indicator for acute stress assessment. To enhance the understanding and improve the applicability of FCMs as stress indicators in fish farming practices the critical challenges regarding feces sampling and FCMs analyses are further discussed. Future research aimed at developing practical protocols and industry standards will emphasize method validation and include a greater number of sampling points as well as an expanded experimental period.This study signifies a crucial step toward understanding the role of FCMs as a reliable stress indicator in fish. It underscores the importance of accounting for the delayed and extended sampling patterns when assessing stress in aquatic settings. Moreover, it offers a less invasive and more labor-efficient approach for monitoring the overall health and welfare of salmonids than PC analysis, thereby promoting sustainability in this vital industry.

Differential tissue immune stimulation through immersion in bacterial and viral agonists in the Antarctic Notothenia rossii

The genome evolution of Antarctic notothenioids has been modulated by their extreme environment over millennia and more recently by human-caused constraints such as overfishing and climate change. Here we investigated the characteristics of the immune system in Notothenia rossii and how it responds to 8 h immersion in viral (Poly I:C, polyinosinic: polycytidylic acid) and bacterial (LPS, lipopolysaccharide) proxies. Blood plasma antiprotease activity and haematocrit were reduced in Poly I:C-treated fish only, while plasma protein, lysozyme activity and cortisol were unchanged with both treatments. The skin and duodenum transcriptomes responded strongly to the treatments, unlike the liver and spleen which had a mild response. Furthermore, the skin transcriptome responded most to the bacterial proxy (cell adhesion, metabolism and immune response processes) and the duodenum (metabolism, response to stress, regulation of intracellular signal transduction, and immune system responses) to the viral proxy. The differential tissue response to the two proxy challenges is indicative of immune specialisation of the duodenum and the skin towards pathogens. NOD-like and C-type lectin receptors may be central in recognising LPS and Poly I:C. Other antimicrobial compounds such as iron and selenium-related genes are essential defence mechanisms to protect the host from sepsis. In conclusion, our study revealed a specific response of two immune barrier tissue, the skin and duodenum, in Notothenia rossii when exposed to pathogen proxies by immersion, and this may represent an adaptation to pathogen infective strategies.

Abstract 1015: Potential of kava in reducing lung cancer risk and associated disparities: Mechanism-based biomarker discovery and analysis

Abstract Background: Lung cancer is the leading cause of cancer-related deaths. Tobacco smoke is well-recognized as the dominant risk factor. Stress, lung inflammation, air pollution and other factors also contribute to the risk of developing lung cancer Racial/ethnic disparities in lung cancer risks exit as well. The quantitative contributions of different these risk factors to lung cancer and associated disparities, however, have not been systematically characterized. One major barrier is the lack of tools to non-invasively and objectively quantify these risk factors, which precludes the identification of high-risk individuals and the development of effective prevention. Data from our group, particularly results from a pilot clinical trial, suggest that kava, traditionally consumed in the South Pacific Islands as a beverage to reduce stress and promote relaxation, may holistically reduce lung cancer risk by impacting multiple factors that contribute to lung cancer risk. Aim: This study aims to discover mechanism-based non-invasive biomarkers reflective of different lung cancer risk factors and explore their potential roles in lung cancer risk disparities. Such biomarkers are also employed to characterize the holistic effects of kava in reducing lung cancer risk and its potential in mitigating associated disparities. Results and Analysis: One-week of kava significantly reduced the level of nicotine exposure among smokers, quantified by the Total Nicotine Equivalents (TNE) in the 24-h urine sample. Excitingly the reduction in TNE appeared to be higher among African American smokers in comparison to participants of other race/ethnicity. Biomarkers for stress (plasma cortisol and urinary total cortisol equivalents (TCE)) were significantly reduced upon one-week kava use, which may mechanistically contribute to the reductions in tobacco use. The reduction in plasma cortisol and TCE were higher among African American smokers as well. One-week kava exposure also increased urinary excretion of total NNAL and reduced urinary 3-methyladenine (3-mA) in participants, suggestive of its ability to reduce the carcinogenicity of nicotine-derived nitrosamine ketone (NNK). Kava effects on NNAL and 3mA were again more pronounced among African American smokers. Conclusion and future directions: These results demonstrate the potential of mechanism-based biomarkers in investigating lung cancer risks and associated disparities. Such biomarkers may also facilitate the translational development of effective and targeted interventions, such as kava, which may not only reduce lung cancer risk but also mitigate the associated disparities. Additional mechanism-based biomarkers on other tobacco carcinogens and inflammation are currently under development. Two clinical trials are ongoing that the current clinical samples will help validate these discoveries. Citation Format: Chengguo Xing, Breanne Freeman, Jessica Mamallapalli, Allison Lynch, Naomi Fujioka, Ramzi G. Salloum, John Malaty, Frank Orlando, Zhiguang Huo. Potential of kava in reducing lung cancer risk and associated disparities: Mechanism-based biomarker discovery and analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1015.

