Biological Stress Markers Research Articles

What I was thinking/what I would do differently: Biological markers and mechanisms of mental health.

At the 39th meeting of the International Society of Traumatic Stress Studies, four leading scientists and clinicians were invited to reflect on their careers, focusing on the biological mechanisms and markers of traumatic stress. Dr. Raul Andero has contributed to understanding how stress alters memory networks in the brain, influencing the development of novel treatments. Dr. Tanja Jovanovic has pioneered the measurement and mechanistic understanding of fear learning, bridging basic and clinical research. Dr. Murray B. Stein has scaled up clinical and lab observations to large populations, refining the field's understanding of traumatic stress. Dr. Arieh Y Shalev has shaped the definition of traumatic stress, pioneering the longitudinal investigation of stress and integrating advanced computational methods to identify individuals at risk. These panelists were asked to reflect on their initial problems, ambitions, concerns, and unexpected challenges, as well as the influence of their work, on new research trajectories. Their insights provide valuable lessons about the process and content of their work, and their pioneering efforts have significantly advanced our understanding of the biological mechanisms and markers of traumatic stress.

The effect of assessor visibility on student stress and anxiety in emergency care simulation assessments

BackgroundSimulation assessment can result in anxiety for students. These assessments involve being observed by assessors, so there is a significant socio-evaluative stress component which may cause greater anxiety if assessors are visible to students during assessments. The aim of this study was to determine the effect of assessor visibility on biological and physiological markers of stress and levels of anxiety experienced by pre-hospital emergency care students in a simulation assessment environment.MethodsA paired comparison, pre-post test research design was used with two conditions; an assessor visible condition with simulation assessors visible to students in the room and an assessor not visible condition with assessors not in the room but connected via video link. With a sample of 29 emergency care students anxiety was measured with the State-Trait Anxiety Inventory and stress was measured with salivary cortisol and heart rate variability (HRV).ResultsDifferences in state anxiety scores, HRV variables and salivary cortisol suggested lower stress and anxiety in the assessor visible group. Only heart rate was significantly different between the groups (p = 0.016), with a higher heart rate in the assessor not visible group.ConclusionsGreater stress and anxiety may be experienced by students during emergency care simulation assessments when assessors are not visible to students.

Assessing biological stress markers in the hair of individuals at ultra-high risk for psychosis using a novel method of extraction

Assessing biological stress markers in the hair of individuals at ultra-high risk for psychosis using a novel method of extraction

Influence of footshock number and intensity on the behavioral and endocrine response to fear conditioning and cognitive fear generalization in male rats

Foot-shock paradigms have provided valuable insights into the neurobiology of stress and fear conditioning. An extensive body of literature indicates that shock exposure can elicit both conditioned and unconditioned effects, although delineating between the two is a challenging task. This distinction holds crucial implications not only for the theoretical interpretation of fear conditioning, but also for properly evaluating putative preclinical models of post-traumatic stress disorder (PTSD) involving shock exposure. The characteristics of shocks (intensity and number) affect the strength of learning, but how these characteristics interact to influence conditioned and unconditioned consequences of shocks are poorly known. In this study, we aimed to investigate in adult male rats the impact of varying shock number and intensity on the endocrine and behavioral response to contextual fear conditioning and fear generalization to a novel environment markedly distinct from the shock context (i.e., fear generalization). Classical biological markers of stress (i.e., ACTH, corticosterone, and prolactin) were sensitive to manipulations of shock parameters, whereas these parameters had a limited effect on contextual fear conditioning (evaluated by freezing and distance traveled). In contrast, behavior in different novel contexts (fear generalization) was specifically sensitive to shock intensity. Notably, altered behavior in novel contexts markedly improved, but not completely normalized after fear extinction, hypoactivity apparently being the result of both conditioned and unconditioned effects of foot-shock exposure. The present results will contribute to a better understanding of shock exposure as a putative animal model of PTSD.

Elevated stress-responsive biomarkers are associated with HIV acquisition in young women in rural South Africa: A HPTN 068 case cohort study.

