Search Results (12,990)

Atrial cardiomyopathy (ACM) is defined as any complex of structural, architectural, functional, electrophysiological, and molecular changes affecting the atria that may result in clinically significant health consequences. ACM can be caused by a variety of factors, including age-related changes, valvular or vascular disease, genetic diseases, congestive heart failure, metabolic diseases, cardiovascular disease (CVD) risk factors such as arterial hypertension (AH) or obesity, obstructive sleep apnea, and other infectious or noninfectious diseases predisposing to chronic inflammation. The diagnosis of ACM relies on several modalities, including electrocardiography, echocardiography, cardiac magnetic resonance imaging (MRI), computed tomography (CT), electroanatomical mapping (EAM), genetic studies, and biomarkers, which can detect and characterize structural, mechanical, and electrical atrial dysfunction. These changes often include structural atrial remodeling (fibrosis), abnormal structure of the atrial wall and its components, and contractile and electrical dysfunctions. When assessing aspects of ACM, structural changes in the atria such as left atrium (LA) size and fibrosis; LA architectural changes such as the expression of remodeling; changes in LA mechanics such as echocardiographic stress indices; changes in reservoir function and changes in contraction; biological factors determining changes in biomarkers; possible genetic predispositions and higher expression of certain genes encoding certain proteins; and arrhythmogenic factors associated with a higher risk of atrial fibrillation (AF) and stroke and a worse short- and long-term prognosis are very important. When considering the challenges of diagnosing ACM, it should be noted that without standardized diagnostics, most ACM diagnostic situations remain primarily research tools rather than practical clinical diagnostic methods. This review critically evaluates the evidence and translational gaps in the diagnosis of ACM, synthesizing the emerging role of advanced diagnostics and their clinical and prognostic implications as a key future tool for individual risk stratification. Full article

Background: Oral lichen planus is a chronic oral potentially malignant disorder requiring timely diagnosis and long-term follow-up, yet its diagnostic pathway remains poorly characterised. This study assessed diagnostic and follow-up intervals in patients with oral lichen planus and explored associated clinical and healthcare-related factors. Methods: This retrospective cohort study included 199 patients with clinically and histopathologically confirmed oral lichen planus managed at the Oral Medicine Unit of the University of Murcia. Diagnostic time points were defined using an adapted Aarhus framework. Patient, primary care, specialist diagnostic and total intervals were analysed using multivariable quasi-Poisson regression. Loss to follow-up was assessed using Cox regression. Results: Older age was associated with longer patient, primary care and total intervals. Women had a shorter patient interval than men (IRR = 0.44; 95% CI: 0.21–0.91; p = 0.03), but a longer primary care interval (IRR = 3.09; 95% CI: 1.12–10.2; p = 0.04). Compared with erosive oral lichen planus, mixed and reticular forms showed shorter primary care intervals and shorter specialist diagnostic intervals, with IRRs ranging from 0.21 to 0.36 (all p < 0.01). Daily alcohol consumption was associated with the longest total interval. Older age was associated with a higher risk of loss to follow-up (HR = 1.02; 95% CI: 1.00–1.04; p = 0.01), whereas non-pharmacological treatment was associated with a lower hazard of loss to follow-up (HR = 0.31; 95% CI: 0.16–0.60; p < 0.001). Conclusions: Diagnostic delay in oral lichen planus is multifactorial and appears to depend on patient characteristics, clinical presentation and healthcare pathway factors. Improved recognition of erosive disease, clearer referral criteria and structured follow-up strategies may enhance care continuity. Full article

Aortitis—inflammation of the aortic wall—presents at the interface of vasculitis, infection, structural aortic disease, and cardiovascular risk. It may occur in giant cell arteritis (GCA), Takayasu arteritis, immunoglobulin G4 (IgG4)-related disease, drug-induced injury, infection, or as an isolated finding after aortic surgery. Modern imaging detects aortic inflammation more frequently, but the main challenge is classification rather than detection: determining whether disease is infectious or immune-mediated, active or dominated by fixed structural damage, systemic or isolated, and whether the dominant threat is aneurysm, dissection, undertreated infection, or avoidable immunosuppression. This review considers aortitis as a high-risk vascular syndrome requiring aetiology-first classification rather than descriptive labelling. Before escalating immunosuppression, infection must be actively excluded and inflammatory activity distinguished from fixed vascular damage. Treatment should be individualised according to phenotype, age, vascular territory, comorbidity, and toxicity risk, with surveillance continuing even after symptoms and inflammatory markers improve. Optimal care depends on multidisciplinary assessment integrating rheumatology, infectious diseases, vascular surgery, radiology, and cardiology expertise. Progress will require standardised imaging definitions, registries linking inflammatory control with structural vascular outcomes, and validation of artificial intelligence (AI) tools before clinical adoption. Full article