Stressing out-carp edema virus induces stress and modulates immune response in common carp.

Carp edema virus (CEV) is a fish poxvirus that primarily infects the gills of common carp. CEV causes koi sleepy disease (KSD), which is highly contagious and can result in mortality of up to 100%. In the present study, we analyzed the stress and immune responses during KSD in two strains of common carp with different resistance to CEV: susceptible koi and resistant Amur sazan. Experiments were performed at two temperatures: 12°C and 18°C. In the case of koi carp, we also analyzed the effect of supplementation of 0.6% NaCl into tank water, which prevents mortality of the CEV-infected fish (salt rescue model). We found that CEV-infected koi kept at 18°C had the highest viral load, which correlated with the most severe histopathological changes in the gills. CEV infection resulted in the activation of stress response reflected by the upregulated expression of genes involved in stress response in the stress axis organs and increased levels of cortisol and glucose in the blood plasma. These changes were the most pronounced in CEV-infected koi kept at 18°C. At both temperatures, the activation of antiviral immune response was observed in koi kept under freshwater and NaCl conditions upon CEV infection. Interestingly, a clear downregulation of the expression of adaptive immune genes was observed in CEV-infected koi kept under freshwater at 18°C. CEV induces a stress response and modulates adaptive immune response in koi, and this is correlated with the level of viral load and disease development.

Behavioral and physiological responses of horses to ground-based adaptive horsemanship lessons for veterans with post-traumatic stress disorder (PTSD)

Little literature exists on horses in adaptive horsemanship (AH) despite concerns about their well-being. The study objective was to evaluate behavioral and physiological responses of horses to ground-based AH lessons for veterans with post-traumatic stress disorder (PTSD). Lessons were expected to alter horses’ hormone concentrations, behavior, and muscle activity. Geldings were assigned to AH (n=6; 20.3 ± 1.9 yrs., mean ± SE) or control (CON; stall in arena, n=6; 13.8 ± 1.7 yrs.) conditions for 8-week sessions based on current occupation (AH = equine-assisted services; CON = recreational riding). Plasma cortisol, epinephrine, norepinephrine, and oxytocin concentrations from samples at 0 (start of lesson), 3, 5, 25, and 30 (end) min were determined using assays validated in horses. Surface electromyography (sEMG) (masseter and brachiocephalic; Noraxon, Scottsdale, AZ, USA) and video were recorded continuously. Average rectified values (ARV) and median frequency (MF) were calculated (100 ms) after sEMG data were normalized, rectified, and filtered. The number, number of unique, and duration of stress related behaviors (ethogram) were recorded by three trained (ĸ ≥ 0.7) observers. Data were analyzed with repeated measures ANOVAs (significance P ≤ 0.05) with fixed effects of treatment, time point, week, and their interactions as appropriate and random effect of horse. CON horses had elevated cortisol concentrations (P = 0.0023) at 25 and 30 min. AH horses displayed fewer (P ≤ 0.0491) stress related and unique behaviors. CON horses were described as more (P < 0.0001) anxious, nervous, and stressed than AH horses (calm, comfortable, patient, and relaxed) in qualitative behavior analysis (22 observers). AH horses were less stressed than CON horses.

Comparing physiological responses of acute and chronically stressed diploid and triploid Atlantic salmon (Salmo salar)

We compared the performance and physiological response of diploid and triploid Atlantic salmon (Salmo salar) following 21 days of either unpredictable chronic stress (UCS) or no disturbance (control). Thereafter, all four groups were challenged with a novel acute stressor consisting of crowding, netting and transfer into another tank. Growth was monitored during the 21-day period, and stress response to the novel acute stress challenge was assessed by blood chemistry parameters and pituitary gene expression. Plasma parameters were analyzed before (0) and 15, 30, 45, 60, 90, 120, 240, and 300 min after acute stress induction, whereas gene expression was analyzed at 0, 30, 60, 120, and 240 min. The results showed: a) similar growth rate and condition factor reductions from UCS in triploids and diploids, b) higher post-stress plasma Acth and cortisol levels in triploids compared with diploids, c) wider post-stress fluctuations in most of the other plasma parameters for triploids compared with diploids, particularly for glucose and lactate, d) pomca1, pomcb, crf-r1a and crf-r1b mRNA levels were more upregulated in control diploids than control triploids, and e) only minor changes in pituitary gene expression from UCS in both diploids and triploids, but with a noticeable upregulation of pomca2 and crf-r1a and crf-r1b in the triploids. Our results suggest that triploid Atlantic salmon have a higher energy cost in response to stress than diploids salmon. This can make them more sensitive to suboptimal conditions and episodes of acute and chronic stress.

