Cardiovascular diseases are the leading cause of death worldwide. Pathophysiologically, metabolic and inflammatory processes contribute substantially to the development and progression of cardiovascular diseases. Over the past decade, the role of disease-propagating inflammatory processes has been strengthened and reframed, leading to trials testing anti-inflammatory drugs for the treatment of atherosclerosis and its complications. Despite these achievements, further research in both pre-clinical and clinical studies is warranted to explore new targets, to better identify responders, and to refine therapy strategies to combat inflammation in human disease. Environmental disturbances, so-called lifestyle-associated cardiovascular risk factors, greatly alter the immune system in general and leukocytes in particular, thus affecting the progression of atherosclerosis. Epidemiological studies have shown that exposure to mental stress can be closely linked to the occurrence of cardiovascular disease. Here, we describe how acute and chronic mental stress alter the immune system via neuroimmune interactions, thereby modifying vascular inflammation. In addition, we identify gaps that still need to be addressed in the future.
UNASSIGNED: Herz-Kreislauf-Erkrankungen sind weltweit die häufigste Todesursache. Pathophysiologisch tragen metabolische und inflammatorische Prozesse wesentlich zur Entstehung und zum Fortschreiten von Herz-Kreislauf-Erkrankungen bei. In den vergangenen Jahren wurde die Beteiligung inflammatorischer Prozesse hieran immer deutlicher, was zu einer Reihe von randomisierten kontrollierten Studien mit antiinflammatorischen Medikamenten zur Behandlung von Atherosklerose geführt hat. Diese ersten Erfolge unterstreichen die Notwendigkeit präklinischer Studien zur Identifikation neuer therapeutischer Ansatzpunkte in der Behandlung der Atherosklerose. Es gibt eine Vielzahl lebensstilassoziierter kardiovaskulärer Risikofaktoren, die das Immunsystem beeinflussen. Epidemiologische Studien ergaben, dass sowohl akuter als auch chronischer Stress eng mit dem Auftreten von Herz-Kreislauf-Erkrankungen in Verbindung gebracht werden können. In der vorliegenden Arbeit wird beschrieben, wie akuter und chronischer Stress das Immunsystem durch Interaktion mit dem Nervensystem verändert und dadurch die vaskuläre Inflammation verstärkt. Darüber hinaus werden Lücken im bisherigen Verständnis der Pathogenese der Atherosklerose aufgezeigt, die es in Zukunft zu schließen gilt.

Stressful life event is closely associated with depression, thus strategies that blunt or prevent the negative effect stress on the brain might benefits for the treatment of depression. Although previous study showed the role of protein kinase R (PKR)-like ER kinase (PERK) in inflammation related depression, its involvement in the neuropathology of chronic stress induced depression is still unknown. We tried to explore whether block the PERK pathway would alleviate the animals\' depression-like behavior induced by chronic restraint stress (CRS) and investigate the underlying mechanism. The CRS-exposed mice exhibited depression-like behavior, including anhedonia in the sucrose preference test (SPT), and increased immobility time in tail suspension test (TST) and forced swim test (FST). ISRIB administration for 2 weeks significantly improved the depression-like behavior in male mice exposed to CRS, which was manifested by markedly increasing the sucrose preference and reducing the immobility time in the FST and TST. However, we observed that exposure to the same dose of ISRIB in CRS female mice only showed improved anhedonia-like deficits,leaving unaltered improvement in the FST and TST. Mechanically, we found that ISRIB reversed the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, indicating decreased levels of serum corticosterone, reduced hippocampal glucocorticoidreceptor (GR) expression and expression of FosB in hypothalamic paraventricularnucleus (PVN), which was accompanied by preserved hippocampal neurogenesis. The present findings further expand the potential role of ER stress in depression and provide important details for a therapeutic path forward for PERK inhibitors in mood disorders.

Chronic stress negatively affects the immune system and promotes tumor progression. Tumor-associated macrophage (TAM) is an important component of the tumor immune microenvironment. However, the influence of chronic stress on M1-M2 polarization of TAM is unclear. We used flow cytometry to measure the M1-M2 polarization of TAM in chronic stress hepatocellular carcinoma (HCC) bearing mice. We also measured the level of norepinephrine and blocked β-adrenergic signaling to explore the role of β-adrenergic receptor in the effect of chronic stress on M1-M2 polarization of TAM. We found that chronic stress disrupts the M1-M2 polarization in tumor tissues, increased the level of CD11b+Ly6C+CCR2+ monocyte and interleukin-1beta in blood and promoted the growth of HCC. Furthermore, chronic stress upregulated the level of CCL2 in tumor tissues. Finally, we found chronic stress increased norepinephrine level in serum and propranolol, a blocker of β-adrenergic signaling, inhibited HCC growth, recovered the M1-M2 polarization balance of TAM in tumor tissues, blocked the increase of CD11b+Ly6C+CCR2+ monocytes in blood, and blocked the increase of CCL2 in tumor tissues induced by chronic stress. Our study indicated that chronic stress disrupts the M1-M2 polarization balance of TAMs through β-adrenergic signaling, thereby promoting the growth of HCC.

