Search Results (5,942)

Background: The contribution of oral inflammatory conditions to systemic disease burden remains underexplored within multimorbidity frameworks. Emerging evidence suggests that periodontal inflammation may play a role in the clustering of chronic diseases, yet few studies have evaluated this at a population level using robust datasets. The aims of this study were to investigate whether periodontal diseases are associated with Multiple long-term conditions (MLTCs) burden and severity in two population-based cohorts and to examine whether systemic inflammatory biomarkers mediate these associations. Materials and Methods: We analyzed two population-based cohorts: the UK Biobank (UKB; n = 500,612) and the US National Health and Nutrition Examination Survey (NHANES; n = 10,714). MLTCs were defined as the coexistence of ≥2 chronic diseases. Associations between periodontal diseases and MLTCs were assessed using multivariable logistic and multinomial logistic regression. Causal mediation analyses examined the contribution of systemic inflammatory markers. Results: Approximately half of all participants had MLTCs. The prevalence of periodontal diseases was 17.8% in UKB (self-reported symptoms), and 42.3% in NHANES (clinically assessed). Periodontal diseases were independently associated with greater odds of MLTCs in both UKB (OR 1.12; 95% CI 1.10–1.14) and NHANES (OR 1.22; 95% CI 1.09–1.37). Associations were stronger among adults aged ≤ 60 years. A consistent dose-response relationship was observed between periodontal status and the number and severity of chronic conditions, as well as inflammatory-related MLTCs. Mediation analyses suggested partial effects through white blood cell count, neutrophils, and C-reactive protein. Conclusions: Periodontal inflammation is independently associated with greater multimorbidity burden, particularly in younger adults. Systemic inflammation may offer a plausible biological link, and these findings position oral health as an underrecognized and modifiable target in multimorbidity prevention and management frameworks, warranting prospective investigation. Full article

Fabry disease is an X-linked lysosomal storage disease that leads to the intracellular accumulation of glycosphingolipids in many tissues and fluids, including the kidneys. We report a single family with Fabry disease that includes seven patients carrying the pathogenic variant c.797A>C in the GLA gene, with remarkable variability in kidney involvement, assessed based on clinical, biological, and histological data. The patients were monitored for 2–9 years, and all received enzyme replacement therapy. Kidney involvement was variable and included severely decreased GFR with significant proteinuria, mildly to moderately decreased GFR with proteinuria, mildly decreased GFR with microalbuminuria or normoalbuminuria, hyperfiltration with normoalbuminuria, and preserved kidney function. All patients who underwent kidney biopsy presented with Fabry-specific lesions and, in some cases, chronic histological damage. This study provides valuable insights into kidney involvement evaluated through kidney biopsy, personalized management strategies for family members according to their phenotype, and long-term follow-up of kidney function. We underscore the importance of molecular screening of the GLA gene in all family members for early identification of the disease and early initiation of specific treatments that can prevent or delay the progression of this disease. Full article

Background: Cardiovascular complications are the leading cause of death in patients with end-stage renal disease (ESRD). Hemodialysis involves rapid electrolyte shifts and sudden fluid removal, which can affect ventricular repolarization and trigger arrhythmias in patients with ESRD. To enhance patient care, it is crucial to regularly assess cardiac function using noninvasive and painless methods, such as Holter electrocardiography (ECG) and routine cardiac ultrasound. These evaluations may inform improved prevention strategies to reduce the risk of elevated cardiovascular mortality rates. Methods: In total, 40 patients with ESRD on chronic hemodialysis (HD) were approached, and only 18 were enrolled from September 2024 to July 2025. Detailed medical information was provided, and written informed consent was obtained from the patient. The median duration of Holter ECG recording was 84.65 h, and cardiac ultrasound examinations were conducted. Blood gas samples were collected hourly during the second dialysis session. Results: Surprisingly, one-third of the patients opted to withdraw their consent for this painless investigation. No significant differences were observed in the QT and QTc intervals between the dialysis and non-dialysis days (p = 0.184 and p = 0.446, respectively). However, a significant increase was observed during the first 3 h of dialysis when analyzing the intradialytic period. Conclusion: Some patients showed clinically significant changes in QT and QTc intervals during treatment, which could not be confirmed statistically. Although we did not formulate a hypothesis, it is essential to recognize that patient compliance significantly influences the cardiovascular outcomes of individuals undergoing hemodialysis. Full article

