Search Results (367)

Reactive molecules, including oxygen and nitrogen species, serve dual roles in human physiology. While they function as essential signaling molecules under normal physiological conditions, they contribute to cellular dysfunction and damage when produced in excess by normal metabolism or in response to stressors. Oxidative/nitrosative stress is a pathological state, resulting from the overproduction of reactive species exceeding the antioxidant capacity of the body, which is implicated in several chronic human diseases. Antioxidant therapies aimed at restoring redox balance and preventing oxidative/nitrosative stress have demonstrated efficacy in preclinical models. However, their clinical applications have met with inconsistent success owing to efficacy, safety, and bioavailability concerns. This summative review analyzes the role of reactive species in human pathophysiology, the mechanisms of action of antioxidant protection, and the challenges that hinder their translation into effective clinical therapies in order to evaluate potential emerging strategies such as targeted delivery systems, precision medicine, and synergistic therapeutic approaches, among others, to overcome current limitations. By integrating recent advances, this review highlights the value of targeting reactive species in the prevention and management of chronic diseases. Full article

Despite growing recognition of the role that social determinants of health (SDOHs) and health-related social needs (HRSNs) play in chronic disease, limited research has examined their associations with Chronic Obstructive Pulmonary Disease (COPD) in population-based studies. This cross-sectional study analyzed 2022 Behavioral Risk Factor Surveillance System (BRFSS) data from 37 U.S. states and territories to determine how financial hardship, food insecurity, employment loss, healthcare access barriers, and psychosocial stressors influence the prevalence of COPD. Weighted logistic regression models were used to assess the associations between COPD and specific SDOHs and HRSNs. Several individual SDOH and HRSN factors were significantly associated with COPD prevalence, with financial strain emerging as a particularly strong predictor. In models examining specific SDOH factors, economic hardships like inability to afford medical care were strongly linked to higher COPD odds. Psychosocial HRSN risks, such as experiencing mental stress, also showed moderate associations with increased COPD prevalence. These findings suggest that addressing both structural and individual-level social risks may be critical for reducing the prevalence of COPD in populations experiencing financial challenges. Full article

In rapidly urbanizing environments, environmental stressors—such as air pollution, noise, heat, and green space depletion—substantially exacerbate public health burdens, contributing to the global rise of non-communicable diseases, particularly hypertension, cardiovascular disorders, and mental health conditions. Despite expanding research on green spaces and health (+76.9%, 2019–2025) and optimization and algorithmic approaches (+63.7%), the compounded and synergistic impacts of these stressors remain inadequately explored or addressed within current urban planning frameworks. This study presents a Mixed Methods Systematic Review (MMSR) to investigate the potential of AI-driven urban design optimizations in mitigating these multi-scalar environmental health risks. Specifically, it explores the complex interactions between urbanization, traffic-related pollutants, green infrastructure, and architectural intelligence, identifying critical gaps in the integration of computational optimization with nature-based solutions (NBS). To empirically substantiate these theoretical insights, this study draws on longitudinal 24 h dynamic blood pressure (BP) monitoring (3–9 months), revealing that chronic exposure to environmental noise (mean 79.84 dB) increases cardiovascular risk by approximately 1.8-fold. BP data (average 132/76 mmHg), along with observed hypertensive spikes (systolic > 172 mmHg, diastolic ≤ 101 mmHg), underscore the inadequacy of current urban design strategies in mitigating health risks. Based on these findings, this paper advocates for the integration of AI-driven approaches to optimize urban environments, offering actionable recommendations for developing adaptive, human-centric, and health-responsive urban planning frameworks that enhance resilience and public health in the face of accelerating urbanization. Full article

