Markers Of Stress Response Research Articles

Peripheral Markers of Stress Response Across the Spectrum of Suicidal Thoughts and Behavior

HPA axis dysregulation is associated with 4.5-fold increased risk for suicide. It is not clear whether HPA axis dysregulation exists prior to suicidal behavior or is a consequence of an attempt. Until recently, the assessment of HPA axis activity prior to suicidal behavior would have been impossible. The analysis of hair cortisol concentrations (HCC) provides a retrospective assessment of cortisol secretion over the past few months.

EFFECT OF TRANSCRIPTION FACTOR MODULATORS ON CARBOHYDRATES AND LIPID METABOLISM IN RATS AFTER LAPARATOMY UNDER LIPOPOLYSACCHARIDE-INDUCED SYSTEMIC INFLAMMATORY RESPONSE

This study is devoted to investigating the effect of NF-κB and Nrf2, transcription factor modulators, on markers of surgical stress and acute phase response, carbohydrate and lipid metabolism in the case of abdominal surgical trauma (laparotomy) under lipopolysaccharide (LPS)-induced systemic inflammatory response (SIR). The study was performed on 28 white Wistar male rats weighing 220-250 g, divided into 4 groups: 1st (control) included "pseudo-operated" animals; 2nd group involved rats, who underwent laparotomy following the LPS-induced SIR modelling; the animals of the 3rd, 4th and 5th groups subjected to laparotomy following LPS-induced SIR then for 7 days received ammonium pyrrolidinedithiocarbamate, an NF-κB activation inhibitor, in a dose of 76 mg/kg, dimethyl fumarate, an N inducer, in a dose of 15 mg / kg in 10% dimethyl sulfoxide solution, and a water-soluble form of quercetin in a dose of 100 mg/kg that is 10 mg/kg in terms of quercetin. The measurements were carried out in 7 days after the false surgical operation or laparotomy. It has been found out that the use of ammonium pyrrolidine dithiocarbamate, dimethyl fumarate, and water-soluble form of quercetin under the combined effects of surgical trauma (laparotomy) and S. typhi LPS significantly reduces the concentration of cortisol in blood plasma and the content of ceruloplasmin in the blood serum, lowers the level of hyperglycemia and hypertriacylglycerolemia.

Effects of heat stress on cyto(chemo)kine and inflammasome gene expression and mechanical properties in isolated red and white blood cells from 4 commercial broiler lines and their ancestor jungle fowl

Commercial broilers have been selected for high growth rate and productivity; however, this has negatively impacted their susceptibility to heat stress (HS). Insight into the molecular mechanisms underlying this vulnerability can help design targeted strategies for improvement of HS tolerance. Red blood cells (RBC) and white blood cells (WBC) were isolated from red jungle fowl and 4 lines of commercial modern broilers. Lines A and B are considered standard-yielding lines, whereas Lines C and D are high-yielding. Cells were cultured at either 37°C or 45°C for 2 h to induce heat stress (HS). Gene expression of cytokines, chemokines, and inflammasome components were measured. Heat shock proteins 27 and 70 (HSPs) in RBC were significantly affected by line (P < 0.05), whereas HSP27 and 60 were affected by temperature (P < 0.05). In WBC, there was a significant line effect on HSP gene expression (P < 0.05), and a significant increase (P < 0.05) in HSP90 in Line D in HS compared to TN conditions. In RBC, there was a main effect of HS on TNFα, CCL4, and CCLL4 (P < 0.05). HS significantly increased IL-8L1 (>30-fold, P < 0.0001) in Line C. Inflammasome genes (NLRP3, NLRC5 and NLRC3) were significantly affected by the line studied (P < 0.05). In WBC, the effect of line was significant for all cytokines, chemokines, and inflammasome components studied (P < 0.05). To examine the mechanical properties of isolated RBC from the 4 commercial lines and jungle fowl, RBC were placed into nematic liquid crystals, where Lines B and D were the most strained, and Line A and the jungle fowl were the least strained. Together, these findings indicate not only the dynamic nature of circulating cells, but the differences in the stress and inflammatory response among commercially available lines and their common ancestor. These profiles have the potential to serve as a future marker for stress responses in broilers, though further study is warranted.