Misophonia is a neurophysiological disorder with behavioral implications, is complex and multifactorial in origin, and is characterized by an atypical and disproportionate emotional response to specific sounds or associated visual stimuli. Triggers include human-generated sounds, mainly sounds related to feeding and breathing processes, and repetitive mechanical sounds. In response to the triggering stimulus, the patient experiences immediate, high-intensity, disproportionate physical and emotional reactions that affect their quality of life and social functioning. The symptoms of misophonia can occur at any age, but onset in childhood or adolescence is most common. Affected children live in a constant state of anxiety, suffer continuous physical and emotional discomfort, and are thus exposed to significant chronic stress. Chronic stress, especially during childhood, has consequences on the main biological systems through the dysregulation of the hypothalamic-pituitary-adrenal axis, including the gastrointestinal tract. Here, we provide arguments for a positive correlation between misophonic pathology and gastrointestinal symptoms, and this hypothesis may be the starting point for further longitudinal studies that could investigate the correlations between these childhood vulnerabilities caused by misophonia and their effect on the gastrointestinal system. Further research to study this hypothesis is essential to ensure correct and timely diagnosis and optimal psychological and pharmacological support.

Astrocyte dysfunctions have been consistently observed in patients affected with depression and other psychiatric illnesses. Although over the years our understanding of these changes, their origin, and their consequences on behavior and neuronal function has deepened, many aspects of the role of astroglial dysfunction in major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) remain unknown. In this review, we summarize the known astroglial dysfunctions associated with MDD and PTSD, highlight the impact of chronic stress on specific astroglial functions, and how astroglial dysfunctions are implicated in the expression of depressive- and anxiety-like behaviors, focusing on behavioral consequences of astroglial manipulation on emotion-related and fear-learning behaviors. We also offer a glance at potential astroglial functions that can be targeted for potential antidepressant treatment.

Stagnation in the development of novel therapeutic strategies for treatment-resistant depression has encouraged continued interest in improving preclinical methods. One tactic prioritizes the reverse translation of behavioral tasks developed to objectively quantify depressive phenotypes in patient populations for their use in laboratory animals via touchscreen technology. After cross-species concordance in task outcomes under healthy conditions is confirmed, construct validity can be further enhanced by identifying environmental stressors that reliably produce deficits in task performance that resemble those in depressive participants. The present studies characterized in male rats the ability of two chronic ecologically relevant stressors, inescapable ice water or isolated restraint, to produce depressive-like behavioral phenotypes in the Probabilistic Reward Task (PRT) and Psychomotor Vigilance Task (PVT). These tasks previously have been reverse-translated using touchscreen technology for rodents and nonhuman primates to objectively quantify, respectively, reward responsivity (anhedonia) and attentional processes (impaired cognitive function), each of which are core features of major depressive disorder. In the PRT, both inescapable ice water and isolated restraint produced persistent anhedonic phenotypes compared to non-stressed control performance (i.e., significantly blunted response bias for the richly rewarded stimulus). In the PVT, both chronic stressors impaired attentional processing, revealed by increases in titrated reaction times; however, these deficits largely subsided by the end of the chronic condition. Taken together, these findings confirm the ability of reverse-translated touchscreen tasks to effectively generate behavioral phenotypes that exhibit expected deficits in performance outcomes following exposure to chronic ecologically relevant stress. In turn, this approach is well positioned to appraise the ability of candidate therapeutics to attenuate or reverse such behavioral deficits and, thereby, contribute to preclinical medications development for treatment-resistant depression.

UNASSIGNED: Lifestyle interventions can prevent type 2 diabetes (T2D) by successfully inducing behavioral changes (eg, avoiding physical inactivity and sedentariness, increasing physical activity and/or healthy eating) that reduce body weight and normalize metabolic levels (eg, HbA1c). For interventions to be successful, it is important to influence \"behavioral mechanisms\" such as self-efficacy, which motivate behavioral changes. Theory-based expectations of how self-efficacy, chronic stress, and mood changed over time were investigated through a group-based behavior change intervention (PREMIT). At 8 intervention sites, PREMIT was offered by trained primary care providers in 18 group-sessions over a period of 36 months, divided into 4 intervention phases. Adherence to the intervention protocol was assessed.
UNASSIGNED: Participants (n = 962) with overweight and prediabetes who had achieved ≥8% weight loss during a diet reduction period and completed the intervention were categorized into 3 groups: infrequent, frequent, or very frequent group sessions attendance. The interactions between participation in the group sessions and changes in self-efficacy, stress, and mood were multivariate tested. Intervention sites were regularly asked where and how they deviated from the intervention protocol.
UNASSIGNED: There was no increase in the participants\' self-efficacy in any group. However, the level of self-efficacy was maintained among those who attended the group sessions frequently, while it decreased in the other groups. For all participants, chronic stress and the frequency of attending group sessions were inversely related. Significant differences in mood were found for all groups. All intervention centers reported specific activities, additional to intervention protocol, to promote participation in the group sessions.
UNASSIGNED: The results suggest that the behavioral changes sought by trained primary care providers are related to attendance frequency and follow complex trajectories. The findings also suggest that group-based interventions in naturalistic primary care settings aimed at preventing T2D require formats and strategies that encourage participants to attend group sessions regularly.

