Stress-related Conditions Research Articles

Hydrogen Gas Inhalation Attenuates Acute Impulse Noise Trauma: A Preclinical In Vivo Study.

Molecular hydrogen (H2) has shown therapeutic potential in several oxidative stress-related conditions in humans, is well-tolerated, and is easily administered via inhalation.The aim of this preclinical in vivo study was to investigate whether impulse noise trauma can be prevented by H2 when inhaled immediately after impulse noise exposure. Guinea pigs (n = 26) were subjected to impulse noise (n = 400; 156 dB SPL; 0.33/s; n = 11; the Noise group), to impulse noise immediately followed by H2 inhalation (2 mol%; 500 ml/min; 1 hour; n = 10; the Noise + H2 group), or to H2 inhalation (n = 5; the H2 group). The acoustically evoked ABR threshold at 3.15, 6.30, 12.5, 20.0, and 30.0 kHz was assessed before and 4 days after impulse noise and/or H2 exposure. The cochleae were harvested after the final ABR assessment for quantification of hair cells. Noise exposure caused ABR threshold elevations at all frequencies (median 35, 35, 30, 35, and 35 dB SPL, the Noise group; 20, 25, 10, 13, and 20 dB SPL, the Noise + H2 group; P < .05) but significantly less so in the Noise + H2 group (P < .05). Outer hair cell (OHC) loss was in the apical, mid, and basal regions 8.8%, 53%, and 14% in the Noise group and 3.5%, 22%, and 1.2% in the Noise + H2 group. The corresponding inner hair cell (IHC) loss was 0.1%, 14%, and 3.5% in the Noise group and 0%, 2.8%, and 0% in the Noise + H2 group. The difference between the groups was significant in the basal region for OHCs (P = .003) and apical (P = .033) and basal (P = .048) regions for IHCs. Acute acoustic trauma can be reduced by H2 when inhaled immediately after impulse noise exposure.

Insomnia and related factors in patients with pre-existing psychiatric disorders compared to the general population during the COVID-19 lockdown: Findings from the multicentric COMET study

BackgroundThe COVID-19 pandemic has heavily impacted social, economic and health systems worldwide. Necessary confinement measures have, in turn, contributed to the occurrence of several stress-related conditions and deterioration of pre-existing mental conditions, including insomnia. ObjectiveThe present study sought to investigate the occurrence and severity of insomnia during the COVID-19 lockdown among psychiatric patients and in the general population in the largest Italian sample examined to date. Potential factors associated with a risk of developing insomnia in the global sample were examined as well. MethodsA sample of 20,720 people (5.5% of them being psychiatric patients) was assessed through an online survey conducted during lockdown between March and May 2020. To investigate the occurrence and severity of sleep related issues, the Insomnia Severity Index (ISI) was used. In order to evaluate factors associated with the severity of insomnia in the global sample, multivariate linear regression models were performed. ResultsDuring the lockdown, patients with pre-existing mental disorders reported a mean higher score on the ISI scale (p < 0.001) compared to the general population. According to the multivariate regression models, the first three weeks of lockdown were significantly associated with a higher risk of insomnia, but the risk disappeared in the fourth week. Other associated factors included: the presence of a pre-existing mental disorder, ages 24 to 64 years old, and/or being female (p < 0.001). ConclusionsAlthough containment measures represent essential public health strategies to avoid the spread of the COVID-19 pandemic, sleep was one of the aspects affected during the early stages of the lockdown in both people with pre-existing mental disorders and general population. As an integral part of COVID-19 intervention, it is useful to raise awareness about these issues and to adopt both preventive and therapeutic interventions.

