Search Results (1,629)

The human gut microbiota is a complex ecosystem that influences host metabolism, immune function, and cardiovascular health. Dysbiosis, defined as an imbalance in microbial composition or function, has been linked to the development and progression of atherosclerosis. This connection is mediated by microbial metabolites that enter the systemic circulation and interact with vascular and immune pathways. Among these, trimethylamine N-oxide (TMAO) has been most extensively studied and is consistently associated with cardiovascular events. Other metabolites, including lipopolysaccharides (LPS), short-chain fatty acids (SCFAs), and secondary bile acids, also contribute by modulating inflammation, endothelial function, and lipid metabolism. Recent research has expanded to emerging metabolites such as indoxyl sulfate, indole-3-propionic acid, and polyamines, which may provide additional mechanistic insights. These microbial products are increasingly explored as biomarkers of cardiovascular risk. TMAO has shown predictive value in large human cohorts, while microbiota composition and diversity measures remain less consistent across studies. However, interpretation of these biomarkers is limited by methodological variability, interindividual differences, and lack of standardization. Therapeutic interventions targeting the gut–heart axis are under investigation. Dietary strategies such as the Mediterranean diet and fiber-rich nutrition, probiotics and prebiotics, and fecal microbiota transplantation (FMT) show promise, while pharmacological approaches targeting TMAO or bile acid pathways are in early stages. This review summarizes current knowledge on the mechanistic, diagnostic, and therapeutic links between the gut microbiota and atherosclerosis, highlighting both established findings and emerging directions for future research. Full article

Longleaf pine forests are economically important habitats that stabilize and enrich the soil and store carbon over long periods. When mixed with oaks, these forests provide an abundance of lichen habitats. The tree canopy lichens promote greater moisture capture and retention and encourage canopy insects. Ground lichens limit some vascular plant germination and growth, promoting a more open and healthy pine community. There is a longstanding mutualistic relationship between longleaf pine habitat and lichens. Longleaf pine habitat has a long history of natural summer burning, which promotes a diverse understory and limits tree densities. Lichen diversity exceeds vascular plant diversity in many mature longleaf pine habitats, yet information on the impacts of prescribed fire on lichen species in these habitats is limited. We assessed lichen diversity and abundance before and after a prescribed ground fire in a longleaf pine/wiregrass habitat near Ocala, Florida. Pre-burn, we found greater lichen abundance and diversity on hardwoods, primarily oak species, than on pines. Post-burn, lichen abundance on hardwoods dropped overall by 28%. Lichen abundance on conifers dropped overall by 94%. Ground lichen species were basically eliminated, with a 99.5% loss. Our study provides insights into retaining lichen diversity after a prescribed burn. Hardwood trees, whether alive or standing dead, help retain lichen biodiversity after burning, whereas conifer trees do not support as many species. Landscapes may need to be actively managed by raking pine needle litter away from ground lichen beds, moistening the ground, or removing some lichen material before the burn and returning it to the site post-fire. Based on these results, we suggest retaining some oaks and conducting burns in a mosaic pattern that retains unburned areas. This will allow for lichens to recover between burns, significantly enhancing biodiversity and the ecological health of these longleaf pine communities. Full article

The rising prevalence of CKD, particularly within aging populations, demands effective and accessible self-management strategies. Three middle-aged and older adult inpatients (one female, two males; mean age 58.6 years ± 23) with CKD and preserved cognitive capacity (Mini-Mental State Examination) participated. A multiple case study was conducted in a Portuguese nephrology unit between November 2024 and February 2025, utilizing baseline assessments that included the Braden, Barthel, and Morse scales, as well as the KDQOL-SF. A targeted educational program addressed key CKD management aspects: disease understanding, vascular access care, medication regimens, and dietary restrictions. Pre- and post-intervention assessments measured knowledge gains. Results indicated improvements in participants’ knowledge and self-management capabilities across several domains. These included enhanced understanding of the disease process, vascular access for hemodialysis, dietary requirements, and fluid restrictions. Participants also demonstrated improved self-assessment of support systems, coping mechanisms, and family involvement. A 15% average increase in knowledge scores post-intervention was observed. This study provides preliminary evidence supporting the efficacy of a structured educational nursing program in improving CKD self-management. The significant improvements in knowledge and self-reported confidence suggest that targeted education is a valuable component of comprehensive CKD care. Future research should incorporate larger, more diverse samples and explore the long-term impact of the intervention. Furthermore, the integration of technological tools, such as personalized learning platforms and digital health, holds a significant promise for enhancing the accessibility and effectiveness of such educational programs. Full article