UNASSIGNED: Chronic workplace stress and burnout are impediments to physicians\' professional fulfillment, healthcare organizations\' efficiency, and patient care quality/safety. General surgery residents are especially at risk due to the complexity of their training. We report the protocol of a metaanalysis of chronic stress and burnout among Accreditation Council for Graduate Medical Education (ACGME)-affiliated general surgery residents in the era after duty-hour reforms, plus downstream effects on their health and clinical performance.
UNASSIGNED: The proposed systematic review and metaanalysis (PROSPERO registration CRD42021277626) will synthesize/pool data from studies of chronic stress and burnout among general surgery residents at ACGME-affiliated programs. The timeframe under review is subdivided into three intervals: (a) after the 2003 duty-hour restrictions but before 2011 reforms, (b) after the 2011 reforms but before the coronavirus pandemic, and (c) the first 3 years after the pandemic\'s outbreak. Only studies reporting outcomes based on validated instruments will be included. Qualitative studies, commentaries/editorials, narrative reviews, and studies not published in English will be excluded. Multivariable analyses will adjust for sample characteristics and the methodological quality of included studies.
UNASSIGNED: The metaanalysis will yield evidence reflecting experiences of North American-based general surgery residents in the years after ACGME-mandated duty-hour restructuring.

BACKGROUND: Differential exposure to chronic stressors by race/ethnicity may help explain Black-White inequalities in rates of preterm birth. However, researchers have not investigated the cumulative, interactive, and population-specific nature of chronic stressor exposures and their possible nonlinear associations with preterm birth. Models capable of computing such high-dimensional associations that could differ by race/ethnicity are needed. We developed machine learning models of chronic stressors to both predict preterm birth more accurately and identify chronic stressors and other risk factors driving preterm birth risk among non-Hispanic Black and non-Hispanic White pregnant women.
METHODS: Multivariate Adaptive Regression Splines (MARS) models were developed for preterm birth prediction for non-Hispanic Black, non-Hispanic White, and combined study samples derived from the CDC\'s Pregnancy Risk Assessment Monitoring System data (2012-2017). For each sample population, MARS models were trained and tested using 5-fold cross-validation. For each population, the Area Under the ROC Curve (AUC) was used to evaluate model performance, and variable importance for preterm birth prediction was computed.
RESULTS: Among 81,892 non-Hispanic Black and 277,963 non-Hispanic White live births (weighted sample), the best-performing MARS models showed high accuracy (AUC: 0.754-0.765) and similar-or-better performance for race/ethnicity-specific models compared to the combined model. The number of prenatal care visits, premature rupture of membrane, and medical conditions were more important than other variables in predicting preterm birth across the populations. Chronic stressors (e.g., low maternal education and intimate partner violence) and their correlates predicted preterm birth only for non-Hispanic Black women.
CONCLUSIONS: Our study findings reinforce that such mid or upstream determinants of health as chronic stressors should be targeted to reduce excess preterm birth risk among non-Hispanic Black women and ultimately narrow the persistent Black-White gap in preterm birth in the U.S.

BACKGROUND: Chronic stress-induced neuroinflammation plays a pivotal role in the development and exacerbation of mental disorders, such as anxiety and depression. Dimethyl Fumarate (DMF), an effective therapeutic agent approved for the treatment of multiple sclerosis, has been widely reported to display anti-inflammatory and anti-oxidative effects. However, the impact of DMF on chronic stress-induced anxiety disorders and the exact underlying mechanisms remain largely unknown.
METHODS: We established a mouse model of chronic social defeat stress (CSDS). DMF was administered orally 1 h before daily stress session for 10 days in CSDS + DMF group. qRT-PCR and western blotting were used to analyze mRNA and protein expression of NLRP3, Caspase-1 and IL-1β. Immunofluorescence staining was carried out to detect the expression of Iba 1 and c-fos positive cells as well as morphological change of Iba 1+ microglia. Whole-cell patch-clamp recording was applied to evaluate synaptic transmission and intrinsic excitability of neurons.
RESULTS: DMF treatment significantly alleviated CSDS-induced anxiety-like behaviors in mice. Mechanistically, DMF treatment prevented CSDS-induced neuroinflammation by inhibiting the activation of microglia and NLRP3/Caspase-1/IL-1β signaling pathway in basolateral amygdala (BLA), a brain region important for emotional processing. Furthermore, DMF treatment effectively reversed the CSDS-caused disruption of excitatory and inhibitory synaptic transmission balance, as well as the increased intrinsic excitability of BLA neurons.
CONCLUSIONS: Our findings provide new evidence that DMF may exert anxiolytic effect by preventing CSDS-induced activation of NLRP3/Caspase-1/IL-1β signaling pathway and alleviating hyperactivity of BLA neurons.