The pancreas is an organ with two functions: endocrine and exocrine. The proper functioning of the pancreas depends on many factors. One of these is trace elements—precise control of trace element homeostasis is important for both the endocrine and exocrine parts. This review provides a comprehensive summary of current knowledge regarding the role of trace elements: iron (Fe), copper (Cu), cobalt (Co), iodine (I), manganese (Mn), zinc (Zn), silver (Ag), cadmium (Cd), mercury (Hg), lead (Pb), and selenium (Se) in pancreatic physiology and their influence on the pathogenesis of key diseases of this organ, such as diabetes (DM), acute (AP) and chronic pancreatitis (CP), autoimmune pancreatitis (AIP), and pancreatic cancer (PC). Trace elements, including Fe, Cu, Zn, Se, and Mn, play a fundamental role in maintaining endocrine and exocrine homeostasis, participating in insulin synthesis, stabilizing digestive enzymes, and the functioning of antioxidant systems. It has been demonstrated that disturbances in their concentrations lead to the activation of pathological molecular pathways, including oxidative stress, chronic inflammation, and beta-cell apoptosis. In the context of diabetes, excess Fe promotes ferroptosis, whilst exposure to heavy metals such as Cd, Pb, and Hg induces insulin resistance and pancreatic islet dysfunction. In the course of pancreatitis, elements such as Zn and Se exhibit protective potential by stabilizing tissue barriers, whereas toxic metals impair ion transport, exacerbating fibrotic processes. Furthermore, analysis of available data indicates a significant association between heavy metal accumulation and pancreatic carcinogenesis, driven by DNA damage and oncogene modulation. Understanding pancreatic metallomics opens new prospects for early diagnosis, environmental prevention, and the development of targeted therapeutic strategies that restore the body’s micronutrient balance. Full article

Hepatocellular carcinoma (HCC) incidence in Texas is 45% higher than the national average, with disproportionate burden among the Hispanic/Latino population. Despite significant health disparities, comprehensive evidence on HCC risk factors specific to this population remains limited. This scoping review of 20 primarily observational studies utilized PubMed, EbscoHost, and the PRISMA-ScR checklist to map risk factors in south Texas. Results show that metabolic dysfunction, specifically diabetes and obesity, increases advanced liver disease odds by 7- to 12-fold compared to non-Hispanic groups. Environmental exposures are also significant: aflatoxin was detected in 5.7 to 7.3% of Hispanic/Latino HCC tumors, and cases demonstrated 6-fold higher odds of aflatoxin biomarkers, while alcohol contributed to 3.0% of cancers. Furthermore, PNPLA3 genetic variants exerted synergistic effects with obesity and heavy alcohol consumption. Among four intervention studies, strategies included low-dose calcium montmorillonite clay for aflatoxin reduction, community-health-worker-integrated chronic care, and hospital-based hepatitis screening. However, critical research gaps remain regarding multirisk factor interactions, toxin dose–response characterization, dietary interventions, and longitudinal data. These findings underscore the urgent need for culturally tailored, community-engaged prevention programs and ethnicity-specific HCC guidelines for the Texas Hispanic/Latino population to effectively address these rising health disparities. Full article

Dihydromyricetin (DHM), a naturally occurring flavanonol predominantly found in medicinal plants like Ampelopsis grossedentata, has emerged as a promising source of natural antioxidants with multi-target pharmacological activities relevant to drug discovery. DHM exhibits a strong redox-modulating capacity, effectively attenuating oxidative stress and inflammation central drivers of chronic disease pathogenesis. Beyond direct radical scavenging, DHM regulates multiple redox-sensitive and kinase-mediated signalling pathways, thereby influencing key cellular processes involved in disease initiation and progression. This review synthesizes current evidence on the therapeutic potential of DHM, critically evaluating its mechanistic basis and translational prospects, with emphasis on its dual redox-driven and kinase-mediated modes of action. We detail its roles in metabolic disorders such as diabetes, obesity, and liver diseases, neuroprotection, cardio protection, and cancer prevention, focusing on the modulation of critical networks such as AMPK, PI3K/Akt, MAPK, NF-κB, and Nrf2. The interplay between these pathways underpins DHM’s efficacy across disease models. Furthermore, we highlight structure–activity relationship (SAR) analyses and molecular modelling studies that elucidate how the flavanonol scaffold, hydroxylation pattern, and stereochemistry of DHM govern its biological activities and target engagement. Key pharmacokinetic limitations, advances in extraction techniques, bioavailability challenges, and emerging formulation strategies including advanced delivery systems are discussed to address translational hurdles. Despite compelling preclinical data, the clinical translation of DHM remains constrained by limited human studies and incomplete mechanistic resolution. This review underscores the need for integrated pharmacological studies and innovative delivery approaches to translate the multifaceted promise of DHM into viable clinical interventions. Full article