Biological markers of stress have been associated with HIV progression and pathogenesis but not with HIV incidence. We sought to determine if elevated stress-responsive biomarkers would be associated with incident HIV among adolescent girls and young women (AGYW). We conducted a case-cohort study within the HIV Prevention Trials Network (HPTN) 068 study among 949 AGYW in South Africa. Cases were AGYW who tested HIV-positive during the eight-year follow-up. Unmatched controls were randomly selected from the HIV-negative population at enrollment. Dried blood spots from cases and controls were tested from enrollment (2011-2012) for C-reactive protein (CRP), herpes simplex virus type-1 (HSV-1) antibody titers, and cytomegalovirus (CMV) antibody titers. Cox proportional hazards models estimated the association between each biomarker and time to incident HIV. Compared to AGYW with the lowest CRP levels, those with medium and high CRP levels had a higher hazard ratio (HR) of incident HIV (HR: 1.45, 95% CI: 0.95, 2.21; HR: 1.50, 95% CI: 0.98,2.30, respectively), although not statistically significant. The relative hazard of incident HIV was also higher among AGYW who were CMV seropositive vs. seronegative (low antibodies HR: 2.18, 95% CI: 1.2,3.87; medium HR: 2.25, 95% CI: 1.28,3.95; high HR: 1.78, 95% CI: 0.99,3.21). Those with the highest HSV-1 antibody levels experienced an increased hazard of HIV compared to those who were HSV-1 seronegative (HR: 1.58, 95% CI: 1.03,2.44). Biological stress may increase AGYW's susceptibility to HIV acquisition through changes in immune function, viral infection, and increased biological vulnerability to disease.

The effect of music on stress recovery

ObjectivePrevious research has suggested beneficial effects of music in reducing stress levels. However, there is no consistent conclusion demonstrating that music can contribute to stress recovery, primarily due to limitations in stress measurement, and inconsistent methodology within existing studies. Our study explores whether relaxing music, especially when self-selected, outperforms non-music acoustic, and silence conditions, fostering both subjective and biological stress recovery. MethodsOne hundred and five healthy female participants underwent the Trier Social Stress Test (TSST) before being randomly allocated to one of four conditions: condition 1 (n = 25) listened to researcher-selected relaxing music; condition 2 (n = 27) listened to self-selected relaxing music; condition 3 (n = 26) listened to the sound of rippling water; and condition 4 (n = 27) remained in silence. Stress parameters were repeatedly measured nine times before and after the TSST. Saliva samples were collected for cortisol and saliva alpha-amylase (sAA) analysis, Movisens equipment was used to measure heart rate (HR) and skin conductance levels (SCL), and Visual Analogue Scales (VAS) were used for subjective stress measurement. ResultsThe examination of SCL, and VAS scores revealed no significant changes following the four relaxation interventions. Although sAA displayed a significant main effect of condition, post hoc tests did not pinpoint specific differences. HR recovery patterns varied among the four relaxation interventions, with the sound of rippling water condition exhibiting a later significant decrease compared to the other conditions. Exploratory analyses revealed that cortisol levels continued increase in all conditions during intervention phase except the researcher-selected music condition. ConclusionsThe subjective and biological stress markers did not exhibit better recovery after the music stimulus, except for a tendency in the researcher-selected music condition to mitigate the continued increase in cortisol levels after the stress test. Our study provides the first evidence comparing the impact of researcher- and participant-selected music with silence and a non-music acoustic stimulus, on both subjective and biological stress recovery. Our findings contribute to a more nuanced understanding of the impact of music on stress recovery.

Assessing the Correlation between Allostatic Load and False-Positive Image-Guided Breast Biopsies.