N-trans-feruloyltyramine Protects Human Neuroblastoma SK-N-SH Cell Line Against H2O2-Induced Cytotoxicity

Excessive accumulation of reactive oxygen species (ROS) has been regarded as a major contributor of pathogenesis in neurodegenerative diseases. N- trans-feruloyltyramine (NTF), an alkaloid isolated from several plants, has demonstrated an ability to be a potent antioxidant. In this study, the antioxidative and anti-apoptotic properties of NTF extracted from the stems of Polyalthia suberosa were investigated in the human neuroblastoma cell line SK-N-SH. NTF at concentrations ranging from 10 µM to 500 µM were not toxic to cells and reduced intracellular ROS levels significantly. Furthermore, pre-treatment of NTF significantly decreased H2O2-induced ROS generation and attenuated H2O2-mediated cytotoxicity. An increase in the expression of Bax and activated caspase-3 and reduction of Bcl-2 mediated by H2O2 was reversed by pre-treating the cells with 100 µM NTF. Likewise, NTF suppressed the increase of caspase-3 activity induced by H2O2. In conclusion, the findings reveal that NTF improves H2O2-induced intracellular ROS generation and decreases apoptosis. These protective effects of NTF could be useful for oxidative stress-related neurodegenerative conditions.

Enhancing Endocannabinoid Signaling via β-Catenin in the Nucleus Accumbens Attenuates PTSD- and Depression-like Behavior of Male Rats.

Inhibition of fatty acid amide hydrolase (FAAH), which increases anandamide levels, has been suggested as a potential treatment for stress-related conditions. We examined whether the stress-preventing effects of the FAAH inhibitor URB597 on behavior are mediated via β-catenin in the nucleus accumbens (NAc). Male rats were exposed to the shock and reminders model of PTSD and then treated with URB597 (0.4 mg/kg; i.p.). They were tested for anxiety- (freezing, startle response), depression-like behaviors (despair, social preference, anhedonia), and memory function (T-maze, social recognition). We also tested the involvement of the CB1 receptor (CB1r), β-catenin, and metabotropic glutamate receptor subtype 5 (mGluR5) proteins. URB597 prevented the shock- and reminders-induced increase in anxiety- and depressive-like behaviors, as well as the impaired memory via the CB1r-dependent mechanism. In the NAc, viral-mediated β-catenin overexpression restored the behavior of rats exposed to stress and normalized the alterations in protein levels in the NAc and the prefrontal cortex. Importantly, when NAc β-catenin levels were downregulated by viral-mediated gene transfer, the therapeutic-like effects of URB597 were blocked. We suggest a potentially novel mechanism for the therapeutic-like effects of FAAH inhibition that is dependent on β-catenin activation in the NAc in a PTSD rat model.

Toward an Understanding of the Russian-Ukrainian War Impact on University Students and Personnel

Background On February 24, 2022, Russia invaded Ukraine provoking the most serious military conflict in Central Europe since 1945. By mid-May 2022, thousands of Ukrainian civilians have been killed or injured and millions relocated in the country or dispersed to other, mostly European, countries. To our knowledge, this is the first study on the impact of the war on the mental and emotional well-being of Ukrainian civilians—university students and personnel. Methods A snowball, non-probability sampling technique, was used for online survey data collection among students and personnel of 4 universities from May 5 to May 17, 2022. Four reliable instruments were used to collect information on the fear of war, resilience, burnout, and loneliness. Additional information was collected on substance use and eating behavior. Results Most respondents (97.8%) reported deterioration of their psycho-emotional status including depression (84.3%), exhaustion (86.7%), loneliness (51.8%), nervousness (84.4%), and anger (76.9%)—students more than personnel, females more than males. The use of substances (i.e., tobacco, alcohol, pain relievers, and sedatives) has increased as well as loneliness associated with fear, burnout and lower resilience. However, despite these conditions, 12.7% of the respondents have reported the war has not affected them. Conclusion Study findings are preliminary and limited in terms of time and location of data collection. However, results confirm the negative effects of war associated with mental health, fear, substance use, stress, loneliness, burnout, and other related conditions. Further research is needed to confirm the findings including the long-term impact of the war on the health and well-being of Ukrainian citizens.