Background/Objectives: Studies consistently demonstrate that microprocessor-controlled prosthetic knees (MPKs) improve mobility and quality of life for people with lower limb loss or absence by enhancing balance and reducing falls. However, the extent to which these benefits apply across demographic groups remains unclear. Therefore, we conducted a literature review to evaluate how representative and transferable research on MPKs is across different populations, and which factors influence this. Methods: Using systematic review principles and PRISMA guidelines, 27 studies were analysed from databases including Cochrane, CINAHL, MEDLINE, and PubMed, as of 20th September 2025. The included studies primarily focused on young-to-middle-aged adults, men, individuals with trauma-related amputation, and higher mobility levels. Results: We found that older adults, women, and individuals with amputation caused by vascular disease or diabetes were under-represented in MPK research. Moreover, variability in time since amputation complicates the generalisability of findings, as this factor significantly influences adaptation and functional outcomes. Conclusions: While evidence supports MPKs’ effectiveness in enhancing mobility and reducing the risk of falls, their benefits may not fully apply to under-represented groups, such as older adults, women, or low-activity users. Future research should prioritise more diverse participant samples to improve the generalisation of MPK outcomes across different demographics and functional levels. Full article

Background: Single-access transfemoral transcatheter aortic valve implantation (TAVI) reduces the need for multiple vascular access and therefore, the related risk of related complications. However, the impact of patient age on its clinical outcomes remains uncertain. Methods: This is a secondary analysis of previously reported propensity score matched study comparing clinical outcomes of single- versus dual-access transfemoral TAVI using SAPIEN-3-Ultra. We examined the relation between patient age, access strategy and outcomes—specifically, 30-day safety endpoint according to the Valve Academic Research Consortium 3 (VARC-3) and major adverse cardiovascular events (MACE), defined as death, permanent pacemaker, neurological or vascular complications—using logistic regression interaction analyses, and restricted cubic spline modelling. Results: A total of 204 patients (propensity score-matched cohort) were included in the study. The elderly group were more likely to have hypertension, peripheral vascular disease or stroke. The use of single access was comparable. The elderly cohort demonstrated a tendency toward longer fluoroscopy and procedural times compared with the non-elderly group. This pattern likely reflects the greater technical complexity and heightened procedural caution often associated with older patients, including more challenging vascular anatomy and the need for careful device handling. Although not statistically significant, these findings remain clinically meaningful and are consistent with the notion that procedures in elderly patients frequently require more meticulous planning and execution. There was a significant interaction between access strategy and age in reducing MACE, but not in VARC-3 safety outcomes. Single access was associated with a significant reduction in MACE (5.4% vs. 26.7%, p = 0.015) with comparable technical and safety outcomes when compared with elderly patients who underwent dual-access TAVI. Conclusions: Single-access TAVI was linked to favourable early outcomes, maintained procedural success, and suggested a possible age-dependent pattern in the occurrence of MACE. Our findings support the need for randomised studies to demonstrate superiority of single- versus dual-access TAVI, particularly in the elderly population. Full article