Efficacy and Safety of Lidocam Topical Gel (4% Lidocaine-0.3% Meloxicam) for Pain and Inflammation Management during Castration and Tail Docking in Piglets.

(1) Background: It has been well established that castration and tail docking are both painful during and following the procedure, yet there are limited convenient and effective products to address both short-term and long-term pain. Lidocam Topical Gel (LTG) (4% lidocaine and 0.3% meloxicam) was developed to address industry needs for an effective and safe product to address animal welfare concerns regarding castration and tail docking in piglets. (2) Methods: Study 1: Male piglets aged 4-8 days of age were treated with LTG (n = 30) or a control gel (n = 30). Approximately 30 min after application of the gel, the piglets were surgically castrated and tail docked. The efficacy of pain control during the surgical procedures and post-procedure (24 h) pain and inflammation control were evaluated using both behavioral and physiological measurements. Study 2: Meloxicam residue depletion following LTG treatment was followed for 28 days. Study 3: Clinical and pathological safety were evaluated in five groups of eight piglets receiving LTG with: (1) no treatment, (2) nominal topical dose, (3) two times the nominal topical dose, (4) three times the nominal topical dose, and 5) one times the nominal topical dose and 2 mL of LTG by oral gavage daily for 3 days. (3) Results: LTG-treated piglets had a significant reduction in electrocutaneous stimulation response before the procedures and 4 and 24 h post-procedures. Stress vocalization intensity and duration were less in piglets receiving LTG during the surgical procedures. Plasma cortisol and substance P were significantly lower in LTG-treated piglets 3 h after castration and tail docking. The weight and average daily gain were significantly increased in piglets receiving LTG. LTG did not interfere with wound healing or cause irritation at the application sites. There were no abnormal clinical or pathological findings associated with the use of LTG at three times the nominal dose given daily for three days. As meloxicam persisted in the application site tissue, a slaughter withdrawal time of 24 days was determined. (4) Conclusions: When applied to the skin 30 min before castration and tail docking, LTG is effective in surgical pain control and provides post-surgical pain control for up to 24 h. LTG is safe for use in piglets and provides an acceptable withdrawal time for commercial use. LTG is a potentially effective product for commercial use for piglet castration and tail docking.

Air bubble curtain improves the welfare of captive rainbow trout fry and fingerlings

Fish welfare is becoming a priority for the fish farming industry. The search for practical, easy-to-implement methods to promote farmed fish welfare is therefore essential. Environmental enrichment aims to improve the psychological and physiological needs of a captive animal by increasing the complexity of its environment. During previous studies, we observed that fish seemed to be positively affected by short diffusions of air bubbles. In this study, we evaluated the effects of an innovative enrichment strategy consisting of introducing into the tank at the earliest stages of life, a pipe generating a curtain of air bubbles. Using rainbow trout (Oncorhynchus mykiss) as a captive fish model, we compared the short- (∼7 weeks) and long-term (∼21 weeks) effects of this bubble curtain diffused for one hour four times a day (Bubble condition) to a standard condition without bubbles (Control) on fish growth, aggressive and abnormal behaviors, as well as on fish motivation to access a bubble curtain, their emotional responses and their learning abilities. We found that bubble diffusion decreased aggressive and abnormal behaviors during diffusions in both the short-term and the long-term experiments. In the long-term experiment, this decrease was also observed during feedings and neutral periods when no bubble was diffused. Bubbles were found to be attractive for young Control fish (bubble-naive fish) subjected to a motivation test in the short-term experiment. When subjected to the emotional reactivity test, Bubble fish seemed less fearful, exhibiting a lower maximum velocity than Control fish in the long-term experiment only. However, the other behavioral parameters measured during this test, appetite and plasma cortisol levels were similar between treatments, irrespective of the experimental period. The latency to consume the reward observed in the spatial learning test in the long-term experiment was decreased in Bubble fish compared with Control fish, showing enhanced learning abilities in fish that experienced bubbles for 21 weeks. Growth parameters and fin erosion index did not differ between treatments. We conclude that repeated bubble diffusions act as an environmental enrichment for fish, combining physical, occupational, and sensory enrichment via the tactile stimulations provided by the air bubbles. This type of enrichment had a positive impact on the behavior of farmed rainbow trout in the long term, and would make it possible to integrate the notion of “positive welfare” into fish farms, while guaranteeing easy technical maintenance.