C86 TAKO–TSUBO SYNDROME IN PATIENTS WITH COVID–19: A SINGLE CENTRE RETROSPECTIVE CASE SERIES

BackgroundCOVID–19 presents with a wide range of symptoms, from mild flu–like complaints to severe acute respiratory distress and cardiovascular complications. Recent literature provides some case reports of Tako–Tsubo syndrome (TTS) in COVID–19 patients. However, its prevalence, pathophysiological mechanisms and prognostic impact in this setting is unknown.MethodsWe collected data of patients hospitalized for COVID–19 in our multidisciplinary COVID–19 department who had a diagnosis of TTS during hospitalization. The criteria for hospital admission were: 1) naso–pharyngeal polymerase chain reaction diagnosis of SARS–CoV–2 infection and 2) symptoms and signs of mild–moderate COVID–19 with a paO2/FIO2 ratio > 200. The period of the study covered the second and third wave of the pandemic in Italy.ResultsOf 635 patients admitted to our centre, we had four cases, two males and two females, with TTS associated with COVID–19. No patient had any classical trigger for TTS except for COVID–19. Mean age was 72 years (67–81) and all patients had a diagnosis of SARS–CoV–2–related interstitial pneumonia confirmed by computed tomography. One patient was admitted to our centre after stabilization of a critical respiratory distress syndrome that required intubation. All patients showed typical apical ballooning with a transitory reduction of left ventricle (LV) systolic function. The mean LV ejection fraction (LVEF) at TTS onset was 42% (40–48%). ECG showed ST–segment elevation in two cases, while an evolution with negative T waves and long QTc was observed in all patients. All patients were treated in the intensive care unit (ICU), with a median ICU stay of 9 days. The long ICU stay duration was due to intercurrent superinfections. All patients recovered a normal LVEF before discharge. The mean value of the high–sensitivity troponin T peak was 1092 ng/L. Three patients underwent coronary angiography. One patient needed vasopressors in the acute phase. Two patients had a previous diagnosis of cognitive impairment. The time interval from hospital admission to TTS onset was 4 (2–6) days, and the time interval from COVID–19 symptom onset to TTS diagnosis was 10 (8–12) days. The mean hospital stay was 32 days (26–37).ConclusionCOVID–19 may be a trigger for TTS. Possible mechanisms to explain the contribution of COVID–19 to TTS development include the activation of the inflammatory cascade, direct myocardial injury, and stress–related conditions due to COVID–19.

Platinum Nanoparticles: The Potential Antioxidant in the Human Lung Cancer Cells.

Oxidative stress-related conditions associated with lung cells, specifically lung cancer, often lead to a poor prognosis. We hypothesized that platinum nanoparticles (PtNPs) can play a role in reversing oxidative stress in human lung adenocarcinoma A549 epithelial lung cell lines. Hydrogen peroxide (H2O2) was used to induce oxidative stress in cells, and the ability of PtNPs to lower the oxidative stress in the H2O2 treated epithelial lung cell line was determined. The differential capacity of PtNPs to remove H2O2 was studied through cell viability, nanoparticle uptake, DNA damage, ROS production, and antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and catalase). Results indicated that a higher concentration of PtNPs exhibited a higher antioxidant capacity and was able to reduce DNA damage and quench ROS production in the presence of 350 µM H2O2. All antioxidant enzymes’ activities also increased in the PtNPs treatment. Our data suggested that PtNPs could be a promising antioxidant in the treatment of lung cancer.

The Anterior Piriform Cortex and Predator Odor Responses: Modulation by Inhibitory Circuits.