Background: Childhood cancer survival now approaches 80% in high-income countries, yet most survivors face lifelong toxicity. This review examines the interplay between treatment efficacy, relapse prevention, and therapy-related complications. Methods: Narrative synthesis of landmark pediatric oncology trials (2000–2026), including AALL1731 (blinatumomab), ELIANA/PLAT-02 (CAR T-cell), and GD2-CART01 (neuroblastoma), with comparative analysis of efficacy and toxicity. Results: In AALL1731, adding blinatumomab to chemotherapy improved 3-year disease-free survival from 87.9% to 96.0% (HR = 0.39, 95% CI: 0.27–0.56, p < 0.001), but increased sepsis from 5.1% to 14.8%. Comparison between AALL1731 (front-line blinatumomab) and ELIANA (CAR T-cell in relapsed disease) reveals that earlier immunotherapy deployment yields better outcomes: 96% DFS vs. 48% 3-year EFS, respectively. In GD2-CART01, early use (after 1–2 prior lines) achieved 89% 5-year survival vs. 43% with delayed use (HR = 0.31). Approximately 95% of survivors experience ≥1 late effect, with 60–90% carrying chronic conditions into adulthood. Conclusions: Immunotherapy transforms outcomes, but timing is critical, as earlier deployment dramatically improves survival. Toxicity remains pervasive, requiring systematic mitigation strategies. Full article

Medicinal mushrooms have become an important component of modern dietary supplementation and functional nutrition due to their diverse biological activities and long-standing use in traditional medicine. Among the most widely studied and utilized species are Ganoderma lucidum, Lentinula edodes, Grifola frondosa, Cordyceps militaris, Cordyceps sinensis, Trametes versicolor, and Inonotus obliquus. Their therapeutic potential is associated with a wide range of biologically active constituents, including polysaccharides, triterpenoids, phenolic compounds, and other secondary metabolites. Experimental and clinical studies indicate that extracts derived from these species may support immune function, modulate inflammatory responses, and exhibit antioxidant, antimicrobial, and anticancer properties. In addition to extensive in vitro and in vivo investigations, a growing number of clinical studies have evaluated the safety and potential therapeutic benefits of medicinal mushroom preparations in humans. In recent years, increasing attention has been directed toward their incorporation into nutraceutical formulations and functional foods aimed at supporting health and preventing chronic diseases. Advances in cultivation technologies and extraction methods have also contributed to improved availability and standardization of mushroom-derived products. This review provides a comprehensive overview of selected medicinal mushroom species commonly used in dietary supplements, focusing on their bioactive constituents, reported biological activities, and potential applications in contemporary medicine. Full article

Background: Nutritional literacy is a core competency for promoting healthy dietary behaviors and preventing nutrition-related chronic diseases. Standardized scales are essential for rigorous measurement and evaluation, yet the field exhibits substantial heterogeneity in concepts and measurement approaches. Methods: We systematically searched five major databases, namely Web of Science, PubMed, Scopus, Embase, and CINAHL, from their inception to October 2025. Evidence was compiled on the conceptual evolution, domain structure, scoring logic, population-specific applicability, and application scenarios of nutritional literacy scales. Results: A total of 14 nutritional literacy scales developed between 2005 and 2025 were included in the review. The structure and measurement content of these scales have progressively expanded, evolving from an early focus on basic reading and numeracy skills to become multidimensional assessment tools encompassing knowledge, skills, and behavioral practices. The target population has broadened from the general adult population to include multiple special groups, while application regions have extended from high-income Western countries to developing regions, including China and Turkey, and assessment methodologies have progressively shifted from single tests to blended objective–subjective approaches, with most scales demonstrating sound reliability and validity. These instruments are now employed for screening, intervention evaluation, dietary behavior mechanism research, and analysis of chronic disease risk. The reviewed studies indicate that nutritional literacy is generally positively correlated with healthy dietary behaviors, nutrition labeling utilization, and related health outcomes. Conclusions: Although nutritional literacy scale research has advanced with regard to conceptualization, measurement design, and applications, major gaps remain, including fragmented dimensional structures, insufficient standardization, inadequate cultural adaptation, and limited longitudinal evidence. Future work should prioritize a unified assessment framework, stronger tools for special and vulnerable populations, digital innovations for scalable measurement, and interdisciplinary and cross-national collaboration to enhance quality, practicality, and comparability and to support global nutrition promotion and public health policy. Full article