Genetic group and heterosis in the behavioural evolution of steers during finishing in confinement

Crossbreeding is one way of achieving complementarity between breeds in relation to economically important characteristics; in addition, it allows the effect of heterosis to be exploited. The aim of this study was to measure the behavioural evolution of different genetic groups and mating systems in continuous alternating crosses of Charolais and Nellore cattle. Seventy-nine purebred Charolais (C) and Nellore (N) steers were evaluated during finishing in confinement, together with their second (3/4C 1/4 N and 3/4 N 1/4C), third (5/8C 3/8 N and 5/8 N 3/8C) and fourth generation (11/16C 5/16 N and 11/16 N 5/16C) crosses. The confinement period was 97 days, including 13 days for adaptation to the environment and feeding regime. Behavioural assessments were carried out when weighing, evaluating the composite scale score, time taken to exit the scales, measurement of flight distance, location of the facial hair whorl, and plasma cortisol level at slaughter. The Charolais animals showed a better composite scale score, longer exit time and shorter flight distance than the Nellore animals. For generation 3 (5/8 animals), the inclusion of Charolais genes afforded a higher composite scale score in each of the assessments, longer flight time in the assessments at 14 and 77 days, shorter flight distance in each of the assessments, with the facial hair whorl positioned further below the eye line, determining animals of a calmer behaviour. Purebred Nellore and predominantly Nellore animals from the third generation of crosses were higher in cortisol at slaughter than the purebred Charolais or predominantly Charolais animals, showing significant heterosis only in the second generation. Bos taurus animals are calmer and have a more suitable temperament than Bos indicus, however, the behaviour of zebu cattle can improve as the period of confinement increases, with the type of handling affecting behaviour and reactivity throughout the assessments.

88 Impacts of trace mineral source and ancillary drench on steer performance during a 60-day backgrounding phase

Abstract This experiment evaluated the impacts of supplementing organic complexed Cu, Co, Mn, and Zn on productive and health responses of high-risk beef cattle during a 60-d backgrounding phase. Crossbred steers (n = 120) were purchased at auction and transported to the experimental facility. Steer BW was recorded at arrival (d -1; initial shrunk BW = 227.7 ± 1.3 kg). On d 0, steers were ranked by BW and allocated to 1 of 8 groups (8 steers/group) and housed in drylot pens (6 m x 12 m) equipped with GrowSafe automated feeding systems (Model 8000; 2 bunks/pen; d 0 to 60). Groups were randomly assigned to receive a total mixed ration (TMR; 47% corn) containing: 1) sulfate sources of Cu, Co, Mn, and Zn (INR; n = 40); 2) organic complexed sources of Cu, Mn, Co, and Zn (AAC; Zinpro Availa 4; Zinpro Corp., Eden Prairie, MN; n = 40); or 3) AAC and an organic complexed trace mineral drench (APF; 30 mL/hd; Zinpro ProFusion, Zinpro Corp.) on d 0 and ancillary to morbidity treatment (n = 40). Diets provided the same daily amount of energy, protein, macro minerals and trace minerals based on 7 g/steer daily of Zinpro Availa 4. Steers were assessed for bovine respiratory disease (BRD) signs daily. Liver biopsies were performed on day 0, 28 and 60. Final BW was recorded on d 60 and 61. Blood samples were collected on d 0, 2, 6, 10, 13, 21, 28 and 45. No treatment differences were detected (P ≥ 0.23) for TMR intake, final BW, ADG, feed efficiency, or BRD incidence. Mean liver Co concentrations were greater (P = 0.02) in AAC and APF compared with INR steers. Mean liver Cu was greater (P = 0.02) in APF compared with AAC steers. Liver Zn tended to be greater (P = 0.10) on d 28 but less (P = 0.05) on d 60 for INR compared with AAC and APF steers. Plasma cortisol was least (P = 0.05) for steers supplemented with AAC on d 6, whereas AAC steers tended to have greater (P = 0.09) plasma cortisol on d 13 compared with APF. Plasma haptoglobin tended to be greater (P ≤ 0.10) for INR steers on d 28 and 45 compared with AAC and APF. While supplementing cattle with AAC or INR results in similar animal performance and clinical disease, AAC and APF reduces stress and acute phase protein responses.