Impact of nitrate addition on the resistome and mobilome from a full-scale sewer

Oxidative chemicals, such as nitrate, are periodically added to sewer systems to mitigate sulfide production and its accumulation but data are lacking on how these treatments affect sewage microbiota and alter their gene expression and mobilization. The present study investigated such effects on the biofilm of a full-scale sewer collected at two different locations, namely a pumping station and at the inlet of an urban wastewater treatment plant (WWTP), before and 15 days after nitrate dosage using a combination of culture-dependent and -independent approaches. Nitrate dosing resulted ineffective on the concentration of antibiotic-resistant Escherichia coli (AR-EC) in biofilms but greatly affected the composition of biofilm bacterial communities and the associated resistome and mobilome, especially at the pumping station where nitrate was dosed. Such responses consisted of a clear reduction on strict anaerobes; an almost twofold increase on the expression of recA gene (stress-response marker); and a significant increase on the relative abundance of most antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs). In turn, the effects of nitrate dosing at the WWTP inlet were barely visible, suggesting that they vanished into the distance from the pumping site (2.4 km). Remarkably, however, the relative abundance of both resistance and mobilization gene biomarkers at the inlet of the studied WWTP clearly oversized that at the pumping station confirming that these facilities are sinks where these resistance determinants accumulate and propagate. Considering the abundance of resistant bacteria and genes in urban sewage, the effects of dosing chemicals should be carefully assessed to lessen the load of such biological pollutants into WWTPs.

My Life in HRV Biofeedback Research.

This paper reviews the published work of me along with my students and close colleagues on the topic of heart rate variability biofeedback (HRVB). It includes early research by Vaschillo documenting resonance characteristics of the baroreflex system that causes large oscillations in heart rate when breathing at resonance frequency, research on heart rate variability as a marker of parasympathetic stress response in asthma, and HRVB as a treatment for asthma and depression. Many questions about HRVB remain unresolved, and important questions for future research are listed.

Oxidative damage and mitochondrial functionality in hearts from KO UCP3 mice housed at thermoneutrality.

The antioxidant role of mitochondrial uncoupling protein 3 (UCP3) is controversial. This work aimed to investigate the effects of UCP3 on the heart of mice housed at thermoneutral temperature, an experimental condition that avoids the effects of thermoregulation on mitochondrial activity and redox homeostasis, preventing the alterations related to these processes from confusing the results caused by the lack of UCP3. WT and KO UCP3 mice were acclimatized at 30°C for 4weeks and hearts were used to evaluate metabolic capacity and redox state. Tissue and mitochondrial respiration, the activities of the mitochondrial complexes, and the protein expression of mitochondrial complexes markers furnished information on mitochondrial functionality. The levels of lipid and protein oxidative damage markers, the activity of antioxidant enzymes, the reactive oxygen species levels, and the susceptibility to in vitro Fe-ascorbate-induced oxidative stress furnished information on redox state. UCP3 ablation reduced tissue and mitochondrial respiratory capacities, not affecting the mitochondrial content. In KO UCP3 mice, the mitochondrial complexes activities were lower than in WT without changes in their content. These effects were accompanied by an increase in the level of oxidative stress markers, ROS content, and in vitro susceptibility to oxidative stress, notwithstanding that the activities of antioxidant enzymes were not affected by UCP3 ablation. Such modifications are also associated with enhanced activation/phosphorylation of EIF2α, a marker of integrated stress response and endoplasmic reticulum stress (GRP778 BIP). The lack of UCP3 makes the heart more prone to oxidative insult by reducing oxygen consumption and increasing ROS. Our results demonstrate that UCP3 helps the cell to preserve mitochondrial function by mitigating oxidative stress.

Gradual increase of temperature trigger metabolic and oxidative responses in plasma and body tissues in the Antarctic fish Notothenia rossii.

Antarctica is considered a thermally stable ecosystem; however, climate studies point to increases in water temperatures in this region. These thermal changes may affect the biological processes and promote metabolic changes in the adapted organisms that live in this region, rendering the animals more vulnerable to oxidative damage. This study assessed the effect of acclimation temperature on the levels of stress response markers in plasma, kidney, gill, liver, and brain tissues of Notothenia rossii subjected to gradual temperature changes of 0.5°C/day until reaching temperatures of 2, 4, 6, and 8°C. Under the effect of the 0.5°C/day acclimation rate, gill tissue showed increased glutathione-S-transferase (GST) activity; kidney tissue showed increased H+-ATPase activity. In the liver, there was also an increase in GSH. In plasma, gradual decreases in the concentrations of total proteins and globulins were observed. These responses indicate a higher production of reactive oxygen species ROS, an imbalance in energy demand, and a lack in protein synthesis. Gradual increase in temperature may cause opposite responses to the thermal shock model in N. rossii.