The liver circadian clock coordinates hepatic lipid metabolism, bile acid synthesis, and glucose homeostasis through interlocking transcription–translation feedback loops. Disruption of this temporal organization is increasingly recognized as a shared pathological feature across the chronic liver disease spectrum. Transcriptomic profiling alone cannot capture the full scope of circadian dysregulation. Approximately half of rhythmically abundant hepatic proteins lack correspondingly rhythmic mRNAs. Roughly 25% of hepatic phosphosites oscillate with a 24-h period. Integrating transcriptomics, proteomics, post-translational modification profiling, metabolomics, and emerging single-cell and spatial approaches is therefore necessary for an accurate account of how circadian programs are remodeled in disease. This narrative review delineates the multi-omics landscape of circadian clock dysregulation across six chronic liver disease categories. These encompass metabolic dysfunction-associated fatty liver disease (MAFLD), alcoholic liver disease (ALD), viral hepatitis, hepatocellular carcinoma (HCC), liver fibrosis, and cholestatic disease. Four molecular features recur across these contexts. BMAL1 functional downregulation, REV-ERBα oscillatory output attenuation, NAD⁺ oscillatory amplitude reduction, and gut–liver axis circadian desynchronization together constitute an inferential framework for hepatic circadian failure. These features represent recurring disease-associated motifs rather than an established pan-disease mechanism. The upstream mechanisms and evidence depth differ substantially by disease category. Oncogenic kinase-driven CLOCK post-translational modifications in HCC, phosphoproteomic remodeling in MAFLD, and epigenomic clock disruption persisting after HCV clearance represent findings that transcriptomics alone would not resolve. The near-complete absence of temporally resolved human tissue data remains the principal barrier to translational progress. This evidence gap limits the clinical actionability of current mechanistic findings across all disease categories. Circadian phase inference algorithms and prospective temporally designed cohort studies offer a methodologically grounded path toward clinically actionable circadian hepatology. Full article

The cardiovascular risk imposed by chronic kidney disease is significantly enhanced, and carotid atherosclerosis is an early indicator of systemic vascular damage. In this review, we summarize available data relative to primary prevention strategies for carotid atherosclerosis in chronic kidney disease (CKD) with a focus on risk-adapted and stage-specific management. We conducted a narrative review of the literature. A structured literature search was performed in major databases (PubMed, Scopus, Web of Science and Google Scholar), focusing on studies published between 2012 and 2025, including observational studies, randomized controlled trials, and international guideline recommendations. The review focuses on blood pressure management, lipid-lowering therapy, glycemic control, antiplatelet therapy, as well as lifestyle interventions and screening strategies in patients with CKD without a history of cerebrovascular events. CKD-specific processes, such as inflammation, endothelial dysfunction and vascular calcification, may influence the progression of carotid plaques, highlighting the need to improve traditional and non-traditional risk factor management. The focus of prevention continues to emphasize blood pressure (BP) and lipid control as well. At the same time, routine carotid screening and systematically implemented antiplatelet therapy have no known benefit, but the potential for elevated bleeding risk, especially in advanced CKD. Primary prevention should therefore focus on optimal medical treatment, as well as disease-specific strategies according to CKD stage. Additional CKD-specific studies with carotid endpoints are necessary. Full article

Background and Clinical Significance: Treatment options for chronic type B aortic dissections (TBADs) remain a topic of ongoing debate. Patients with post-dissection thoracoabdominal aortic aneurysms (PD-TAAAs) are typically younger than those with degenerative TAAAs, and their aortas undergo continuous remodeling over their lifetime. Fenestrated/branched endovascular aortic repair (F/B-EVAR) has shown promising results, but it can be challenged by the presence of a narrow true lumen, which hinders navigation and deployment of bridging components. Moreover, the presence of patent segmental arteries originating from the false lumen may prevent aneurysm shrinkage due to persistent flow, which may also result in insufficient spinal cord protection strategies and an increased risk of spinal cord ischemia. Consequently, multiple endovascular interventions are often necessary to address the persistent anatomical changes in these patients. Case Presentation: We present the case of a patient affected by a post-dissecting TAAA who underwent multiple open and endovascular treatment attempts. The presence of prior multiple laparotomies discouraged a new open surgical repair, while the hypertrophic segmental arteries and the presence of a narrow true lumen made standard F/B-EVAR unfeasible. The patient was successfully treated using a combination of different adjunctive advanced endovascular techniques, including minimally invasive segmental artery coil embolization (MiSACE) as a spinal cord preconditioning strategy and prevention of type II endoleak. Moreover, transcatheter electrosurgical septotomy (TES) was used to create a single aortic channel in the presence of a narrow true lumen, which allowed the deployment of a multifeatured, custom-made branched endograft. Conclusions: Endovascular repair of post-dissection TAAAs requires a thorough understanding of advanced endovascular adjuncts, which are often combined to overcome the complex anatomical challenges inherent to this disease. Although encouraging results have been reported, both segmental artery embolization for the indications described here and TES warrant further evaluation in prospective multicenter studies to confirm their safety and efficacy. Full article