Background: Allostatic load (AL) is the accumulation of physiological dysregulation attributed to repeated activation of the stress response over a lifetime. We assessed the utility of AL as a prognostic measure for high-risk benign breast biopsy pathology results. Method: Eligible patients were women 18 years or older, with a false-positive outpatient breast biopsy between January and December 2022 at a tertiary academic health center. AL was calculated using 12 variables representing four physiological systems: cardiovascular (pulse rate, systolic and diastolic blood pressures, total cholesterol, high-density lipoprotein, and low-density lipoprotein); metabolic (body mass index, albumin, and hemoglobin A1C); renal (creatinine and estimated glomerular filtration rate); and immune (white blood cell count). Multivariable logistic regression was used to assess the association between AL before biopsy and breast biopsy outcomes controlling for patients' sociodemographics. Results: In total, 170 women were included (mean age, 54.1 ± 12.9 years): 89.4% had benign and 10.6% had high-risk pathologies (radial scar/complex sclerosing lesion, atypical ductal or lobular hyperplasia, flat epithelial atypia, intraductal papilloma, or lobular carcinoma in-situ). A total of 56.5% were White, 24.7% Asian, and 17.1% other races. A total of 32.5% identified as Hispanic. The mean breast cancer risk score using the Tyrer-Cuzick model was 11.9 ± 7.0. In multivariable analysis, with every one unit increase in AL, the probability of high-risk pathology increased by 37% (odds ratio, 1.37; 95% confidence interval, 1.03, 1.81; p = 0.03). No significant association was seen between high-risk pathology and age, ethnicity, breast cancer risk, or area deprivation index. Conclusion: Our findings support that increased AL, a biological marker of stress, is associated with high-risk pathology among patients with false-positive breast biopsy results.

Trends in hair cortisol from preconception to the postpartum period

IntroductionCortisol is a biological marker of stress, and its levels reflect the hypothalamic-pituitary-adrenal (HPA) axis response to stress over time. Saliva, blood, and urine cortisol reflect acute stress, whereas assessment of hair cortisol is a better reflection of chronic stress. There is limited information on hair cortisol concentration (HCC) in the perinatal period, particularly, in the preconception and postpartum periods. In addition to being a biomarker for stress, high levels of cortisol are typically associated with poor psychosocial outcomes, and adverse pregnancy outcomes. The objectives of this study were: (1) to measure HCC from six months preconception to six months postpartum; (2) to examine the relationship between HCC and demographic characteristics, depressive symptoms, and perceived stress in the first six months postpartum period; (3) and to assess the associations between HCC and systemic inflammatory markers in the first six months postpartum. MethodsThe analysis included 96 women from a longitudinal study with up to 3 study visits in the first six months postpartum. Blood and hair samples were collected at 1–2 months (PP1), 3–4 months (PP2), and 5–6 months (PP3) postpartum. We obtained sociodemographic information, depressive symptoms, and perceived stress scores at PP1-PP3. To quantify cortisol levels over time, 8 segments were derived corresponding to 6 (PC1) and 3 (PC2) months preconception as well as for each trimester (T1-T3) and postpartum (PP1-PP3). Eight cytokines (Granulocyte-macrophage colony-stimulating factor (GM-CSF), Interferon- gamma [IFN- γ], Interleukin [IL]-10, IL-2, IL-4, IL-6, IL-8, and Tumor necrosis factor-alpha (TNF- α) were measured in plasma in the postpartum samples. Univariate, bivariate, correlations, and linear mixed modelling were performed using SAS 9.4. Multiple testing correction was conducted for correlations using false discovery rate and a Q value of <0.05 was deemed significant. ResultsMedian HCC varied over time peaking in the third trimester and declining in the postpartum. Significant differences were noted in median cortisol levels by race with Black/African American postpartum women experiencing higher levels at all timepoints. Significantly, higher median cortisol levels were also observed at PP1 and PP2 for mothers who reported their relationship status as single. Ethnicity, education, median age, depressive symptoms, and perceived stress were not associated with median cortisol levels. Pro-inflammatory cytokines IFN- γ (q= 0.01; r=-0.50) and IL-8 (q= 0.00; r=-0.55) showed correlations with HCC at PP1. ConclusionHCC increased during pregnancy, peaking at T3 and declining PP consistent with previous work. Black/African American women and single women have significantly higher median cortisol levels in the postpartum period. The marked increase of HCC in Black women may be an important factor in understanding maternal health racial inequities. Future studies should investigate how the relationships between HCC, sociodemographics, and systemic cytokines impact perinatal outcomes.