Age-related neuronal damage by advanced glycation end products through altered proteostasis

Aging is a main risk factor for many diseases including neurodegenerative disorders. Numerous theories and mechanisms including accumulation of advanced glycation end products (AGEs) have been put forward in explaining brain aging. However, a focused study on the status of AGEs in the brain during progressive aging in connection with interrelated cellular processes like ubiquitin-proteasome system (UPS), unfolded protein response, autophagy-lysosome system and apoptosis is lacking. In this study, we investigated the levels of AGEs in the brain of 5-, 10-, 15- and 20-months old WNIN rats. Endoplasmic reticulum (ER) stress response, UPS components, autophagy flux, neurotrophic and presynaptic markers along with cell death markers were analyzed by immunoblotting. The neuronal architecture was analyzed by H&E and Nissl staining. The results demonstrated progressive accumulation of AGEs in the brain during aging. Adaptive ER stress response was observed by 10-months while maladaptive ER stress response was seen at 15- and 20-months of age along with impaired UPS and autophagy, and perturbations in neuronal growth factors. All these disturbances intensify with age to further exaggerate cell death mechanisms. There was a shrinkage of the cell size with aging and Congo-red staining revealed β-amyloid accumulation in higher ages. Together these results suggest that progressive accumulation of AGEs with aging in the brain may lead to neuronal damage by affecting ER homeostasis, UPS, autophagic flux, and neuronal growth factors.

Sex Differences in Behavior and Molecular Pathology in the 5XFAD Model.

The prevalence of Alzheimer's disease (AD) is greater in women compared to men, but the reasons for this remain unknown. This sex difference has been widely neglected in experimental studies using transgenic mouse models ofAD. Here, we studied behavior and molecular pathology of 5-month-old 5XFAD mice, which express mutated human amyloid precursor protein and presenilin-1 on a C57BL/6J background, versus their wild-type littermate controls, to compare both sex- and genotype-dependent differences. A novel behavioral paradigm was utilized (OF-NO-SI), comprising activity measures (Open Field, OF) arena, followed by Novel Object exploration (NO) and Social Interaction (SI) of a sex-matched conspecific. Each segment consisted of two repeated trials to assess between-trial habituation. Subsequently, brain pathology (amyloid load, stress response and inflammation markers, synaptic integrity, trophic support) was assessed using qPCR and western blotting. Female 5XFAD mice had higher levels of human APP and amyloid-β and heightened inflammation versus males. These markers correlated with hyperactivity observed in both sexes, yet only female 5XFAD mice presented with subtle deficits in object and social exploration. Male animals had higher expression of stress markers and neurotrophic factors irrespective of genotype, this correlated with cognitive performance. The impact of sex on AD-relevant phenotypes is in line with human data and emphasizes the necessity of appropriate study design and reporting. Differential molecular profiles observed in male versus female mice offer insights into possible protective mechanisms, and hence treatment strategies.

Инклюзия против стресса: высшее образование для представителей коренных народов России