Rodents acquire more information from the sense of smell than humans because they have a nearly fourfold greater variety of olfactory receptors. They use olfactory information not only for obtaining food, but also for detecting environmental dangers. Predator-derived odor compounds provoke instinctive fear and stress reactions in animals. Inbred lines of experimental animals react in an innate stereotypical manner to predators even without prior exposure. Predator odors have also been used in models of various neuropsychiatric disorders, including post-traumatic stress disorder following a life-threatening event. Although several brain regions have been reported to be involved in predator odor-induced stress responses, in this mini review, we focus on the functional role of inhibitory neural circuits, especially in the anterior piriform cortex (APC). We also discuss the changes in these neural circuits following innate reactions to odor exposure. Furthermore, based on the three types of modulation of the stress response observed by our group using the synthetic fox odorant 2,5-dihydro-2,4,5-trimethylthiazoline, we describe how the APC interacts with other brain regions to regulate the stress response. Finally, we discuss the potential therapeutic application of odors in the treatment of stress-related disorders. A clearer understanding of the odor–stress response is needed to allow targeted modulation of the monoaminergic system and of the intracerebral inhibitory networks. It would be improved the quality of life of those who have stress-related conditions.

Chronic Stress-Related Gastroenteric Pathology in Cheetah: Relation between Intrinsic and Extrinsic Factors.

Simple SummaryThe cheetah is the fastest land mammal. Habitat destruction, high mortality due to other predators, and illegal wildlife trade has led to a decrease in the wild population. Currently, the global adult population present in their natural habitat is estimated to be 7100 individuals. In captivity, the population suffers from limited reproduction and disease. Both the wild and captive populations have reduced genetic diversity from a historic bottleneck, leading to increased ecological and environmental vulnerability. Over the years, conservation programs have been developed for habitat protection, management of human–animal conflict, and the study of disease and genetics. Among these, the one with the greatest prevalence in captivity is chronic gastritis. This review analyzes the scientific literature on gastric pathology in cheetah, with the potential causes divided into “extrinsic factors”, such as living conditions and diet, and “intrinsic factors”, including the presence of Helicobacter-like organisms and the genetic predisposition.The rapid decline of cheetah (Acinonyx jubatus) throughout their range and long-term studies of captive breeding has increased conservation action for this species including the study of chronic diseases. Gastritis is one of the captive diseases that leads to high mortality presented with symptoms including vomiting, diarrhea, anorexia, and weight loss. The disease presents different histological lesions in the gastrointestinal tract that are characterized by inconstant and different clinical appearance in captive and free-range cheetahs. The aim of this review is to summarize the causes of chronic gastritis in the cheetah. Factors including diet, living conditions, infections with gastric Helicobacter-like organisms (GHLOs), the lack of genetic polymorphism and the cheetah’s specific-immunocompetence are analyzed. All studies on gastroenteric cheetah pathologies, conducted between 1991 (to the best of our knowledge, the first report on online databases) and 2021, are included in this review, highlighting the possible correlation between stress-related captive conditions and chronic gastric pathology.

Perceived Stress, Cortical GABA, and Functional Connectivity Correlates: A Hypothesis-Generating Preliminary Study.

Stress exposures and dysregulated responses to stress are implicated in psychiatric disorders of mood, anxiety, and cognition. Perceived stress, an individual's appraisal of experienced stress and ability for coping, relates to dysregulated functioning in resting state brain networks. Alterations in GABAergic function may underlie perceived stress-related functional dysregulation in resting state networks but this has not yet been explored. Therefore, the current study examined the association of perceived stress, via the Perceived Stress Scale (PSS), with prefrontal GABA levels and corresponding resting state functional connectivity (RSFC) alterations. Twelve women and five men, ages 35–61, participated. MR spectroscopy was used to measure brain GABA levels in the anterior cingulate cortex (ACC), left dorsolateral prefrontal cortex (DLPFC), and ventromedial prefrontal cortex (VMPFC). Resting state functional scans acquired at 3 Tesla were used to measure RSFC within and between the default mode (DMN), salience (SN), and central executive networks (CEN), hippocampus and amygdala. We observed significant negative correlations between total PSS scores and left DLPFC GABA levels (r = −0.62, p = 0.023). However, PSS scores were not significantly correlated with RSFC measures (all p > 0.148). These preliminary results support a relationship between perceived stress and GABAergic functioning in DLPFC, a core node of the CEN, an intrinsic network thought to underlie goal-directed attentional processes. Our findings extend previous work suggesting that functioning in the CEN is related to perceived stress and may inform treatment strategies to improve outcomes in stress-related conditions.