Protective effects of levosimendan in scopolamineinduced mice model of Alzheimer's disease

Objectives. Alzheimer's disease is the most prevalent neurodegenerative disease and accounts for approximately 70% of all dementia cases worldwide. Levosimendan is a positive inotropic agent with well-documented pleiotropic properties, including anti-inflammatory and antioxidant effects. The current research evaluated the possible effect of levosimendan alone or in combination with donepezil against scopolamine-induced mice models of Alzheimer’s disease. Material and methods. Mice were divided into five groups: the control group, the induction group (scopolamine 1 mg/kg/i.p once daily for 7 days), other groups that received the tested drugs prophylactically for 2 weeks and then induced with scopolamine together with the same doses of the tested drug for one week. These treatment groups included the levosimendan group (200 μg/kg i.p. once weekly for 3 weeks), the donepezil group (5 mg/kg i.p once daily for 3 weeks), and the fifth group received a combination of levosimendan (200 μg/ kg i.p. once weekly) and donepezil (5mg/kg i.p once daily). Cognitive performance was assessed by conducting behavioral tests (a novel objective recognition test and Y Maze test), and the levels of biological markers of oxidative stress (SOD and MDA), inflammatory cytokines (TNFα, IL1β and IL-6) and AChE in the brain tissue homogenate were measured utilizing available ELISA kits. Results. Levosimendan preserved the spatial memory and recognition function and significantly reduced: ACHE level, IL-6, IL-1β, TNF-α, and MDA levels, and significantly increased SOD level in mice brain tissue homogenate as compared to the induction group. And the combination of levosimendan with donepezil resulted in non-significant improvement as compared to each drug alone specifically in ACHE level reduction and oxidative stress markers. Conclusions. The current study showed that levosimendan produced a neuroprotective effect against the scopolamine-induced mice models of AD. This effect may be in part attributed to the antioxidant and anti-inflammatory properties of levosimendan.

A phase 1 proof-of-concept study evaluating safety, tolerability, and biological marker responses with combination therapy of CTLA4-Ig and interleukin-2 in amyotrophic lateral sclerosis.

To determine whether a combination therapy with abatacept (CTLA4-Ig) and interleukin-2 (IL-2) is safe and suppresses markers of oxidative stress, inflammation, and degeneration in ALS. In this open-label study, four participants with ALS received subcutaneous injections of low dose IL-2 (1 × 106 IU/injection/day) for 5 consecutive days every 2 weeks and one subcutaneous injection of CTLA4-Ig (125 mg/mL/injection) every 2 weeks coinciding with the first IL-2 injection of each treatment cycle. Participants received a total of 24 treatment cycles during the first 48 weeks in this 56-week study. They were closely monitored for treatment-emergent adverse events (TEAEs) and disease progression with the ALSFRS-R. Phenotypic changes within T cell populations and serum biological markers of oxidative stress [4-hydroxynonenal (4-HNE) and oxidized-LDL (ox-LDL)], inflammation (IL-18), and structural neuronal degeneration [neurofilament light chain (Nf-L)] were assessed longitudinally. CTLA4-Ig/IL-2 therapy was safe and well-tolerated in all four participants over the 56-week study. During the first 24 weeks, the average rate of change in the ALSFRS-R was +0.04 points/month. Over the 48-week treatment period, the average rate of change was -0.13 points/month with one participant improving by 0.9 points/month while the other three participants experienced an average decrease of -0.47 points/month, which is slower than the average - 1.1 points/month prior to initiation of therapy. Treg suppressive function and numbers increased during treatment. Responses in the biological markers during the first 16 weeks coincided with minimal clinical progression. Mean levels of 4-HNE decreased by 30%, ox-LDL decreased by 19%, IL-18 decreased by 23%, and Nf-L remained the same, on average, in all four participants. Oxidized-LDL levels decreased in all four participants, 4-HNE and IL-18 levels decreased in three out of four participants, and Nf-L decreased in two out of four participants. The combination therapy of CTLA4-Ig and IL-2 in ALS is safe and well-tolerated with promising results of clinical efficacy and suppression of biomarkers of oxidative stress, neuroinflammation and neuronal degeneration. In this open-label study, the efficacy as measured by the ALSFRS-R and corresponding biomarkers suggests the therapeutic potential of this treatment and warrants further study in a phase 2 double-blind, placebo-controlled trial. ClinicalTrials.gov, NCT06307301.