Methanol leaf extract of Leptadenia hastata ameliorates chronic, unpredictable, mild stress-induced depression

Leptadenia hastata (Pers) Decne is a tropical herb widely used in the phytotherapy of neuropsychiatric disorders, including depression. Despite the availability of synthetic antidepressant drugs, depression remains a major medical problem. The study aimed to evaluate the effect of methanol leaf extract of Leptadenia hastata (LHME) on chronic unpredictable mild stress-induced depression. Acute toxicity of Leptadenia hastata was determined using Organization for Economic Co-operation and Development (OECD) guidelines. The chronic unpredictable mild stress (CUMS) model-induced depression involves the evaluation of baseline behavioural changes in the sucrose preference test, open field test, and tail suspension test. The brain-derived neurotrophic factor (BDNF) concentrations and serum cortisol were assessed using an enzyme-linked immunosorbent assay (ELISA). The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were also assessed using standard procedure. The median lethal dose (LD50) value was &gt; 5000 mg/kg. LHME at doses of 250 – 1000 mg significantly (p&lt;0.01) decreased CUMS-induced depression in a dose-dependent manner. LHME significantly (p&lt;0.01) reversed depression associated weight loss from 14.00±0.62 g in week two to 22.57±1.13 g in week five of the experiment. It also increased sucrose consumption in the sucrose preference test (SPT) from 4.29±0.52 ml in week two to 9.71±0.68 ml in week five. The LHME also significantly (p&lt;0.01) decreased the duration of immobility from 190.00±4.55 sec in week two to 158.00±3.83 sec in week five in the tail suspension test (TST). Furthermore, LHME at the tested dose significantly (p&lt;0.01) increased the locomotor activity from 36.29±1.25 sec in week two to 62.43±1.73 sec in week five in the open field test (OFT). LHME significantly (p&lt;0.01) and dose-dependently increased the levels of BDNF (204.74±22.97 pg/ml) and decreased the levels of plasma cortisol (0.98±0.06 ng/ml). However, treatment with LHME and the standard drug imipramine did not significantly change SOD activity and the MDA level in CUMS-induced mice. The findings demonstrated that LHME ameliorates CUMS-induced depressive-like behaviours, and its effect is possibly mediated via the neuroendocrine (cortisol) and neurotrophic (BDNF).

Phytogenics enhance welfare and vaccine efficacy against Vibrio anguillarum in European seabass (Dicentrarchus labrax) juveniles

Disease prevention is pivotal in aquaculture, and while vaccines offer protective immunity, challenges such as cost and low efficacy persist. The present study investigated the potential of plant-derived compounds, known as phytogenics, to bolster the effectiveness of vaccines against vibriosis in European seabass. Two phytogenic blends, namely PHYTO1 (terpenes) and PHYTO2 (terpenes and flavonoids) were supplemented to a commercial diet to obtain three experimental diets: a non-supplemented control diet, PHYTO1 (a 200-ppm blend of garlic and Lamiaceae oils with 87.5 mg kg−1 terpenes), and PHYTO2 (a 1000 ppm blend containing citrus fruits, Asteraceae and Lamiaceae oils with 57 mg kg−1 terpenes and 55 mg kg−1 flavonoids). Following vaccination by bath immersion, juvenile European seabass were divided into groups and fed one of the three diets for 30 days. After this feeding period, fish were anesthetized and boosted with a single dose of vaccine through intraperitoneal injection. They continued to be fed their respective diets for another 30 days. At day 60, after the priming vaccination, fish were challenged with Vibrio anguillarum via intraperitoneal injection. Various parameters were measured at different time points post each vaccination, including total weight, circulating plasma cortisol and glucose levels, serum immunoglobulin M (IgM) titers, antioxidant power of leucocytes, and the expression of several antioxidant and immune-related genes. The results showed that fish fed with phytogenic supplements did not differ in weight compared to the control group. However, they exhibited lower plasma cortisol and glucose levels, increased IgM titers, and enhanced antioxidant protection and antioxidant power of head kidney leucocytes. In addition, phytogenics upregulated several immune-related genes in the gills and head kidney immediately after each vaccination. Notably, PHYTO2, enriched with flavonoids and terpenes, exhibited an even more pronounced positive effect on boosted fish by reducing vaccine-associated stress while improving antioxidant protection and modulating the vaccine-induced immune response. This synergistic effect of vaccination combined with phytogenics introduces new pathways for enhancing fish health in aquaculture.