Substance use is a critical public health issue in the U.S., with Black communities, particularly those with criminal justice contact, disproportionately affected. Chronic exposure to stressors can lead to substance use as a coping strategy. This study used data from 1476 Black adults with criminal justice involvement from the National Survey of American Life to examine how psychosocial stress and sleep disturbances relate to lifetime substance use and to determine if there are any sex differences. Sex-separate generalized linear models for a Poisson distribution with a log-link function estimated prevalence ratios and adjusted prevalence ratios (APRs) for lifetime alcohol abuse, lifetime cigarette, and marijuana use. Independent variables include stressors (family, person, neighborhood, financial, and work-related) and sleep problems, with covariates such as age, SES, and marital status. Lifetime alcohol abuse was associated with family stressors (APR = 2.72) and sleep problems (APR = 3.36) for males, and financial stressors (APR = 2.75) and sleep problems (APR = 2.24) for females. Cigarette use was linked to family stressors (APR = 1.73) for males and work stressors (APR = 1.78) for females. Marijuana use was associated with family stressors (APR = 2.31) and sleep problems (APR = 2.07) for males, and neighborhood stressors (APR = 1.72) for females. Lifetime alcohol abuse, as well as lifetime cigarette and marijuana use, was uniquely associated with various psychosocial stressors among Black adult males and females with criminal justice contact. These findings highlight the role of structural inequities in shaping substance use and support using a Social Determinants of Health framework to address addiction in this population. Full article

Background/Objectives: Environmental stressors, including spaceflight and altered gravity, can negatively affect the symbiotic relationship between the gut microbiome and host health. Dietary prebiotics, which alter components of the gut microbiome, show promise as an effective way to mitigate the negative impacts of stressor exposure. It remains unknown, however, if the stress-protective effects of consuming dietary prebiotics will extend to chronic altered-gravity exposure. Methods: Forty female C57BL/6 mice consumed either a control diet or a prebiotic diet containing galactooligosaccharides (GOS) and polydextrose (PDX) for 4 weeks, after which half of the mice were exposed to 3 times the gravitational force of Earth (3g) for an additional 4 weeks. Fecal microbiome samples were collected weekly for 8 weeks, sequenced, and analyzed using 16S rRNA gene sequencing. Terminal physiological endpoints, including immune and red blood cell characteristics, were collected at the end of the study. Results: The results demonstrate that dietary prebiotic consumption altered the gut microbial community structure through changes to β-diversity and multiple genera across time. In addition, consuming dietary prebiotics reduced the neutrophil-to-lymphocyte ratio (NLR) and increased red blood cell distribution width (RDW-CV). Importantly, the prebiotic diet prevented the impacts of altered-gravity on β-diversity and the bloom of problematic genera, such as Clostridium_sensu_stricto_1 and Turicibacter. Furthermore, several prebiotic diet-induced genera-level changes were significantly associated with several host physiological changes induced by 3g exposure. Conclusions: These data demonstrate that the stress-protective potential of consuming dietary prebiotics extends to environmental stressors such as altered gravity, and, potentially, spaceflight. Full article

Women’s greater vulnerability to intrusive memories following trauma may be partially explained by the influence of ovarian hormones on memory consolidation processes. Contributing to accumulating research examining the influence of ovarian hormones on the development of intrusive memories, we hypothesized that cyclical fluctuations in estradiol and progesterone, not merely absolute levels, contribute to this risk. We further hypothesized that hormonal contraceptives, which effectively eliminate fluctuations and keep ovarian hormones at chronic low levels, can convey protective effects against memory intrusions following analogue trauma exposure. We examined the development of memory intrusions following trauma film stressor exposure among men (n = 27), hormonal contraceptive (HC) users (n = 41), and naturally cycling (NC) women in the early follicular (EF; n = 24), late follicular (n = 20), ovulatory window (n = 14), and luteal phases (n = 21) for 5 days to assess whether low ovarian hormone levels convey a protective effect for women. Contrary to hypotheses, this study found no support for this prospect; rather, exposure to stressors during the window around ovulation increased the risk for more frequent intrusive memories. Enhanced stress responsivity may have particular effects on ovulation, promoting evolutionary fitness. Full article