Stress reduction through taiji: a systematic review and meta-analysis

PurposeIn light of the mounting prevalence of stress in contemporary society and the growing interest in stress reduction methods, this review investigates the potential of taiji as a viable strategy for alleviating stress.MethodsMEDLINE, EMBASE, the Cochrane Controlled Trials Register (CENTRAL), PsycINFO, and Web of Science were searched up to April 2023 to identify randomized controlled trials of taiji. Studies in both patients and healthy populations were considered. They had to provide a measure of perceived stress and include a no treatment or placebo control group. Data were extracted by two reviewers. Pooled standardized mean differences (SMD) were calculated for perceived stress, biological stress markers, anxiety, depression, and quality of life (QoL). Meta-regression analyses were performed to identify sources of heterogeneity.ResultsEleven trials with a total of 1323 patients comparing taiji to no intervention met the inclusion criteria. The included studies varied strongly with regard to patient characteristics, taiji intervention, and methodological quality. The overall SMD for perceived stress was significant at -0.41 (95% confidence interval, CI, -0.63 to -0.19; I2 = 63%). Exclusion of studies with less than 100 participants yielded a diminished SMD at -0.26 (95% CI, -0.45 to -0.06). The SMD for perceived stress at follow-up was significant (-0.25, 95% CI -0.46 to -0.05). Secondary outcomes highlighted improvements in anxiety and physical QoL, while depression, mental QoL, and biological stress markers remained unchanged.ConclusionsResults underscore taiji's potential in mitigating perceived stress in both patients and healthy populations, paralleled by enhancements in depressive symptoms, anxiety levels, and physical QoL.

Relationship between circadian rhythm and Malondialdehyde serum levels in acute and stabilized schizophrenic patients

IntroductionMalondialdehyde (MDA) is a product of polyunsaturated fatty acid peroxidation (Del Rio D, et al. A review of recent studies on MDA as toxic molecule and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis. 2005;15:316-28). It is a biomarker of oxidative stress and is involved in the pathophysiology of schizophrenia (Goh et al. Asian J Psychiatr. 2022;67:102932). Schizofrenia is linked to disrupted oxidative balance and inflammation (Więdłocha et al. Brain Sci. 2023;13:490). Prior research has shown connections between biomarkers and circadian rhythms in schizophrenia (Morera &amp; Abreu. Acta Physiol Scand. 2007;43:313-14) and diabetes type 2 (Kanabrocki EL, et al. Circadian variation in oxidative stress biomarkers in healthy and type II diabetic men. Chronobiol Int. 2002;19:423-39). To determinate if MDA levels have a role in schizophrenia and follow a circadian rhythm may be useful.ObjectivesThe aim of our study is to compare diurnal and nocturnal MDA serum levels in patients in acute and stabilized phases of schizophrenia according to CIE-10 to find out if there are variations related with circadian rhythmsMethods47 patients were included in our study in two clinical phases: acute episode and stabilization. Blood samples were collected at 12:00h and at 00:00h. MDA serum levels were measured twice: when patients were decompensated (admission) and at clinical stabilization (discharge). The relationship between quantitative variables at both times was analysed by T-Student testResultsThere is no significative difference between night and day MDA levels in the acute phase of the schizophrenia (2.22±1.352 vs. 1.93±1.530, p&lt;0.09). There is statistical significance between 12:00 and 00:00 (1.90±1.136 vs. 1.34±0.868, p&lt;0.001) at discharge: it was observed that levels decreased. This result can be interpreted as there is circadian rhythm in stabilized phases.Conclusions MDA levels in patients with schizophrenia do not follow a circadian rhythm in the acute episode. When they are clinically stabilized present a circadian change. These patients lose the circadian rhythm in acute episodes. MDA circadian rhythm may help diagnose the clinical phase and its severity. It is necessary to perform more studies to know its utility as an oxidative biomarkerDisclosure of InterestNone Declared

STRESS AND DEATH: GLUCOCORTICOIDS AND SURVIVAL IN A WILD PRIMATE MODEL OF AGING

Abstract Chronic exposure to stressors has been linked with a wide range of detrimental effects on health in humans, laboratory animals, and a few wild animal populations. Glucocorticoids (GCs) mediate stress responses, and consequently GC levels are regularly measured in humans and other animals as biological markers of stress. However, no tests in humans or in natural populations of animals have yet established clear connections between environmental stressors, chronically elevated GCs, and shortened lifespan. To fill this gap, we used longitudinal data on wild female baboons to investigate the relationship between GC levels and survival—the single greatest determinant of variation in evolutionary fitness among female baboons. Using 14,173 GC measurements from 242 wild adult female baboons over 1634 female years, we document a powerful link between GCs and survival: females with relatively high current GCs or high lifelong cumulative GCs face an elevated risk of death. A hypothetical female who maintained GCs in the top 90% for her age across adulthood would be expected to lose 5.4 years of life relative to a female who maintained GCs in the bottom 10% for her age. Hence, differences among individuals in HPA axis activity provide valuable prognostic information about disparities in lifespan. Together, our results both support the value of GCs as a window into health, fitness, and aging and suggest that they may mechanistically contribute to the established link between sociality and lifespan.