Effects of an integrated mindfulness intervention for veterans with diabetes distress: a randomized controlled trial.

IntroductionUS military veterans have disproportionately high rates of diabetes and diabetes-related morbidity in addition to being at risk of comorbid stress-related conditions. This study aimed to examine the effects of a technology-supported mindfulness intervention integrated into usual diabetes care and education on psychological and biobehavioral outcomes.Research design and methodsVeterans (N=132) with type 1 or 2 diabetes participated in this two-arm randomized controlled efficacy trial. The intervention arm received a one-session mindfulness intervention integrated into a pre-existing program of diabetes self-management education and support (DSMES) plus one booster session and 24 weeks of home practice supported by a mobile application. The control arm received one 3-hour comprehensive DSMES group session. The primary outcome was change in diabetes distress (DD). The secondary outcomes were diabetes self-care behaviors, diabetes self-efficacy, post-traumatic stress disorder (PTSD), depression, mindfulness, hemoglobin A1C (HbA1C), body weight, and blood pressure. Assessments were conducted at baseline, 12 weeks, and 24 weeks. Participant satisfaction and engagement in home practice were assessed in the intervention group at 12 and 24 weeks.ResultsIntention-to-treat group by time analyses showed a statistically significant improvement in DD in both arms without significant intervention effect from baseline to 24 weeks. Examination of distal effects on DD between weeks 12 and 24 showed significantly greater improvement in the intervention arm. Improvement in DD was greater when baseline HbA1C was <8.5%. A significant intervention effect was also shown for general dietary behaviors. The secondary outcomes diabetes self-efficacy, PTSD, depression, and HbA1C significantly improved in both arms without significant intervention effects. Mindfulness and body weight were unchanged in either group.ConclusionsA technology-supported mindfulness intervention integrated with DSMES showed stronger distal effects on DD compared with DSMES control. Examination of longer-term outcomes, underlying mechanisms, and the feasibility of virtual delivery is warranted.Trial registration numberNCT02928952.

Sensory Processing, Perceived Stress and Burnout Symptoms in a Working Population during the COVID-19 Crisis

Although previous research suggests an association between sensory processing and perceived stress in a broad spectrum of mental health conditions, it remains unclear whether this phenomenon occurs independently from psychopathology. The present study investigated the association between sensory processing patterns, perceived stress and occupational burnout as a stress-related condition in a working population. We focused on different aspects of sensory processing and used the momentum of a particularly stressful period: during the first months of the global COVID-19 crisis. A total of 116 workers at a mental healthcare institution in The Netherlands completed the Adolescent/Adult Sensory Profile (AASP), the Perceived Stress Scale (PSS-10) and the Burnout Assessment Tool (BAT). Our results demonstrated that higher scores on sensory sensitivity and low registration were associated with higher scores on perceived stress and core burnout symptoms. Sensory hypersensitivity was also associated with more secondary burnout symptoms. Associations were not driven by underlying sensory-related disorders (e.g., ASD or ADHD). In conclusion, sensory processing difficulties are relevant predictors of stress and occupational burnout, also in healthy employees. This phenomenon warrants further attention, as relatively simple adjustments in working environment may possess important preventive effects.

Defining a new perspective in Environmental Health: the healing environment.

With pollution-related health problems on the rise, the focus of modern Environmental Health (EH) has mostly been placed on toxicology and exposure science. Despite the importance of toxicological aspects, the environment should be studied not only to identify pollution-related hazards, but also to investigate potentially therapeutic and health-enhancing effects of its elements. Generally speaking, it is possible to benefit from a natural environment with a full-immersion experience or with a single-element interaction. Recently, scientific evidence is accumulating on the beneficial effects of natural settings for well-being promotion and psycho-physical health, especially for stress reduction and prevention of stress-related conditions. In light of these considerations, the paradigm of EH can change: the environment we live in should be considered not only as a precious resource to be protected against pollution (thus preventing the consequent health hazards), but, in a proactive vision, also as a potential source of elements capable of actively maintaining and promoting health and well-being.