In modern societies, the renewed concept of food as medicine coexists with unprecedented consumption of highly processed foods, food additives, environmental xenobiotics, and pharmacological agents, contributing to the increasing prevalence of metabolic and degenerative diseases and accelerated aging. Although modern pharmacotherapies have transformed disease management, long-term drug exposure introduces additional metabolic burdens, off-target effects, and cumulative toxicities that are profoundly influenced by nutritional status. Collectively, dietary constituents, environmental chemicals, endogenous metabolic by-products, and therapeutic agents constitute a complex exposome that requires continuous recognition, utilization, detoxification, and clearance. Within this context, the liver sinusoidal clearance system (LSCS) emerges as a central regulator of systemic homeostasis. We propose a conceptual framework in which circulating molecules are classified as self (S), modified self (M), and foreign (F) molecules according to their physiological handling by the LSCS. Through coordinated hepatic utilization of S molecules and selective clearance of M and F molecules, fenestrated liver sinusoidal endothelial cells (LSECs) maintain metabolic homeostasis, immune tolerance, and physiological pharmacokinetics. Conversely, chronic dietary overload, poor dietary quality, food processing, and sustained exposure to pro-inflammatory and oxidative dietary and environmental molecules initiate chronic low-grade inflammation, which promotes LSEC capillarization, impairs hepatic clearance, increases the modification of S molecules into M molecules and establishes a feed-forward cycle that further amplifies chronic inflammation and metabolic dysfunction. Finally, we discuss recent advances in the programmable modulation of the LSCS, including its transient suppression to prolong therapeutic exposure and its activation to enhance the clearance of metabolically harmful M and F molecules through coordinated upregulation of the endoglin–stabilin-2–FcγRIIb axis and the LSEC markers Oit3 and Dnase1L3. We highlight dual-function supramolecular nanofiber platforms that enable bidirectional regulation of the LSCS through nanofiber complexes with therapeutic proteins, thereby expanding their therapeutic potential and enhancing efficacy in the treatment of metabolic, inflammatory, and age-related diseases. Full article

Per- and polyfluoroalkyl substances (PFAS) are environmental contaminants associated with higher serum lipids, although primarily in cross-sectional studies, limiting causal inference. We aim to determine whether there is a causal relationship between PFAS and serum lipid levels by emulating a target trial of a hypothetical PFAS-reduction intervention using observational data. The target trial would enroll adults aged ≥20 years without prior cardiovascular, kidney, or liver disease, diabetes, or use of related medications. Participants would be randomly assigned to either PFAS-reduction counseling or no counseling, with adherence evaluated after 10 years, and then followed up after 10 years to assess effects on serum lipids. To emulate the target trial, we will use data from the Copenhagen City Heart Study on three successive clinical visits: baseline, follow-up, and outcome assessment visit, 10 years apart. Eligible participants meet the target trial criteria, have available blood samples for PFAS quantification at follow-up, and information on serum lipids at the outcome assessment. Intervention strategies will be evaluated based on observed reductions in PFAS concentrations between baseline and follow-up visit. Serum lipids are assessed at the outcome assessment visit. The emulation assumes exchangeability by adjusting for baseline and time-varying confounders using G-computation. This protocol explores applying the target trial emulation framework to improve causal inference in environmental epidemiology. Full article

Background: Although numerous magnetic resonance imaging (MRI) findings have been described in idiopathic intracranial hypertension (IIH), the potential contribution of craniocervical junction morphology to disease pathophysiology and diagnosis remains largely unexplored. This study aimed to evaluate foramen magnum morphology and cerebrospinal fluid (CSF) spaces at the craniocervical junction in patients with IIH and to investigate their associations with disease severity and diagnostic performance. Methods: In this retrospective case–control study, 70 patients diagnosed with IIH according to the modified Dandy criteria and 70 age- and sex-matched controls were included. Brain MRI examinations were retrospectively reviewed. Optic nerve sheath diameter, optic nerve tortuosity angle, foramen magnum anteroposterior and transverse diameters, foramen magnum area, foramen magnum index, and anterior and posterior subarachnoid CSF spaces were measured. Correlation analyses with lumbar puncture opening pressure and papilledema grade were performed. Independent imaging predictors of IIH were identified using multivariable logistic regression analysis, and diagnostic performance was assessed using receiver operating characteristic (ROC) analysis. Results: Compared with controls, patients with IIH demonstrated significant alterations in craniocervical junction morphology, including smaller foramen magnum anteroposterior diameter, foramen magnum area, foramen magnum index, and anterior subarachnoid CSF space, together with increased optic nerve sheath diameter and reduced optic nerve tortuosity angle (all p < 0.001). Foramen magnum morphometric parameters and anterior subarachnoid CSF space were significantly associated with both lumbar puncture opening pressure and papilledema grade. Multivariable logistic regression identified optic nerve sheath diameter (OR = 2.143, p = 0.002), optic nerve tortuosity angle (OR = 0.925, p < 0.001), and foramen magnum index (OR = 0.526 per 0.1-unit increase, p = 0.001) as independent imaging predictors of IIH. The combined prediction model demonstrated excellent diagnostic performance (AUC = 0.901), with 81.4% sensitivity and 87.1% specificity. Conclusions: Craniocervical junction morphometric features and subarachnoid CSF spaces at the foramen magnum differed between patients with IIH and controls and may provide complementary imaging information. These cross-sectional associations do not establish whether the observed differences are pre-existing anatomical characteristics or secondary changes related to chronically elevated intracranial pressure. Prospective multicenter studies incorporating dynamic CSF-flow imaging are warranted to validate these findings and clarify the temporal relationship between these morphometric features and disease development. Full article