ASSOCIATIONS BETWEEN SENSE OF PURPOSE, NEGATIVE AFFECT, AND CORTISOL: EVIDENCE FROM REPEATED DAILY ASSESSMENTS

Abstract A growing literature suggests that having a sense of purpose in life is key to supporting optimal aging outcomes. One proposed mechanism for such benefits posits that having strong sense of purpose facilitates better management of and less reactivity to daily negative experiences, which over time may impact health. However, there remains a paucity of research investigating sense of purpose, affective experiences, and biological stress markers as individuals engage in their daily life routines. The present study sought to examine everyday associations between sense of purpose in life, negative affect, and salivary cortisol using repeated daily life assessments. A sample of 170 older adults aged 60 to 87 (M =71.18 years, SD=6.06) completed affect ratings and provided concurrent salivary cortisol samples 4 times per day over 7 consecutive days. Multilevel growth modeling was used to examine whether trait sense of purpose in life moderated within-day associations between negative affect and log-transformed cortisol levels (nmol/L), adjusting for relevant demographic information and factors that may impact cortisol (e.g., time since waking, caffeine intake). Analyses revealed that sense of purpose was indeed associated with lower daily negative affect, but it did not predict everyday cortisol and was also not moderating the within-person couplings between everyday negative affect and cortisol. Our results suggest that purpose in life shapes daily affect dynamics of older adults, yet not through modulating the physiological implications of negative affect. Follow-up analyses will explore whether these findings generalize to vulnerable groups of very old adults and those in poor health.

THE RELATIONSHIP BETWEEN ALLOSTATIC LOAD AND PROGRESS OF MULTIMORBIDITY AMONG OLDER AMERICANS

Abstract To examine the relationship between allostatic load and progress of multimorbidity over 10 years among older Americans and whether it mediates socioeconomic inequalities in multimorbidity. Methods Six Waves of Health and Retirement Study (HRS), a longitudinal survey of older American adults from 2006 -2016. Multimorbidity was indicated by 5 chronic conditions: diabetes, heart conditions, lung diseases, cancer, and stroke. Socioeconomic factors were education, total wealth, poverty-income ratio (income), and race/ethnicity. Behavioural factors were smoking, excessive alcohol consumption, physical activity, and body mass index (BMI). Allostatic load was used as a biomarker of stress and was indicated by a combination of total cholesterol, high-density lipoprotein, glycosylated hemoglobin, c-reactive protein, waist circumference, and high blood pressure. Two Multilevel mixed effects generalized linear models were constructed to assess the association between allostatic load and progress of multimorbidity and whether allostatic load explained socioeconomic inequalities in the progress of multimorbidity. All variables included in the analysis were time-varying except gender, race/ethnicity, and education. Results Allostatic load was significantly associated with the progress of multimorbidity even after adjusting for socioeconomic and behavioural factors with a rate ratio (RR) of 1.12 (95%CI: 1.11, 1.13). The association between socioeconomic factors and multimorbidity was slightly attenuated after adjusting for allostatic load. Socioeconomic factors were also associated with changes in allostatic load. Conclusion Biological markers of stress indicated by allostatic load were associated with the progress of multimorbidity. Allostatic load appears to be induced by adverse socioeconomic factors and mediates the relationship between socioeconomic factors and progress of multimorbidity.