Thymic Atrophy and Immune Dysregulation in Infants with Complex Congenital Heart Disease

Congenital heart disease (CHD) is the most common birth defect, and up to 50% of infants with CHD require cardiovascular surgery early in life. Current clinical practice often involves thymus resection during cardiac surgery, detrimentally affecting T-cell immunity. However, epidemiological data indicate that CHD patients face an elevated risk for infections and immune-mediated diseases, independent of thymectomy. Hence, we examined whether the cardiac defect impacts thymus function in individuals with CHD. We investigated thymocyte development in 58 infants categorized by CHD complexity. To assess the relationship between CHD complexity and thymic function, we analyzed T-cell development, thymic output, and biomarkers linked to cardiac defects, stress, or inflammation. Patients with highly complex CHD exhibit thymic atrophy, resulting in low frequencies of recent thymic emigrants in peripheral blood, even prior to thymectomy. Elevated plasma cortisol levels were detected in all CHD patients, while high NT-proBNP and IL-6 levels were associated with thymic atrophy. Our findings reveal an association between complex CHD and thymic atrophy, resulting in reduced thymic output. Consequently, thymus preservation during cardiovascular surgery could significantly enhance immune function and the long-term health of CHD patients.

Assessing the Role of Cortisol in Anxiety, Major Depression, and Neuroticism: A Mendelian Randomization Study Using SERPINA6/SERPINA1 Variants

BackgroundPrevious evidence informed by the toxic stress model suggests that higher cortisol causes anxiety and major depression, but clinical success is lacking. To clarify the role of cortisol, we used Mendelian randomization to estimate its associations with anxiety, major depression, and neuroticism, leveraging the largest available genome-wide association studies including from the Psychiatric Genomics Consortium, the UK Biobank, and FinnGen. MethodsAfter meta-analyzing 2 genome-wide association studies on morning plasma cortisol (n = 32,981), we selected single nucleotide polymorphisms (SNPs) at p < 5 × 10−8 and r2 < 0.3 in the SERPINA6/SERPINA1 gene region encoding proteins that influence cortisol bioavailability. We applied these SNPs to summary genetic associations with the outcomes considered (n = 17,310–449,484), and systolic blood pressure as a positive outcome, using inverse-variance weighted meta-analysis accounting for correlation. Sensitivity analyses addressing SNP correlation and confounding by childhood maltreatment and follow-up analyses using only SNPs that colocalized with SERPINA6 expression were conducted. ResultsCortisol was associated with anxiety (pooled odds ratio [OR] 1.16 per cortisol z score; 95% CI, 1.04 to 1.31), but not major depression (pooled OR 1.02, 95% CI, 0.95 to 1.10) or neuroticism (β −0.025; 95% CI, −0.071 to 0.022). Sensitivity analyses yielded similar estimates. Cortisol was positively associated with systolic blood pressure, as expected. Using rs9989237 and rs2736898, selected using colocalization, cortisol was associated with anxiety in the UK Biobank (OR 1.32; 95% CI, 1.01 to 1.74) but not with major depression in FinnGen (OR 1.14; 95% CI, 0.95 to 1.37). ConclusionsCortisol was associated with anxiety and may be a potential target for prevention. Other targets may be more relevant to major depression and neuroticism.

Efficacy of nutritional selenium nanoparticles on growth performance, immune response, antioxidant capacity, expression of growth and immune-related genes, and post-stress recovery in juvenile Sobaity seabream (Sparidentex hasta)

This study evaluated the impacts of nano-Se on the growth, immunity, antioxidant capacity, physiological parameters, gene expression, and stress resistance of fingerling Sobaity seabream (Sparidentex hasta). The fish with an average weight of 21.5 ± 0.1 g were divided into four treatment groups in triplicates that received one of the test diets supplemented with varying levels of nano-Se: 0 (control), 0.5 (Se-0.5), 1 (Se-1), and 2 (Se-2) mg/Kg for 60 days. The results showed that final weight, weight gain rate, specific growth rate, feed intake, and feed conversion ratio improved with significant linear and quadratic trends (P < 0.05) in response to nano-Se-supplemented diets, and the best values were measured in the Se-2 group. Superoxide dismutase activity level remained unaffected among the four groups (P > 0.05). Catalase activity increased in nano-Se-supplemented groups, with the highest level measured in fish fed the Se-0.5 diet. Glutathione peroxidase activity levels were not significantly different between the control and nano-Se groups, but the lowest malondialdehyde concentration was detected in the Se-2 group. Nano-Se had no marked effect on total plasma Ig levels; however, the highest lysozyme activity and alternative complement activity (ACH50) were observed in the Se-0.5 and Se-2 groups, respectively. No significant differences (P > 0.05) were observed in plasma total protein, albumin, globulin, triglyceride, and thyroid hormone (T3 and T4) contents among the groups. However, the lowest cholesterol and low-density lipoprotein values and the highest high-density lipoprotein concentration were measured in the Se-2 group. The Se-0.5 and Se-1 groups exhibited significantly lower levels of aspartate aminotransferase activity, and the lowest alkaline phosphatase activity level was detected in the Se-1 group. The expression level of insulin-like growth factor I gene in all nano-Se-fed groups was significantly higher than the control. Also, the expression of interleukin-1β and lysozyme genes was significantly upregulated in nano-Se-supplemented groups, with the highest values in the Se-2 group. Following acute crowding stress, plasma cortisol and lactate levels at all post-stress time intervals were not significantly different among the experimental groups. Fish fed the Se-0.5 and Se-2 diets tended to have lower plasma glucose concentrations than other groups. In conclusion, dietary nano-Se at 2 mg/kg is recommended to promote growth performance and enhance antioxidant and immune parameters in Sobaity juveniles.