Honey bees (Apis mellifera) are major pollinators, playing a critical role in global food production, biodiversity, and ecosystem stability. However, their populations are increasingly threatened by multiple interacting stressors, including pesticide exposure. Among these, agricultural insecticides and anti-Varroa acaricides such as dinotefuran and amitraz can persist in hive matrices, resulting in chronic and combined exposure. This study investigates the low lethal (LC₁₀ and LC₃₀) effects of these compounds, individually and in combination, on honey bee survival, immune function, oxidative stress responses, detoxification pathways, and hypopharyngeal gland morphology. Both pesticides negatively affected honey bee health at low lethal concentrations, with dinotefuran showing higher toxicity. Exposure led to the reduced survival, suppression of vitellogenin expression, and dysregulation of genes related to antioxidant defense, immunity, and detoxification. Additionally, high concentrations of dinotefuran and its combination with amitraz impaired hypopharyngeal gland morphology. Notably, co-exposure resulted in synergistic toxic effects, exacerbating physiological damage beyond individual treatments. These findings emphasize the potential risks of combined exposure to agricultural and beekeeping pesticides. A more comprehensive risk assessment and stricter regulations are urgently needed. Full article

Background/Objectives: Hypertension is a major contributor to cardiovascular diseases and is often intensified by psychological stress, which can also affect bone metabolism. Although both conditions independently compromise bone health, their combined impact—particularly under acute and chronic stress—remains unclear. This pilot study aimed to assess the effects of such stressors on bone structure in spontaneously hypertensive rats (SHRs). Methods: Forty male rats, both normotensive and SHRs, were randomly assigned to control, acute stress, or chronic stress groups. Acute stress involves a single 2 h physical restraint. Chronic stress was induced over 10 days using alternating stressors: agitation, forced swimming, physical restraint, cold exposure, and water deprivation. Tibial bones were analyzed by microcomputed tomography (micro-CT), and histology was performed using Hematoxylin and Eosin and Masson’s Trichrome stains. Results: Micro-CT showed increased trabecular bone volume in normotensive rats under chronic stress, whereas SHRs displayed impaired remodeling under both stress types. Histological analysis revealed preserved connective tissue overall but evident changes in growth plate structure among stressed rats. SHRs exhibited exacerbated trabecular formation and cartilage abnormalities, including necrotic zones. Conclusions: Both acute and chronic stress, especially in the context of hypertension, negatively affect bone remodeling and maturation. Despite the absence of overt inflammation, structural bone changes were evident, indicating potential long-term risks. These findings highlight the importance of further studies on stress–hypertension interactions in bone health as well as the exploration of therapeutic approaches to mitigate skeletal damage under such conditions. Full article

The race paradox in mental health refers to the phenomenon in which African Americans often demonstrate mental health outcomes that are comparable to or more favorable than those of non-Hispanic Whites, despite systemic socioeconomic disadvantage and disproportionate exposure to chronic stressors. Few studies have examined the mechanisms underlying this race paradox among older adults, and even fewer have explored the role of social participation. This study aims to examine whether social participation mediates the relationship between race and mental health. Longitudinal data were drawn from the National Social Life, Health, and Aging study Waves 1–3 (N = 1292). Race was dichotomized as African American and non-Hispanic White. Three types of social participation were assessed: volunteering, participating in organized groups, and attending religious services. Depressive symptoms were assessed as the mental health outcome. Path analyses were conducted to examine the aim. Results indicate that being African Americans predicted increased levels of religious attendance, which in turn, decreased the levels of depressive symptoms. Religious attendance is an underlying mechanism partially explaining the race paradox in mental health, and a modifiable factor that mitigates depressive symptoms. Culturally sensitive interventions promoting social participation are warranted. Full article