Meditation and Aerobic Exercise Enhance Mental Health Outcomes and Pattern Separation Learning Without Changing Heart Rate Variability in Women with HIV.

Mental and physical (MAP) training targets the brain and the body through a combination of focused-attention meditation and aerobic exercise. The following feasibility pilot study tested whether 6 weeks of MAP training improves mental health outcomes, while enhancing discrimination learning and heart rate variability (HRV) in a group of women living with human immunodeficiency virus (HIV) and other stress-related conditions. Participants were assigned to training (n = 18) or no-training control (n = 8) groups depending on their ability and willingness to participate, and if their schedule allowed. Training sessions were held once a week for 6 weeks with 30 min of meditation followed by 30 min of aerobic exercise. Before and after 6 weeks of training, participants completed the Behavioral Pattern Separation Task as a measure of discrimination learning, self-report questionnaires of ruminative and trauma-related thoughts, depression, anxiety, and perceived stress, and an assessment of HRV at rest. After training, participants reported fewer ruminative and trauma-related thoughts, fewer depressive and anxiety symptoms, and less perceived stress (p’s < 0.05). The positive impact on ruminative thoughts and depressive symptoms persisted 6 months after training. They also demonstrated enhanced discrimination of similar patterns of information (p < 0.05). HRV did not change after training (p > 0.05). Combining mental and physical training is an effective program for enhancing mental health and aspects of cognition in women living with HIV, although not necessarily through variance in heart rate.

Secondary Traumatisation and Emotional Exhaustion in Mental Healthcare Providers: The Mediating Role of Social Support

Background: Burnout, especially emotional exhaustion, is common among mental healthcare providers (MHP). It is caused by exposure to prolonged stress related job conditions, such as secondary traumatisation. Social support is a protective factor for developing emotional exhaustion. In addition, higher levels of social support are associated with lower levels of secondary traumatisation. However, it is unclear how social support and secondary traumatisation are related. Social support may be a protective factor for developing secondary traumatisation, as it is for emotional exhaustion. On the other hand, MHP who suffer more from secondary traumatisation might experience less social support, for example because they fear stigmatisation. This study examined whether social support mediates the relationship between secondary traumatisation and emotional exhaustion. Further, it is explored whether the relation between secondary traumatisation and social support is moderated by profession (physicians, psychologists and case managers). Method: In total, 593 MHP participated in this cross-sectional study. Participants completed a questionnaire including demographic characteristics, secondary traumatisation, emotional exhaustion, and social support. Results: It was shown that no MHP experience high levels of secondary traumatisation and relatively few experience high levels of emotional exhaustion, while they do experience much social support. Furthermore, as hypothesized, it was found that the relationship between secondary traumatisation and emotional exhaustion is partially mediated by social support. Finally, no moderation effect of profession was found. Conclusion: These results imply that MHP have access to social support and make use of it, preventing emotional exhaustion. Mental healthcare organisations should maintain these resources for social support to prevent emotional exhaustion. MHP who are less inclined to seek social support should receive extra attention, as should MHP who are more at risk of secondary traumatisation. Even though MHP experience the availability of social support, still 25% of the MHP do experience emotional exhaustion. Future research should examine which factors for this group contribute to the development of emotional exhaustion so that appropriate measures can be taken.

How Epigenetics Can Enhance Pig Welfare?