This article problematizes the organization of higher education for indigenous minorities, considering alternative strategies, namely segregation and inclusion, at the theoretical and empirical levels. Based on the analysis of publications by Russian and foreign researchers, representatives of indigenous peoples are presented as one of the categories, along with students from remote regions and from families with low socioeconomic status, whose opportunities for higher education are limited by a number of economic and social factors. The empirical study focuses on a group of Komi-Permyak (one of the indigenous ethnic groups of the Russian North) students studying in a large industrial city, Perm. The Department of Komi-Permyak Language and Literature of the Faculty of Philology at the Perm State University of Humanities and Pedagogy (PSUHP) provides professional training for teachers majoring in “Native (Komi-Permyak) Language and Literature and the Russian Language”. In addition to pedagogical disciplines, the curriculum includes a wide range of disciplines related to the linguistic aspects of the Komi-Permyak language, literature and regional studies. In the course of the interdisciplinary study, indicators of cortisol and anxiety levels -markers of stress response - were obtained. Their comparison with the same indicators of Russian students of other faculties of the same university (N=268) allowed us to conclude that Komi-Permyak students are adapted to the learn- © Козлова М.А., Козлов А.И., Корниенко Д.С., 2022 ing conditions. This fact distinguishes this group from students from other ethnic minorities of the Arctic and subarctic regions who study at other universities. The data provided by the department's administration on the composition of students indicate a low dropout rate of Komi-Permyaks, which indicates that the main factor of educational inequality in relation to this category of students has been overcome. The second stage of the study, carried out in a qualitative methodology (semi-structured interviews, N=9), analyzed aspects of the biographical situation, including migration experience, features of the organization of the educational process and individual strategies of education-al/career formation and building social ties within and outside the ethno-cultural community. Based on the barriers identified in the narratives of the informants and new opportunities for integration into a new sociocultural environment, the key factors of successful adaptation of indigenous students to learning conditions are reconstructed. On the basis of the obtained data, a conclusion is made about the adaptive and integrative potential of soft strategies of educational inclusion, which involve the creation of conditions that allow an individual to independently vary the degree of cultural closeness-openness and social inclusion-exclusion.

Salivary Alpha-Amylase Activity and Mild Cognitive Impairment among Japanese Older Adults: The Toon Health Study.

There is growing interest in examining objective markers for early identification and behavioral intervention to prevent dementia and mild cognitive impairment in clinical and community settings. To investigate the association between salivary alpha-amylase as an objective measure of psychological stress response and mild cognitive impairment for the implication of psychological stress in the development of mild cognitive impairment. This cross-sectional study involved 865 participants aged ≥ 65 years. A saliva sample was collected in the morning, and the levels of salivary alpha-amylase were assayed. Mild cognitive impairment was evaluated using the Japanese version of the Montreal Cognitive Assessment; a score < 26 was indicative of mild cognitive impairment. A multivariable logistic regression model was used to examine the association of salivary alpha-amylase and mild cognitive impairment after adjusting for age, sex, current drinking status, current smoking status, body mass index, hypertension, diabetes mellitus, physical activity, education, social support, social network, and heart rate variability. Salivary alpha-amylase was associated with mild cognitive impairment (the multivariable-adjusted odds ratio [95% confidence interval] for the 1-standard deviation increment of log-transformed salivary alpha-amylase was 1.24 [1.07-1.44]). This significant association persisted after adjusting for various confounding factors. Elevation of salivary alpha-amylase was associated with mild cognitive impairment among Japanese community-dwelling older adults. This suggests that salivary alpha-amylase is a useful objective marker of psychological stress responses associated with mild cognitive impairment.

Retrospective analysis of remifentanil combined with dexmedetomidine intravenous anesthesia combined with brachial plexus block on shoulder arthroscopic surgery in elderly patients.

Objectives:To analyze the effect of remifentanil combined with dexmedetomidine intravenous anesthesia combined with brachial plexus block on shoulder arthroscopic surgery in elderly patients.Methods:This retrospective study conducted at Jiading Branch of Shanghai General Hospital, investigated clinical data from elderly patients receiving shoulder arthroscopy between January 2020 and June 2021. Based on the treatment, patients were retrospectively divided into Group-I (remifentanil combined with dexmedetomidine) and Group-II (remifentanil continuous pump injection). Hemodynamic indices, such as mean arterial pressure (MAP) and heart rate (HR), degree of pain (VAS score), and stress response marker levels were examined prior to the operation and at various time points post-operation. Operation time and adverse reaction incidences were also evaluated.Results:There was no significant differences in MAP and HR between the two groups prior to the operation. However, MAP and HR levels were lower in Group-I patients at three time points post-operation. Similarly, VAS scores were not different between the two groups prior to the operation but were much lower in Group-I at multiple time points post-operation. The same trend was observed for the stress-induced angiotensin-II, cortisol, and aldosterone. Additionally, patients in Group-I had lower incidence of adverse reactions and shorter operation time.Conclusion:Remifentanil combined with dexmedetomidine intravenous anesthesia for shoulder arthroscopic surgery under general anesthesia combined with brachial plexus block in elderly patients can maintain hemodynamic stability, shorten operation time, reduce the degree of stress reaction, pain caused by invasive operation, and reduce the incidence of adverse reactions.