Understanding the harmful effects of polyethylene microplastics on Eisenia fetida: A toxicological evaluation

Microplastics, measuring less than 5 mm, are pervasive environmental pollutants raising concerns about their toxic effects on terrestrial ecosystems, especially earthworms.A comprehensive toxicological evaluation of polyethylene microplastics on earthworms will be beneficial for determining the detrimental impacts of these ubiquitous pollutants on soil ecosystem. Therefore, in the present study, the best representative soil organism, earthworms (Eisenia fetida), were opted for examining the toxicological effect of polyethylene microplastic. E. fetida were subjected to different concentrations of polyethylene microplastic (200, 400, 600, 800, and 1000 mg/kg) in soil and randomly picked out on days 7 to 56. Earthworms exposed to higher concentration of polyethylene (1000 mg/kg of artificial soil) showed a significant reduction in body weight and cocoon formation after 35th days of incubation. A consistent decrease in the concentration of carbohydrates, lipids, and protein was observed when the worms were exposed to the higher concentration of polyethylene. Further, antioxidant enzymes like superoxide dismutase, glutathione S-transferase, peroxidase, catalase, and malondialdehyde were determined for antioxidant stress.Exposure of 200 mg/kg to 1000 mg/kg of artificial soil caused a prominent amplification in the build-up of malonedialdehyde (a biological marker of oxidative stress) by 1.29-fold. It also considerably augmented the activity of the antioxidant enzymes viz., glutathione S-transferase (1.54-fold), superoxide dismutase (1.51-fold), peroxidase (1.25-fold), and catalase (1.87-fold). The present study's findings provide a new understanding of the toxic effect of microplastic on earthworm E. fetida, presenting a foundation for its risk evaluation on soil ecosystems and non-target biological toxicity.

A Biomarker of Stress and Self-reported Caregiving Distress Predict Poor Quality of Life in Family Caregivers of Patients With Heart Failure.

Family caregivers are at a high risk for low quality of life due to caregiving-related stress. Caregivers' stress is commonly assessed using self-reported measures, which reflect relatively subjective and long-term stress related to caregiving, but objective biological markers of stress are rarely used for caregivers. The purposes of this study were (1) to determine whether caregiver characteristics were associated with stress assessed using a stress biomarker (serum cortisol) and a self-reported caregiving distress measure (Caregiver Burden Inventory) and (2) to determine the predictability of both stress measures for quality of life in caregivers of patients with heart failure. Taiwanese family caregivers (N = 113; mean age, 54.5 years; 70.8% female) of patients with heart failure completed surveys including caregiving distress and quality of life measured by the Caregiver Burden Inventory and the Short Form-36 (physical and psychological well-being subscales), respectively, and provided blood samples for serum cortisol. Independent t tests, correlation, and hierarchical regression were conducted. Single caregivers had higher serum cortisol levels than married caregivers (P = .002). Men had significantly higher serum cortisol levels than women (P = .010), but men reported lower caregiving distress than women (P = .049). Both serum cortisol (β = -0.32, P = .012) and caregiving distress (β = -0.29, P = .018) were significant predictors of quality of life in the physical well-being scale while controlling for caregivers' characteristics and depressive symptoms. Serum cortisol (β = -0.28, P = .026) and caregiving distress (β = -0.25, P = .027) also predicted quality of life in the psychological well-being scale. Serum cortisol and self-reported caregiving distress have similar predictability for quality of life in family caregivers of patients with heart failure. Reducing stress and caregiving distress is critical to improving quality of life in this population.

Self-Administered Gentle Yoga and Yoga Breathing Intervention Improves Burden and Stress Biomarkers in Caregivers of Persons Living with Dementia.

Family caregivers of adults with Alzheimer's disease and related dementias (ADRD) are the fastest growing group of informal healthcare providers in the United States. These individuals experience high levels of stress and physical and psychosocial symptoms related to their caregiving role. We provided 20 ADRD caregivers (≥ 55 years of age) with training and access to a mobile health app for at-home practice of gentle yoga and yoga breathing exercises. Here, we report secondary outcomes, including changes in caregiver physical and mental function, burden, fatigue, sleep, and biological stress markers (salivary cortisol and 1,5-anhydroglucitol [1,5-AG] assays) from Baseline (Week 1) to Study End (Week 12). Self-reported questionnaire data were collected online via the Research Electronic Data Capture system, and biomarker data were collected via saliva samples. Results supported indications for slight improvement in outcomes of caregiving burden among ADRD caregivers using the gentle yoga and yoga breathing app. Furthermore, slight improvements in mental health were observed; the greatest gains were made by those reporting higher burden and having family members with more severe dementias. Findings indicate that those experiencing the greatest improvement in caregiver burden scores spent the most time doing gentle yoga and yoga breathing exercises. Salivary stress biomarkers moved in a favorable direction (decreased cortisol; increased 1,5-AG) among caregivers practicing the exercises most often. This is among the first studies of gentle yoga and yoga breathing exercises for relieving ADRD caregiver burden and the first we are aware of to incorporate stress biomarker measurement.