Background/Objectives: Outcomes after perioperative FLOT for gastric and gastroesophageal junction adenocarcinoma remain variable, even among patients treated with curative intent. Although postoperative pathological findings are central to risk assessment, they do not fully capture patient-related factors that may influence recovery, treatment completion, and survival. This multicenter study evaluated routinely available clinical, laboratory, and pathological variables and assessed whether integrating these variables could improve postoperative prognostic stratification. Methods: We retrospectively analyzed 173 patients with locally advanced gastric or gastroesophageal junction adenocarcinoma treated with perioperative FLOT across seven oncology centers in Türkiye. Overall survival (OS) was the primary endpoint. Baseline inflammatory/nutritional status, pretreatment carcinoembryonic antigen (CEA), postoperative nodal status, and comorbidity burden were assessed. An exploratory modified FLOT Prognostic Score (mFPS) was constructed by assigning one point each for high inflammatory/nutritional risk, elevated CEA, ypN-positive disease, and age-adjusted Charlson Comorbidity Index ≥ 5. Results: At a median follow-up of 39.7 months, median OS was 41.4 months, with estimated 2-year and 5-year OS rates of 69% and 44%, respectively. Surgery was performed in 164 patients, and 83 patients completed planned adjuvant chemotherapy. In multivariable analysis, ypN-positive disease, higher comorbidity burden, and high inflammatory/nutritional risk were independently associated with shorter OS. Among the 126 patients with complete data available for all score components, the mFPS stratified patients into groups with significantly different outcomes: median overall survival was not reached in the low-risk group, compared with 56.1 months in the intermediate-risk group and 18.7 months in the high-risk group. Conclusions: Survival after perioperative FLOT was not determined by residual disease burden alone. Integrating postoperative nodal status with baseline host-related factors may help identify patients at increased risk of adverse outcomes following curative-intent treatment. The proposed score should be considered exploratory and requires external validation before clinical application. Full article

Background/Objectives: Sleep disturbances are common but frequently underrecognized in multiple sclerosis (MS), independently predicting reduced quality of life and worsening fatigue, cognitive impairment, and depression. While pain, nocturia, fatigue, and mood symptoms are established contributors, cardiometabolic, and inflammatory factors remain largely unexplored despite their known links to poor sleep in other populations. This study used interpretable machine learning to determine the relative contribution of disease-related, cardiometabolic, and inflammatory parameters to sleep quality, assessed by the PSQI, in patients with MS. Methods: This cross-sectional, observational, single-center cohort study enrolled adult patients with MS. Sleep quality (PSQI), daytime sleepiness (ESS), and restless legs syndrome severity (IRLS) were assessed alongside clinical, anthropometric, hemodynamic, and laboratory parameters, including inflammatory and metabolic indices. Three regression models, Support Vector Regression (SVR), Random Forest, and XGBoost, were trained on 28 predictors to predict PSQI global scores and evaluated on an internal test set, with feature contributions examined using SHAP analysis. Results: A total of 173 patients with MS were included (mean age 39.66 ± 11.86 years, 69.9% female, 90.2% RRMS), with 48.0% classified as poor sleepers (PSQI > 5) and a mean PSQI score of 6.06 ± 3.47. XGBoost achieved the best predictive performance (test R² = 0.451). SHAP analysis identified IRLS severity as the strongest predictor of PSQI across all three models, followed by EDSS score and depression in the Random Forest and XGBoost models, while daytime sleepiness (ESS) ranked consistently among the top predictors. Cardiometabolic and inflammatory parameters contributed inconsistently, with several showing effects opposite to physiological expectation. Conclusions: Sleep impairment in MS was most strongly associated with restless legs syndrome severity and neurological disability, with depression also contributing in the two best-performing models. Disease-related and symptomatic factors outweighed cardiometabolic and inflammatory contributions. These findings support the value of interpretable machine learning for identifying clinically relevant correlates of sleep quality in MS, though the exploratory design and modest sample size warrant confirmation in larger, independent cohorts. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) is a metabolic disorder associated with an amplified risk of unfavorable pregnancy outcomes. This study aimed to compare clinical characteristics and pregnancy outcomes among GDM patients belonging to different ethnic groups. Patients and Methods: This retrospective analysis included n = 466 women with GDM (n = 167 Asian; n = 299 European). The impact of ethnicity on pregnancy outcomes was evaluated using multivariable logistic regression models, adjusting for confounding factors. Results: Asians were younger than Europeans (p < 0.001) and more frequently multiparous (p = 0.003). Fasting glucose at OGTT was higher in Asians, as well as HbA1c values at the end of pregnancy (p = 0.010 and p = 0.001, respectively). Asian ethnicity was associated with an increased likelihood of insulin therapy (OR = 3.36 [1.72–6.58] 95% CI, p < 0.001), in the adjusted model. The gestational week of delivery was lower in Asians compared to Europeans (p = 0.007). The Asian group had a higher occurrence of cesarean section (p = 0.048) and emergency cesarean section (p = 0.006) compared to the European group. Delivery complications were more frequent in the Asian cohort, adjusting for confounders (OR = 2.19 [1.11–4.32] 95% CI, p = 0.023). Newborns of the Asian group were more frequently small for gestational age (SGA) in adjusted models (OR = 2.36 [1.08–5.15] 95% CI, p = 0.031). Conclusions: Worse GDM outcomes were observed in the Asian cohort compared to the European cohort. Identifying risk factors for GDM-related complications is crucial for developing tailored interventions and reducing the overall disease burden. Full article