Simple SummaryIn the pig industry, new market trends and consumer demands have emerged over the past decades, which includes increased concerns about how animals are raised on farms. As a consequence of consumers’ concerns, technologies capable of predicting animal welfare on farms have been explored. One of the technologies that are permeating the frontier of knowledge in this area are epigenetic biomarkers. Epigenetic biomarkers are biochemical markers surrounding the genome, which may be able to predict the exposures that individuals had during their lifetime. These markers represent an advance in the molecular level accuracy to support the current welfare indicators. In this literature review focused on pigs, we show some studies already carried out, we performed an integrative analysis of the already reported genes surrounding epi-biomarkers, and we highlight the benefits of investing efforts in this research field to enhance animal welfare and consumers’ trust.Epigenetics works as an interface between the individual and its environment to provide phenotypic plasticity to increase individual adaptation capabilities. Recently, a wide variety of epi-genetic findings have indicated evidence for its application in the development of putative epi-biomarkers of stress in farm animals. The purpose of this study was to evaluate previously reported stress epi-biomarkers in swine and encourage researchers to investigate potential paths for the development of a robust molecular tool for animal welfare certification. In this literature review, we report on the scientific concerns in the swine production chain, the management carried out on the farms, and the potential implications of these practices for the animals’ welfare and their epigenome. To assess reported epi-biomarkers, we identified, from previous studies, potentially stress-related genes surrounding epi-biomarkers. With those genes, we carried out a functional enrichment analysis of differentially methylated regions (DMRs) of the DNA of swine subjected to different stress-related conditions (e.g., heat stress, intrauterine insult, and sanitary challenges). We identified potential epi-biomarkers for target analysis, which could be added to the current guidelines and certification schemes to guarantee and certify animal welfare on farms. We believe that this technology may have the power to increase consumers’ trust in animal welfare.

CRF-R1 Antagonist Treatment Exacerbates Circadian Corticosterone Secretion under Chronic Stress, but Preserves HPA Feedback Sensitivity.

Despite promising initial reports, corticotropin-releasing factor receptor type-1 (CRF-R1) antagonists have mostly failed to display efficacy in clinical trials for anxiety or depression. Rather than broad-spectrum antidepressant/anxiolytic-like drugs, they may represent an ‘antistress’ solution for single stressful situations or for patients with chronic stress conditions. However, the impact of prolonged CRF-R1 antagonist treatments on the hypothalamic–pituitary–adrenal (HPA) axis under chronic stress conditions remained to be characterized. Hence, our study investigated whether a chronic CRF-R1 antagonist (crinecerfont, formerly known as SSR125543, 20 mg·kg−1·day−1 ip, 5 weeks) would alter HPA axis basal circadian activity and negative feedback sensitivity in mice exposed to either control or chronic stress conditions (unpredictable chronic mild stress, UCMS, 7 weeks), through measures of fecal corticosterone metabolites, plasma corticosterone, and dexamethasone suppression test. Despite preserving HPA axis parameters in control non-stressed mice, the 5-week crinercerfont treatment improved the negative feedback sensitivity in chronically stressed mice, but paradoxically exacerbated their basal corticosterone secretion nearly all along the circadian cycle. The capacity of chronic CRF-R1 antagonists to improve the HPA negative feedback in UCMS argues in favor of a potential therapeutic benefit against stress-related conditions. However, the treatment-related overactivation of HPA circadian activity in UCMS raise questions about possible physiological outcomes with long-standing treatments under ongoing chronic stress.

Chronic Stress and Gonadectomy Affect the Expression of Cx37, Cx40 and Cx43 in the Spinal Cord.