Perceived chronic stress influences the effect of acute stress on cognitive flexibility

Executive functions are cognitive processes that facilitate goal-directed behavior by enabling us to direct and control our thoughts. Cognitive flexibility is an executive function characterized by the ability to mentally shift between rules, strategies, or tasks. Several studies have reported that acute (brief) stress impairs cognitive flexibility. Even though an individual’s perception of their chronic stress levels is shown to influence effects of future stressors, the interactive effect of acute and perceived chronic stress on cognitive flexibility is not known. We conducted two experiments to address this gap. In both studies, perceived chronic stress was measured using the Perceived Stress Scale. Acute stress was induced using the Cold Pressor Test. Number of perseverative errors on the Wisconsin Card Sorting Test was used as an indicator of cognitive flexibility. In Study 2, we also measured salivary alpha amylase as a marker of the physiological stress response. Data from our two studies are consistent with the hypothesis that an individual’s perception of their chronic stress level may impact the effect of acute stress on perseveration. In Study 1, we observed a significant interaction between acute and perceived chronic stress on perseverative errors, such that only individuals who reported high levels of perceived chronic stress prior to acute stress exposure showed no change in perseveration following the acute stress manipulation. This effect did not differ based on participant sex. In Study 2, we found a similar interaction effect of acute and perceived chronic stress on perseverative errors in an all-woman sample. After identifying salivary alpha amylase responders and non-responders, we observed a strong, negative correlation between perceived chronic stress and perseverative errors amongst the responders only. Our data highlight the value in studying salivary alpha amylase in response to acute stress exposure. Additionally, perceived chronic stress emerged as a key variable in the relationship between acute stress and cognitive flexibility. Overall, our work suggests that future research interested in interrogating moderators in the relationship between acute stress and cognition would benefit from inclusion of measures of chronic stress.

Associations between neuropsychiatric symptoms, white matter microstructural integrity, and diagnostic status in the spectrum of Alzheimer’s disease

AbstractBackgroundRecent studies have found that individuals who have undergone psychological stress and/or are affected by a chronic stress‐related disorder have an increased risk of developing Alzheimer’s Disease (AD). However, currently the biological mechanism underlying this relationship remains elusive. We hypothesized that white matter integrity loss may be a potential mediator between psychological stress and the development of AD. The goal of this study was to examine the relationship between neuropsychiatric symptoms as a proxy of stress responses, white matter microstructural integrity, and diagnostic status along the spectrum of AD.MethodWe evaluated the relationship between neuropsychiatric symptoms, white matter microstructural integrity, and diagnostic status along the spectrum of AD in 133 participants (ages 55.2‐90.4 years) selected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI‐2). Total scores in a brief Neuropsychiatric Inventory Questionnaire (NPI‐Q) were used to represent individuals’ psychological stress responses. We quantified white matter integrity measures using diffusion tensor imaging scans processed by the FMRIB's Diffusion Toolbox followed by the FSL Tract‐Based Spatial Statistics toolbox.ResultNPI‐Q scores representing stress responses significantly differed across diagnostic groups. Specifically, patients with AD (N=40, mean age=74.39) showed significantly higher NPI‐Q scores compared with cognitively normal (CN) older adults (N=44, mean age=73.39) and patients with Mild Cognitive Impairment (MCI)(N=49, mean age=75.64). Whole brain voxel‐wise analyses with white matter integrity measures as quantified as fractional anisotropy (FA) and mean diffusivity (MD) showed significant FA and MD differences (p ≤ 0.01) in the splenium, cingulum, superior longitudinal fasciculus, posterior thalamic radiation and the corpus callosum regions when controlling for age and sex. These differences were greater for AD patients compared with CN participants than those with MCI. NPI‐Q scores, however, were not related to a degree of white matter integrity in this sample.ConclusionSignificant group differences are shown in stress responses and white matter integrity across the diagnostic groups in the AD spectrum, which is consistent with the literature. Future studies are warranted to integrate reliable biological markers of stress responses to assess the impact of stress responses on microstructural changes and AD pathologies.