Advances in healthcare have led to substantial growth in the global population of cancer survivors, yet young adult cancer survivors (YACS) aged 18–39 years remain an underrepresented population in cancer survivorship research. This review examines the health challenges and psychosocial factors that shape nutritional status in YACS, with the aim of informing age-appropriate nutritional care. YACS face significant financial and psychosocial demands unique to this life stage, balancing education, early careers and family responsibilities. They report greater unmet nutritional and health needs than other age cohorts, in addition to concerns regarding long-term side effects, financial strain, fear of cancer recurrence and increased responsibility for managing their own care. Cancer treatment can cause nutrition impact symptoms (e.g., nausea, taste changes, fatigue, dysphagia and gastrointestinal (GI) disturbances) that may persist for years, and YACS are vulnerable to late effects such as endocrine dysfunction, cardiometabolic disease, chronic pain and osteoporosis, all of which can be influenced by diet. Poor dietary patterns have been observed in YACS, indicating low intakes of fruits, vegetables, fibre and dairy, and higher consumption of saturated fat, sodium and processed foods. This narrative review evaluated fourteen nutritional intervention studies targeting YACS aged 18–39. Most existing interventions demonstrate minimal recruitment and retention rates, small sample sizes, and a reliance on self-report methods rather than objective nutritional measures. These limitations highlight the need for a deeper understanding of YACS’ specific nutritional needs and more effective strategies to engage this cohort. Future research should prioritise larger, more representative samples, incorporate objective nutritional and clinical measures, and explicitly address psychosocial and age-related barriers to healthy eating in young adulthood. Full article

Cardiovascular disease remains the leading cause of death among women, yet female cardiovascular risk continues to be underrecognized, and women remain underrepresented in many cardiovascular trials. Sex-related differences in hormonal exposure, immune regulation, vascular function, pregnancy-related conditions, and clinical presentation contribute to heterogeneity in cardiovascular disease across the life course. Statins reduce atherosclerotic cardiovascular events in women and men, with no consistent evidence of treatment-effect heterogeneity by sex. In addition to lowering low-density lipoprotein cholesterol, statins influence inflammatory signaling, endothelial nitric oxide bioavailability, oxidative stress, thrombosis, and plaque biology. These effects are biologically relevant to atherosclerosis; however, current clinical evidence does not establish that LDL-independent statin effects confer a uniquely greater benefit in women. Historical pathological studies suggested that plaque erosion may contribute relatively more often to acute coronary thrombosis in selected younger women, whereas contemporary optical coherence tomography studies show similar overall frequencies of plaque rupture and erosion between sexes and important age-related variation. Evidence for a female-specific effect of statins on post-myocardial infarction remodeling, cognition, or pharmacogenomic susceptibility is also insufficient. This narrative review distinguishes established clinical evidence from mechanistic plausibility and unresolved sex-specific hypotheses. It emphasizes equitable implementation of guideline-directed lipid-lowering therapy, careful evaluation of statin-associated symptoms, and the need for adequately powered studies reporting sex-stratified estimates and formal treatment-by-sex interactions. Full article