The modern workplace grapples with a human energy crisis, characterized by chronic exhaustion, disengagement, and emotional depletion among employees. Traditional well-being initiatives often fail to address this systemic challenge, particularly in industrial contexts. This study introduces the Human Energy Management System (HEMS), a strategic framework to develop, implement, and refine strategies for optimizing workforce energy. Grounded in Industry 5.0’s human-centric, resilient, and sustainable principles, HEMS integrates enterprise risk management (ERM), design thinking, and the Plan-Do-Check-Act (PDCA) cycle. Employing a qualitative Design Science Research (DSR) methodology, the study reframes human energy depletion as an organizational risk, providing a proactive, empathetic, and iterative approach to mitigate workplace stressors. The HEMS framework is developed and evaluated through theoretical modeling, literature benchmarking, and secondary case studies, rather than empirical testing, aligning with DSR’s focus on conceptual validation. Findings suggest HEMS offers a robust tool to operationalize human energy reinforcement strategies in industrial settings. Consistent with the European Union’s vision for human-centric industrial transformation, HEMS enables organizations to foster a resilient, engaged, and thriving workforce in both stable and challenging times. Full article

Traumatic brain injury (TBI) is a major neurological condition affecting millions of individuals each year. Mild TBI (mTBI) manifests differently, with some individuals experiencing persistent, debilitating symptoms while others recover more rapidly. Despite its classification as “mild,” mTBI leads to both short- and long-term neurological effects, many of which occur due to functional changes in the brain. TBI-induced environmental changes within the brain play a critical role in shaping these functional outcomes. The importance of astrocytes in maintaining central nervous system (CNS) homeostasis has been increasingly recognized for their pivotal role in the brain’s response to TBI. Previous studies showed significant TBI-associated metabolic dysregulations. Therefore, we sought to analyze how astrocytes might adapt to persistent metabolic stressors in the post-injury microenvironment and identify injury-induced shifts occurring in vivo that may contribute to chronic metabolic dysfunction. We used an astrocyte-specific genome-scale metabolic model that allowed for the input of biologically relevant uptake rates corresponding to healthy astrocytes to analyze how the activity of metabolic pathways differed in hypoxic and acidic conditions. Additionally, these fluxes were integrated with mass spectrometry-based proteomics from male Sprague-Dawley rats subjected to mTBI to identify chronic adaptive neural responses post-injury. Comparison of modeled metabolic fluxes and experimental proteomic data demonstrated remarkable alignment, with both predicting significant changes in key metabolic processes including glycolysis, oxidative phosphorylation, the TCA cycle, and the Pentose Phosphate Pathway. These overlapping signatures may represent core survival strategies, offering insight into metabolic priorities and potentially serving as biomarkers of injury adaptation or recovery capacity. Full article

Crowding stress is an inevitable stressor in intensive farming, yet its underlying mechanisms are still obscure, severely hindering the aquaculture industry’s healthy development. As the primary sensory and regulatory organ for stressors, the brain plays a crucial role in stress responses. In this study, the effect of crowding stress on the telencephalon (Tel) and hypothalamus (Hy) has been explored using RNA sequencing. After four weeks of crowding stress, neuroinflammation-related genes were significantly induced in both the Tel and Hy. Additionally, cell fate-related processes were markedly altered. Neurogenesis-related pathways, including the Wnt and Hedgehog signaling pathways, were significantly enriched in both regions. The apoptosis-related genes (caspase3, p53) were predominantly downregulated in the Tel (log₂Fold Change: −1.27 and −0.71, respectively), while ferroptosis-related genes (ho1, ncoa4) were specifically activated in the Hy (log₂Fold Change: 1.15 and 0.73, respectively). The synaptic plasticity-related genes (prkcg, cacna1d) were significantly downregulated in both the Tel (log₂Fold Change: −1.78 and −0.88) and Hy (log₂Fold Change: −1.99 and −1.52). Furthermore, neurotransmitter synthesis (γ-aminobutyric acid (GABA) and serotonin (5-HT)) was disrupted in the Tel, whereas growth-related hormone gene expression was markedly altered in the Hy. These findings provide novel insights into the neurobiological mechanisms of chronic crowding stress in fish, laying a foundation for developing brain-targeted strategies to enhance welfare and mitigate stress in intensive largemouth bass farming. Full article