Behavioral and neurophysiological effects of buspirone in healthy and depression-like state juvenile salmon.

A proportion of farmed salmon in seawater show a behaviorally inhibited, growth stunted profile known as a depression-like state (DLS). These DLS fish are characterized by chronically elevated serotonergic signaling and blood plasma cortisol levels and the inability to react further to acute stress, which is suggestive of chronic stress. In this study, we characterize the neuroendocrine profile of growth stunted freshwater parr and confirm that they show a DLS-like neuroendocrine profile with a blunted cortisol response and no serotonergic increase in response to acute stress. Furthermore, we attempted to reverse this DLS-like profile through pharmacological manipulation of the serotonin (5-HT) system with buspirone, an anxiolytic medication that acts as a serotonin receptor agonist (i.e., decreases serotonergic signaling). We found that while buspirone decreases anxiolytic-type behavior in healthy fish, no quantifiable behavioral change was found in DLS-like fish. However, there was a physiological effect of diminished basal serotonergic signaling. This suggests that at the physiological level, buspirone appears to reverse the neuroendocrine DLS profile. With a deeper understanding of what causes DLS profiles and growth stunting in juvenile fish, steps can be taken in terms of husbandry to prevent repeated stressors and the formation of the DLS profile, potentially reducing losses in aquaculture due to chronic stress.

The Welfare of Horses Competing in Three-Barrel Race Events Is Shown to Be Not Inhibited by Short Intervals between Starts.

Equestrian sports require precise animal welfare and health evaluations. To test the hypothesis that horses maintain their welfare when subjected to two three-barrel (3TB) races with 2 min intervals, an experiment was designed to evaluate their surface temperature using infrared thermography (IRT) in regions of interest (barrel, flank, neck, jaw, corner of the mouth, and ocular caruncle) and also measure blood biomarkers (hemogram, total plasma protein, fibrinogen, urea, creatinine, GGT, CK, cortisol, IL-6, and IL-1β). Ten Quarter Horses were monitored through thermography (pre-race, +1, +4, and +24 h post-race) and blood sampling (pre-race, +1, +4, and +24 h post-race). ANOVA and Tukey test at 5% were used. IRT in six regions of interest (Left/Right-barrel, flank, neck muscles) increased at +, with no differences between values recorded at +1 and +4 when compared to those measured pre-race (p > 0.05). Plasma protein, RBC count, hemoglobin, hematocrit, WBC count, neutrophils, and lymphocytes (p < 0.05) increased immediately after the races, with recovery at +1 h. Other biomarkers did not change, including cortisol, IL-6, and IL-1β (p > 0.05). Results indicate that well-conditioned 3TB horses subjected to two races at short intervals do not show changes that could be related to impaired health or welfare.

Links between the genetic determinants of morning plasma cortisol and body shape: a two-sample Mendelian randomisation study

High cortisol production in Cushing’s syndrome leads to fat centralisation. The influence of modest cortisol variations on body shape, however, is less clear. We examined potentially causal associations between morning plasma cortisol and body shape and obesity with inverse-variance weighted random-effects models in a two-sample Mendelian randomisation analysis. We used publicly available summary statistics from the CORtisol NETwork (CORNET) consortium, UK Biobank, and the Genetic Investigation of Anthropometric Traits (GIANT) consortium. Only in women, morning plasma cortisol (proxied by ten genetic polymorphisms) was associated positively with waist size reflected in waist-to-hip index (WHI, 0.035 standard deviation (SD) units change per one SD cortisol increase; 95% confidence interval (0.002–0.067); p = 0.036) and “a body shape index” (ABSI; 0.039 (0.006–0.071); p = 0.021). There was no evidence for associations with hip index (HI) or body mass index (BMI). Among individual polymorphisms, rs7450600 stood out (chromosome 6; Long Intergenic Non-Protein-Coding RNA 473 gene, LINC00473). Morning plasma cortisol proxied by rs7450600 was associated positively with WHI and inversely with HI and BMI in women and men. Our findings support a causal association of higher morning plasma cortisol with larger waist size in women and highlight LINC00473 as a genetic link between morning plasma cortisol and body shape.