Exercise-Induced Adrenocorticotropic Hormone Response Is Cooperatively Regulated by Hypothalamic Arginine Vasopressin and Corticotrophin-Releasing Hormone

Introduction: Exercise becomes a stress when performed at an intensity above the lactate threshold (LT) because at that point the plasma adrenocorticotropic hormone (ACTH), a marker of stress response, increases. It is possible that the exercise-induced ACTH response is regulated at least by arginine vasopressin (AVP) and possibly by corticotropin-releasing hormone (CRH), but this remains unclear. To clarify the involvement of these factors, it is useful to intervene pharmacologically in the regulatory mechanisms, with a physiologically acceptable exercise model. Methods: We used a special stress model of treadmill running (aerobic exercise) for male Wistar rats, which mimic the human physiological response, where plasma ACTH levels increase at just above the LT for 30 min. Animals were administered the AVP V_1b receptor antagonist SSR149415 (SSR) and/or the CRH type 1 receptor antagonist CP154526 (CP) intraperitoneally before the exercise, which allowed the monitoring of exercise-induced ACTH response. Immunohistochemical evaluation of activated AVP and CRH neurons with exercise was performed for the animals’ hypothalami. Results: A single injection of either antagonist, SSR or CP, resulted in inhibited ACTH levels after exercise stress. Moreover, the combined injection of SSR and CP strongly suppressed ACTH secretion during treadmill running to a greater extent than each alone. The running-exercise-induced activation of both AVP and CRH neurons in the hypothalamus was also confirmed. Conclusion: These results lead us to hypothesize that AVP and CRH are cooperatively involved in exercise-induced ACTH response just above the LT. This may also reflect the stress response with moderate-intensity exercise in humans.

Stress response markers in the blood of São Tomé green sea turtles (Chelonia mydas) and their relation with accumulated metal levels

Metals are persistent worldwide being harmful for diverse organisms and having complex and combined effects with other contaminants in the environment. Sea turtles accumulate these contaminants being considered good bioindicator species for marine pollution. However, very little is known on how this is affecting these charismatic animals. São Tomé and Príncipe archipelago harbours important green sea turtle (Chelonia mydas) nesting and feeding grounds. The main goal of this study was to determine metal and metalloid accumulation in the blood of females C. mydas nesting in São Tomé Island, and evaluate the possible impacts of this contamination by addressing molecular stress responses. Gene expression analysis was performed in blood targeting genes involved in detoxification/sequestration and metal transport (mt, mtf and fer), and in antioxidant and oxidative stress responses (cat, sod, gr, tdx, txrd, selp and gclc). Micronuclei analysis in blood was also addressed as a biomarker of genotoxicity. Present results showed significant correlations between different gene expressions with the metals evaluated. The best GLM models and significant relationships were found for mt expression, for which 78% of the variability was attributed to metal levels (Al, Cu, Fe, Hg, Pb and Zn), followed by micronuclei count (65% - Cr, Cu, Fe, Hg, Mn and Zn), tdx expression (52% - Cd, Fe, Mn, Pb and Se), and cat expression (52% - As, Fe, Se and Cd x Hg). Overall, this study demonstrates that these green sea turtles are trying to adapt to the oxidative stress and damage produced by metals through the increased expression of antioxidants and other protectors, which raises concerns about the impacts on these endangered organisms' fitness. Furthermore, promising biomarker candidates associated to metal stress were identified in this species that may be used in future biomonitoring studies using C. mydas’ blood, allowing for a temporal follow-up of the organisms.

Endoplasmic reticulum stress promotes local immunoglobulin E production in allergic rhinitis.

BackgroundThe role of endoplasmic reticulum (ER) stress in the pathogenesis of allergic rhinitis (AR) remains elusive.MethodsReal‐time polymerase chain reaction (RT‐PCR), immunohistochemistry, and western blotting analyses were performed to detect the expression of ER stress and unfolded protein response markers: 78‐kDa glucose‐regulated protein (GRP78), C/EBP homologous protein (CHOP), activating transcription factor 6 (ATF6α), spliced X‐box binding protein 1 (sXBP‐1), and phosphorylated eukaryotic initiation factor 2α (p‐eIF2α), in inferior turbinate tissue samples from patients with AR and non‐AR controls. Nasal tissues from patients with AR were cultured ex vivo and treated with 4‐phenylbutyric acid (4‐PBA), an ER stress inhibitor.ResultsCompared to those in non‐AR controls, the mRNA and protein levels of GRP78, CHOP, ATF6α, sXBP‐1, and p‐eIF2α were significantly increased in nasal tissues from patients with AR. GRP78 and CHOP were mainly expressed in CD138+ plasma cells in nasal tissues from patients with AR. The frequency of IgE+CD138+ plasma cells was significantly higher in nasal tissues from patients with AR than that in non‐AR controls. IgE levels in nasal secretions and tissues were positively correlated with GRP78 and CHOP mRNA levels in the nasal tissues. After 4‐PBA treatment, the protein expression of GRP78, CHOP, ATF6α, sXBP‐1, and p‐eIF2α was significantly reduced in cultured AR‐derived nasal tissues, and IgE levels were simultaneously decreased in cultured supernatants.ConclusionsER stress may be involved in the regulation of local IgE production in patients with AR. Inhibition of ER stress potentially provides a therapeutic avenue in AR by reducing local IgE production.Level of EvidenceNA