Exposure to chronic stress creates vulnerability to drug misuse and presents a barrier to sustained recovery for many individuals experiencing substance use disorders (SUDs). Preclinical literature demonstrates that stress modulates psychostimulant intake and seeking, yet there are wide gaps in our understanding of the specific mechanisms by which stress promotes brain changes that may govern addiction-related behaviors. Recent data suggest that microglia, innate immune cells in the central nervous system, are highly responsive to chronic stressors, and several mechanistic links have been explored highlighting the critical role microglia play in stress-related brain adaptation. Importantly, psychostimulants may engage similar microglial machinery, which opens the door for investigation into how microglia may be involved in shaping motivation for psychostimulants, especially in the context of stress exposure. The aims of this review are threefold: 1. Offer a brief overview of microglial biology in the adult brain. 2. Review current methods of interrogating microglial function with a focus on morphometric analyses. 3. Highlight preclinical research describing how microglia contribute to brain changes following chronic stress and/or psychostimulant exposure. Ultimately, this review serves to prime investigators studying the intersection of stress and SUDs to consider the relevant impacts of microglial actions. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) and Parkinson’s disease (PD) are two highly prevalent chronic conditions that often coexist in older adults. Their interaction may influence clinical outcomes, particularly during external stressors such as the COVID-19 pandemic. This study aimed to assess the prevalence and temporal trends of PD among hospitalized patients with T2DM in Spain (2017–2023), evaluate sex-based differences in clinical characteristics and outcomes, examine the impact of the COVID-19 pandemic, and identify predictors of PD diagnosis and in-hospital mortality (IHM). Methods: We conducted a retrospective, nationwide study using the Spanish National Hospital Discharge Database (RAE-CMBD). Adults aged ≥40 years hospitalized with T2DM were included. PD cases were identified using ICD-10 codes. Joinpoint regression assessed temporal trends, and multivariable logistic regression identified factors associated with PD and IHM. Results: Among 5.1 million T2DM-related hospitalizations, 107,931 (2.41%) involved PD. PD prevalence increased over time, particularly among women. Men accounted for most PD cases and were younger than their female counterparts. Depression and anxiety were more frequent in women and associated with PD in both sexes. IHM peaked at 14.6% in 2020, coinciding with the COVID-19 outbreak. Predictors of IHM included older age, higher comorbidity burden, dementia, and COVID-19 diagnosis. Conclusions: The coexistence of PD and T2DM in hospitalized patients is associated with clinical complexity and increased mortality. Personalized, multidisciplinary care is essential to address sex-specific patterns, psychiatric comorbidities, and vulnerability to systemic stressors. Full article

Background/Objectives: Adolescents with chronic physical health conditions (CHCs) use specific coping strategies to respond to condition-related stressors. However, most studies of CHC-related stress and coping focus on a single condition. The objective of this study was to measure CHC-related stress and identify associated coping strategies in adolescents with a variety of CHCs. A secondary objective was to examine the relationship between CHC-related stress, coping strategies, health-related quality of life, and perceived severity of chronic illness. Methods: Teens (n = 38, 68.42% female, mean age 17.9 years) with CHCs completed the Responses to Stress Questionnaire (RSQ) for CHC-related stress, the PedsQL to assess health-related quality of life, and the Perceptions of the Severity of Chronic Illness (PSCI) measure. The most frequently reported conditions were asthma, food allergies, and multiple conditions. We used fuzzy cluster analysis to identify two clusters, high stress and low stress, based on ratings of CHC-related stressors. Relationships between coping strategies and the PedsQL and PSCI, and between the PSCI and PedsQL, were assessed using Pearson partial correlations. Relationships between the PSCI, PedsQL, and coping strategies for the two clusters were assessed using adjusted mean differences. We adjusted for multiple comparisons by controlling the false discovery rate. Significance was set at p < 0.05. Results: Teens were most likely to use secondary control engagement coping and involuntary engagement to respond to CHC-related stressors. Teens in the two clusters differed on health-related quality of life but not coping strategies or perceived condition severity. CHC diagnosis category was associated with cluster membership. Conclusions: This exploratory study highlighted relationships among quality of life, coping strategies, and CHC diagnosis category that should be explored in future studies. Improved understanding of CHC-related stress and coping strategies in teens with CHCs could have an impact on their quality of life and well-being. Full article