Background/Objectives: In Lebanon, the economic crisis since 2019 has severely strained healthcare infrastructure, yet its impact on cancer treatment adherence remains incompletely characterized. This study assessed factors associated with treatment delay and regimen modification to identify barriers to optimal cancer care among Lebanese patients. Methods: This multicenter, cross-sectional study was conducted in five tertiary hospitals in Beirut, Lebanon, between 13 June 2024, and 27 June 2025. Demographic, clinical and treatment data were collected via a structured questionnaire. Bivariate and multivariable binary logistic regression analyses were performed to identify independent predictors of treatment delay (>2 weeks) and incomplete treatment regimens. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) are reported. Results: A total of 244 patients were enrolled in the study. The study population was predominantly female (59.0%) and aged ≥60 years (60.2%). Advanced disease was common, with 50.4% of patients presenting with stage IV disease. Financial vulnerability was widespread: 72.6% reported monthly household incomes below USD 1000, 88.1% reported a decline in income due to the economic crisis, and 39.3% relied on unstable income sources. Overall, 52.5% of patients experienced treatment initiation delays, and 9.0% received incomplete or dose-reduced regimens. On multivariable analysis, reliance on unfixed income independently predicted treatment delay (aOR 2.55, 95% CI 1.42–4.59; p = 0.002), lack of health insurance (aOR 1.91, 95% CI 1.08–3.39; p = 0.026) and pre-treatment surgical costs also increased the odds of delay (aOR 9.03, 95% CI 2.57–31.7; p = 0.001). For incomplete treatment, unfixed income remained an independent predictor (aOR 2.09, 95% CI 1.16–5.79; p = 0.015). A lack of insurance (aOR 5.62, 95% CI 1.22–25.9; p = 0.027) and high laboratory costs (>USD 150 per session) were also associated with incomplete regimens (aOR 1.62, 95% CI 1.02–2.57; p = 0.041). Conclusions: In Lebanon’s crisis context, financial instability was a key factor associated with deviations in cancer treatment. These findings highlight the need for strengthened insurance coverage and subsidization of diagnostic and treatment-related costs to ensure timely and continuous oncologic care. Full article

Chronic stress is increasingly recognized as a major contributor to systemic disease. Prolonged or repeated activation of the hypothalamic–pituitary–adrenal (HPA) axis and sympathoadrenal systems may contribute to glucocorticoid receptor resistance and chronic low-grade inflammation, although stress-related responses vary depending on stressor characteristics, population, age, sex, health status, and study design. Elevated levels of pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), oxidative stress, and NF-κB activation contribute to immune dysfunction, neuroinflammation, metabolic disturbances, reproductive and endocrine imbalance, as well as structural and functional alterations in stress-sensitive brain regions. Prolonged exposure to stress may contribute to the development of neuropsychiatric, cardiovascular, metabolic, neurodegenerative, and malignant diseases, highlighting the need for effective strategies to mitigate the detrimental consequences of chronic stress. Given the limitations and adverse effects associated with conventional pharmacological approaches, increasing attention has been directed toward natural bioactive compounds. Terpenes represent a diverse class of phytochemicals with reported anti-inflammatory, antioxidant, and neuromodulatory properties. Terpenes such as limonene and β-caryophyllene, as well as terpenoids such as linalool, may modulate NF-κB, MAPK, and Nrf2 signaling pathways and interact with the endocannabinoid system, thereby attenuating neuroinflammation, oxidative stress, and stress-induced immune dysregulation. This review summarizes current evidence regarding the mechanisms linking chronic stress, HPA axis dysfunction, and systemic disease, with particular emphasis on endocrine, immune, and nervous system alterations. In addition, it critically evaluates the mechanistic and translational potential of terpenes as possible indirect neuroimmune and redox modulators of stress-related pathophysiology. Full article