Of Whales and Genes: Unraveling the Physiological Response to Stressors in Belugas (Delphinapterus leucas) at the Molecular Level

Marine mammals, now more than ever, are exposed to environmental and anthropogenic stressors. A better understanding of stress physiology in marine mammals is warranted in order to assist in conservation efforts. This study screened gene expression profiles (cytokines, stress-response markers) in blood samples collected opportunistically under controlled conditions from aquarium belugas during transport and introduction to a novel environment (T/NEnv), participation in out-of-water examinations (OWE) and from wild belugas during live capture–release health assessments (WLCR). Quantitative-PCR was used to measure gene expression involved in physiological and immune responses at different time scales. Linear mixed models with repeated measures and pairwise comparisons were used for analysis. Overall, a generalized down-regulation of relative gene expression when compared to samples collected under behavioral control from aquarium whales or to pre-assessment samples of wild whales was observed, with genes IFNγ, IL2, TGFβ and Nr3c1 displaying the largest significant (p &lt; 0.05) changes. Significant (p &lt; 0.05) negative associations of inflammatory gene expression with norepinephrine suggest inhibitory effects of catecholamines on the inflammatory response. Overall, this study contributes to our understanding of the physiological response to stressors at the molecular level in belugas, and the genes suggested here can further be utilized as additional tools in beluga health assessments and monitoring.

Increased Impact of Air Pollution on Lung Function in Preterm versus Term Infants: The BILD Study.

Rationale: Infants born prematurely have impaired capacity to deal with oxidative stress shortly after birth. Objectives: We hypothesize that the relative impact of exposure to air pollution on lung function is higher in preterm than in term infants. Methods: In the prospective BILD (Basel-Bern Infant Lung Development) birth cohort of 254 preterm and 517 term infants, we investigated associations of particulate matter ⩽10 μm in aerodynamic diameter (PM10) and nitrogen dioxide with lung function at 44 weeks' postconceptional age and exhaled markers of inflammation and oxidative stress response (fractional exhaled nitric oxide [FeNO]) in an explorative hypothesis-driven study design. Multilevel mixed-effects models were used and adjusted for known confounders. Measurements and Main Results: Significant associations of PM10 during the second trimester of pregnancy with lung function and FeNO were found in term and preterm infants. Importantly, we observed stronger positive associations in preterm infants (born 32-36 wk), with an increase of 184.9 (95% confidence interval [CI], 79.1-290.7) ml/min [Formula: see text]e per 10-μg/m3 increase in PM10, than in term infants (75.3; 95% CI, 19.7-130.8 ml/min) (pprematurity × PM10 interaction = 0.04, after multiple comparison adjustment padj = 0.09). Associations of PM10 and FeNO differed between moderate to late preterm (3.4; 95% CI, -0.1 to 6.8 ppb) and term (-0.3; 95% CI, -1.5 to 0.9 ppb) infants, and the interaction with prematurity was significant (pprematurity × PM10 interaction = 0.006, padj = 0.036). Conclusions: Preterm infants showed significantly higher susceptibility even to low to moderate prenatal air pollution exposure than term infants, leading to increased impairment of postnatal lung function. FeNO results further elucidate differences in inflammatory/oxidative stress response when comparing preterm infants with term infants.

Bicyclist Stress Perceptions and Heart Rate Variability

This paper describes the relationship between a physiological marker of stress (heart rate variability) and survey-based stress responses from a cross-over real-world bicycling experiment. The analysis shows that while heart rate variability was inversely associated with survey-based estimates of stress, large uncertainty in the relationship indicates carefully controlled experiments are still needed before we can be confident that bicyclist stress can be measured through heart rate variability.