The study aimed to determine whether the exposure to chronic stress and/or performance of gonadectomy might lead to disturbance in the expression of connexin (Cx) 37, 40 and 43 in the spinal cord (SC), as a potential explanation for sex differences in stress-related chronic pain conditions. After the rats were sham-operated or gonadectomized, three 10-day sessions of sham or chronic stress were applied. Immunohistochemistry and transmission electron microscopy (TEM) were used to examine Cx localization and expression in the SC. The gonadectomy resulted in an increase of Cx37 expression in the dorsal horn (DH) of the female rats, but chronic stress suppressed the effects of castration. In male rats, only the combined effects of castration and chronic stress increased Cx37 expression. The influence of chronic stress on the DH Cx40 expression was inversely evident after the castration: increased in the ovariectomized female rats, while decreased in the orchidectomized male rats. We did not find any effect of chronic stress and castration, alone or together, on Cx43 expression in the DH, but the percentage of Cx43 overlapping the astrocyte marker glial fibrillary acidic protein (gfap) increased in the male stressed group after the castration. In conclusion, the association of the chronic stress with sex hormone depletion results in disturbances of the SC Cx expression and might be a possible mechanism of disturbed pain perception after chronic stress exposure.

Application areas and effects of aquatic therapy WATSU – A survey among practitioners

IntroductionWATSU (WaterShiatsu) is a treatment administered in warm water. The present study investigated if and how frequently scientifically studied application areas and effects of WATSU occur in practice, whether similar effectiveness of WATSU is observed in trials and practice, and whether practitioners can contribute additional application areas and effects of WATSU. MethodsApplication areas and effects of WATSU reported in a recent systematic review were extracted verbatim to be assessed in a worldwide multilingual cross section online survey, generating quantitative and qualitative data. A pre-test and retest were conducted to ensure quality and evaluate the questionnaire's psychometric properties. ResultsAnswers of 191 respondents were processed. All proposed 26 application areas and 20 effects were confirmed, each with relatively high ratings of observed effectiveness of WATSU. WATSU was frequently applied in healthy individuals (including during pregnancy), and individuals in various pain- (e.g., low back pain, neck pain, myofascial pain, fibromyalgia) and stress-related (e.g., stress, depression, sleep disorders, fatigue, anxiety disorders) conditions. Frequently confirmed effects were physical relaxation, relief of physical tension, pain relief, increased mobility and flexibility, improved quality of life, spiritual experiences, and increased psychological health. Respondents contributed 73 additional application areas and effects (both, mental and physical) of WATSU. ConclusionsApplication areas and effects of WATSU are consistently employed practically and scientifically. Respondents’ ratings of effectiveness of WATSU match tentative research efforts. WATSU is cautiously recommended for the use in pain- and stress-related conditions. Short- and long-term effectiveness of WATSU need to be evaluated in high level intervention studies.

Phytochemical Composition, Anti-Inflammatory and ER Stress-Reducing Potential of Sambucus ebulus L. Fruit Extract.

Sambucus ebulus L. (SE) fruits are used for their immunostimulation, hematopoietic and antiviral potential. Recently, we focused on analyzing the mechanism underlying SE fruit aqueous extract’s (FAE) immunomodulation and anti-inflammatory activities, with attention to its endoplasmic reticulum (ER) stress-reducing potential. J774A.1 macrophages were treated with SE FAE alone or in conditions of lipopolysaccharides (LPS) stimulation. Using GC–MS and LC–MS/MS, its phytochemical composition was analyzed. To measure transcription and protein levels, we used qPCR and Western blot, respectively. The prevailing phytochemicals in SE FAE were hydroxycinnamic acids, proanthocyanidins and anthocyanins. The content of some amino acids, organic acids, alcohols, fatty acids and esters were newly reported. Extracts exerted an immunostimulation potential by stimulating IL-6, TNFα, Ccl2, COX2 and iNOS transcription, without inducing ER stress. SE FAE suppressed the LPS-induced transcription of inflammation related genes (IL-1β, IL-6, TNFα, Ccl2, Icam-1, Fabp4, COX2, iNOS, Noxo1, IL-1ra, Sirt-1) and reduced the protein levels of iNOS, peIF2α, ATF6α and CHOP. The effects were comparable to that of salicylic acid. SE suppresses LPS-stimulated inflammatory markers on the transcription and translation levels. Targeting ER stress is possibly another mechanism underlying its anti-inflammatory potential. These findings reveal the potential of SE fruits as a beneficial therapeutic of inflammation and ER stress-related pathological conditions.