The Cytotoxic Effect of Septic Plasma on Healthy RBCs: Is Eryptosis a New Mechanism for Sepsis?

Sepsis is a life-threatening multiple-organ dysfunction induced by infection and is one of the leading causes of mortality and critical illness worldwide. The pathogenesis of sepsis involves the alteration of several biochemical pathways such as immune response, coagulation, dysfunction of endothelium and tissue damage through cellular death and/or apoptosis. Recently, in vitro and in vivo studies reported changes in the morphology and in the shape of human red blood cells (RBCs) causing erythrocyte death (eryptosis) during sepsis. Characteristics of eryptosis include cell shrinkage, membrane blebbing, and surface exposure to phosphatidylserine (PS), which attract macrophages. The aim of this study was to evaluate the in vitro induction of eryptosis on healthy RBCs exposed to septic plasma at different time points. Furthermore, we preliminary investigated the in vivo levels of eryptosis in septic patients and its relationship with Endotoxin Activity Assay (EAA), mortality and other biological markers of inflammation and oxidative stress. We enrolled 16 septic patients and 16 healthy subjects (no systemic inflammation in the last 3 months) as a control group. At diagnosis, we measured Interleukin-6 (IL-6) and Myeloperoxidase (MPO). For in vitro study, healthy RBCs were exposed to the plasma of septic patients and CTR for 15 min, 1, 2, 4 and 24 h. Morphological markers of death and eryptosis were evaluated by flow cytometric analyses. The cytotoxic effect of septic plasma on RBCs was studied in vitro at 15 min, 1, 2, 4 and 24 h. Healthy RBCs incubated with plasma from septic patients went through significant morphological changes and eryptosis compared to those exposed to plasma from the control group at all time points (all, p < 0.001). IL-6 and MPO levels were significantly higher in septic patients than in controls (both, p < 0.001). The percentage of AnnexinV-binding RBCs was significantly higher in septic patients with EAA level ≥0.60 (positive EAA: 32.4%, IQR 27.6-36.2) compared to septic patients with EAA level <0.60 (negative EAA: 14.7%, IQR 5.7-30.7) (p = 0.04). Significant correlations were observed between eryptosis and EAA levels (Spearman rho2 = 0.50, p < 0.05), IL-6 (Spearman rho2 = 0.61, p < 0.05) and MPO (Spearman rho2 = 0.70, p < 0.05). In conclusion, we observed a quick and great cytotoxic effect of septic plasma on healthy RBCs and a strong correlation with other biomarkers of severity of sepsis. Based on these results, we confirmed the pathological role of eryptosis in sepsis and we hypothesized its use as a biomarker of sepsis, potentially helping physicians to face important treatment decisions.

Comparative Assessment of Salivary Level of Cortisol, Anxiety and Depression in Patients with Oral Conditions: A Case Control Study

Introduction: Cortisol, as the main human glucocorticoid, is considered to be a biological marker of stress and anxiety. It is suggested that stress with its presumed effects on the immune system, constitutes one of the major causative agents for oral mucosal alterations. Methodology: To enable the study of gender-based differences in stress, salivary alpha-amylase levels and oral lesions, an equal gender distribution was guaranteed. The individuals were then given a clinical examination to look for oral mucosal alterations caused by stress, such as recurrent aphthous ulcers, oral lichen planus, dry mouth and burning mouth syndrome. To identify Temporomandibular Joint Disorders (TMDs), which are also linked to stress, trigger points, masticatory muscles and TMJs were examined. Results: 80 participants made up the research team, ranging in age from 24-47 years for the experimental group and 27-50 years for the control group. There was an equal number of men and women in both groups. The investigation group’s average age was 33.70 years, compared to 31.93 years for the control group (p=0.16). The study group’s female participants exhibited stress levels that ranged from 5% (N=1) for light stress to 40% (N=8) for severe stress (p=0.10). Conclusion: However, there was no connection between oral alterations and salivary alpha-amylase.