High replacement of soybean meal by different types of rapeseed meal is detrimental to rainbow trout (Oncorhynchus mykiss) growth, antioxidant capacity, non-specific immunity and Aeromonas hydrophila tolerance.

A 12-week feeding trial was conducted to evaluate the effects of replacing soybean meal with different types of rapeseed meal (RSM; Chinese 95-type (oil press model) rapeseed meal [C95RM], Chinese 200-type rapeseed meal [C200RM], cold pressed rapeseed cake [CPRC], Indian rapeseed meal [IRM] and Canadian rapeseed meal [CRM]) on growth, antioxidant capacity, non-specific immunity and Aeromonas hydrophila infection tolerance in 990 fingering (average weight 12.77 ± 0.01 g) rainbow trout (Oncorhynchus mykiss). A basal diet was prepared using fishmeal and soybean meal as the main protein sources, the other 10 diets were formulated with five types of RSM at 20% (C95RM20, C200RM20, CPRC20, IRM20, CRM20) or 35% (C95RM35, C200RM35, CPRC35, IRM35, CRM35) inclusion levels to replace iso-nitrogenous soybean meal. Regardless of the RSM source, dietary inclusion of 20% RSM significantly reduced the weight gain rate (WGR) and digestive enzymes activities (except C200RM20) of fish, but increased the blood urea nitrogen (BUN) and hepatic malondialdehyde (MDA) content (except CRM20). Fish fed with CPRC20 and IRM20 exhibited relatively higher plasma cortisol and MDA content, but lower content/activities of triiodothyronine (T3), thyroxine (T4) and glutathione peroxidase (GPx) in plasma, lysozyme (LZM) and complement 3 (C3) in serum, catalase (CAT) in liver, and respiratory burst activity (RBA) of head kidney macrophages. The intestinal and hepatic tissues fed with 20% RSM were damaged to some extent, with the CPRC20 and IRM20 groups being the most severely affected. Regardless of the RSM source, dietary inclusion of 35% RSM significantly decreased WGR and digestive enzymes activities, but significantly increased plasma BUN and MDA content. The fish fed with CPRC35 and IRM35 exhibited relatively higher plasma cortisol, MDA, serum triglyceride, BUN content, but lower content/activities of T3, T4, C3, and LZM in serum, CAT, peroxidase and GPx in plasma, CAT in liver, RBA and phagocytic activity of head kidney macrophage. The hepatic and intestinal tissues damage was the worst in the IRM35 group among the 35% RSM inclusion groups. These results indicate that including ≥20% RSM in the diet, regardless of the source, reduced the growth, antioxidant capacity, immunity, and survival to Aeromonas hydrophila infection in rainbow trout.

Pubertal glyphosate-based herbicide exposure aggravates high-fat diet-induced obesity in female mice.

Glyphosate-based herbicides (GBH) are the most widely used pesticides globally. Studies have indicated that they may increase the risk of various organic dysfunctions. Herein, we verified whether exposure to GBH during puberty increases the susceptibility of male and female mice to obesity when they are fed a high-fat diet (HFD) in adulthood. From the 4th-7th weeks of age, male and female C57Bl/6 mice received water (CTL group) or 50mg GBH /kg body weight (BW; GBH group). From the 8th-21st weeks of age, the mice were fed a standard diet or a HFD. It was found that pubertal GBH exposure exacerbated BW gains and hyperphagia induced by HFD, but only in female GBH-HFD mice. These female mice also exhibited high accumulation of perigonadal and subcutaneous fat, as well as reduced lean body mass. Both male and female GBH-HFD displayed hypertrophic white adipocytes. However, only in females, pubertal GBH exposure aggravated HFD-induced fat accumulation in brown adipocytes. Furthermore, GBH increased plasma cortisol levels by 80% in GBH-HFD males, and 180% in GBH-HFD females. In conclusion, pubertal GBH exposure aggravated HFD-induced obesity, particularly in adult female mice. This study provides novel evidence that GBH misprograms lipid metabolism, accelerating the development of obesity when individuals are challenged by a second metabolic stressor, such as an obesogenic diet.