Crohn’s disease (CD) is a chronic immune-mediated inflammatory disorder characterized by transmural inflammation and a progressive course that frequently leads to structural complications such as intestinal fibrosis. Fibrostenosing disease represents a major clinical challenge, affecting up to 50% of patients over time and often requiring surgical intervention. Despite advances in anti-inflammatory therapies, no effective treatments currently exist to prevent or reverse established fibrosis. Intestinal fibrosis arises from a dysregulated tissue remodeling process driven by excessive extracellular matrix deposition and persistent activation of mesenchymal cells, particularly fibroblasts and myofibroblasts. This process is orchestrated through complex interactions between immune and non-immune cells and mediated by key signaling pathways, including transforming growth factor beta (TGF-β1) and the TL1A/DR3 axis. Genetic susceptibility, notably variants in NOD2 and other fibrosis-related genes, contributes not only to disease risk but also to phenotype progression. Epigenetic mechanisms, particularly microRNAs such as the miR-29 and miR-200 families, further modulate fibrogenesis and represent promising non-invasive biomarkers. Additionally, intestinal dysbiosis and specific microbial signatures, including reduced short-chain fatty acid-producing bacteria and the presence of adherent-invasive Escherichia coli, play a critical role in promoting fibrotic pathways. Mesenteric adipose tissue, especially creeping fat, also contributes to fibrosis through immune and metabolic signaling. Emerging biomarkers related to collagen metabolism and advances in molecular profiling are improving early detection strategies. Novel therapeutic approaches targeting fibrogenic pathways, including anti-TL1A agents, show promising preliminary results. A deeper understanding of these mechanisms is essential to develop effective antifibrotic therapies and improve long-term outcomes in CD. Full article

Why do pandemics keep emerging despite decades of surveillance and response? Paleopathology, the study of disease traces in ancient remains, has been revolutionized by ancient DNA (aDNA) analysis and next-generation sequencing (NGS). Reconstructing pathogen genomes from archaeological material enables the identification of extinct lineages, the refinement of disease chronologies, and the characterization of long-term host-pathogen co-evolution. This provides context for public health challenges, including the emergence of pandemics and antimicrobial resistance (AMR). Infectious diseases are increasingly understood as complex phenomena arising from biological, ecological, and sociopolitical forces. Integrating paleopathology, aDNA, and paleomicrobiology supports a deep-time syndemic framework, revealing how recurring biosocial drivers have structured infectious disease risk throughout history. Ancient resistome studies demonstrate that AMR predates modern antibiotic use, reframing resistance as an intrinsic ecological feature rather than solely a modern phenomenon. Coronavirus disease 2019 (COVID-19) reaffirmed how infection intersects with chronic disease, health system fragility, and social inequities. This review highlights how integrating evolutionary perspectives into One Health shifts surveillance from a reactive approach to upstream risk mitigation and spillover prevention. Full article

Introduction: Cardiovascular diseases (CVDs) are a vast and widespread problem around the world, responsible for around one third of global deaths, of which 85% were due to heart attack and stroke in 2022. There are a lot of well-established risk factors for CVDs, including smoking, diabetes mellitus, obesity, poor diet, alcohol use, and sedentary lifestyle. Psychiatric disorders, however, are not among those frequently cited. Over a billion people worldwide suffer from some kind of mental disorder, with anxiety and depression being among the leading causes of long-term disability. All-cause death is significantly elevated in individuals with all mental health disorders. Methods: This narrative review aims to provide details on the selected psychiatric disorders and their pharmacotherapy with regard to the risk of developing cardiac illness by reviewing the available literature and the 2025 ESC Clinical Consensus Statement on mental health and cardiovascular disease. Results: Primary and secondary prevention of cardiovascular complications in the psychiatric disease population is an essential component in clinical healthcare. Conclusions: Taking all into account, it is essential to underline the role of the activation of the sympathetic nervous system and chronic inflammation, ultimately leading to metabolic syndrome in individuals with mental disorders, as well as an increase in residual cardiovascular risk and the development of CVDs, thereby worsening their long-term prognosis. In view of risky lifestyle behaviors in this population, it is essential to screen proactively, mitigate risk factors, consider the role of pharmacotherapy, and, if needed, initiate appropriate treatment. Full article