Background: Serum cystatin C is a promising biomarker for vascular risk, yet its nonlinear dose–response relationships and prognostic value in general populations remain unclear, particularly for stroke-specific outcomes. Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted in 1999–2002 cycles. A total of 11,610 participants were included in the primary analysis examining the cross-sectional association between cystatin C and stroke morbidity, using multivariate logistic regression models and odds ratios (ORs). Analyses utilized complete-case data (n = 11,610 for morbidity; n = 11,598 for mortality). Subsequently, 11,598 adults were retained for mortality endpoint analyses, which focused on the longitudinal association between cystatin C and stroke mortality, using cause-specific weighted multivariable Cox models and ratios (HRs). Restricted cubic splines identified nonlinear thresholds, and piecewise regression quantified risk gradients. Models were adjusted for sociodemographic/clinical/behavioral confounders. Results: Serum cystatin C exhibited a nonlinear dose–response relationship with stroke morbidity (p for nonlinear < 0.001), with an inflection point at 1.24 mg/L; below this threshold, each 0.1 mg/L increase conferred 13.84-fold higher odds (95% CI: 7.11–27.03, p < 0.001). For mortality, nonlinear thresholds were identified at 1.24 mg/L for all-cause/cause-specific mortality (HR = 6.73–10.60 per 0.1 mg/L increase, p < 0.001) and 1.81 mg/L for stroke-specific mortality. Conversely, cerebrovascular mortality demonstrated a linear association (HR = 1.43 per 1 mg/L increase, p = 0.008), though cystatin C independently predicted risk (HR = 1.38/continuous, p = 0.034 in fully adjusted models). Conclusions: This study identifies serum cystatin C as an independent predictor after full adjustment of stroke morbidity and all-cause and cardio-cerebrovascular mortality. Consequently, cystatin C emerges as a dual-purpose biomarker for early vascular injury detection in subclinical populations and integrated mortality risk stratification. Future research should validate these thresholds in prospective neuroimaging-confirmed cohorts and investigate interventions targeting cystatin C pathways to optimize preventive strategies. Full article

Atherosclerosis is now recognized as a chronic inflammatory disease of the arterial wall, in which perivascular adipose tissue (PVAT) has evolved from a passive structural component to a key player in regulating vascular homeostasis and the pathophysiology of atherosclerosis, playing an active, not just structural, role. PVAT surrounds blood vessels and influences them metabolically, immunologically, and vascularly by secreting adipokines, cytokines, and other bioactive mediators. Under physiological conditions, PVAT has protective roles, as it produces adiponectin, nitric oxide (NO), and other vasodilatory factors that help maintain vascular tone and reduce inflammation. In particular, brown-like PVAT (rich in Uncoupling Protein-1 (UCP1) and mitochondria) offers significant vasoprotective effects. Under pathological conditions (obesity, dyslipidemia, insulin resistance), PVAT undergoes a phenotypic transition towards a pro-inflammatory profile by increasing leptin, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) secretion and decreasing adiponectin, contributing to endothelial dysfunction, vascular smooth muscle cell (VSMC) proliferation, local immune cell recruitment, extracellular matrix (ECM) remodeling, and fibrosis. PVAT plays a complex role in vascular health and disease, interacting with systemic metabolism through the secretion of bioactive molecules. Metabolic imbalances can promote PVAT inflammation. Epigenetic alterations and micro ribonucleic acid (miRNAs) can influence PVAT inflammation, and modern imaging methods for PVAT assessment, such as the fat attenuation index (FAI) and artificial intelligence-assisted radiomic profiling, may become predictive biomarkers of cardiac risk. Future directions aim to identify biomarkers and develop targeted therapies that modulate PVAT inflammation and dysfunction in the context of cardiovascular diseases. Full article

Gene therapies that induce the body to produce therapeutic anti-vascular endothelial growth factor (anti-VEGF) proteins are an emerging topic related to neovascular age-related macular degeneration (nAMD). Continuous delivery of anti-VEGF protein directly to the target tissue offers the possibility of lifelong efficacy without the need for repeated and frequent eye injections. This novel approach could revolutionize patient management through optimizing clinical outcomes while simplifying service delivery. However, such gene therapies are anticipated to face unique challenges related to patients’ access and health technology assessment (HTA), and their integration into real-world eyecare practices. This article presents key elements raised at the European Access Academy (EAA) Fall convention (held in Rome in October 2024) regarding anticipated HTA challenges for gene therapies in nAMD. The important role of HTA and policymakers in ensuring that emerging gene therapies are accessible to all eligible patients is also highlighted. This article mainly focuses on the need for a fit-for-purpose EU HTA framework to address the widely varying utilization of standard of care in nAMD clinical practice, and to incorporate considerations about the long-term durability of gene therapies in nAMD. The importance of integrating real-world evidence (RWE) into the EU HTA framework is also discussed. Full article

The retinal vasculature provides a unique and non-invasive window into the health of the circulatory system. Josef Flammer, a pioneer in ocular vascular research, was the first to systematically describe how the state of retinal blood vessels reflects broader cardiovascular health. Because the retina is the only part of the human body where blood vessels can be visualized non-invasively, it serves as a valuable proxy for understanding microvascular conditions elsewhere, including the heart, brain, and lymphatics. Recent work has shown that retinal vasculature can be used as a proxy for microcirculatory dysfunction in other body systems, and that treatment using medical doses of vitamins can restore microcirculation, easing symptoms in disorders as diverse as glaucoma, AMD, and lymphedema without the need of pharmacological agents. The advent of machine learning tools to read retinal images promises both early detection of conditions and simplified monitoring of treatment progression. Full article

Hypertension in adolescence causes early vascular injury manifesting as endothelial dysfunction (ED), which signifies elevated cardiovascular risk. This review synthesizes recent insights (2020–2025) into ED’s mechanisms and detection in hypertensive youth. We highlight how reduced nitric oxide bioavailability, oxidative stress, inflammation, and hormonal changes in puberty contribute to ED and consequent vascular remodeling. Non-invasive diagnostic tools (e.g., flow-mediated dilation, peripheral arterial tonometry) reveal that even asymptomatic hypertensive adolescents have measurable ED linked to arterial stiffness and cardiac changes. Encouragingly, ED in youth appears reversible: exercise and dietary interventions improve endothelial function, and pharmacotherapy (ACE inhibitors, ARBs) can restore endothelial health beyond blood pressure control. Early identification of ED in hypertensive adolescents is therefore critical—it not only refines risk stratification (e.g., unmasking high-risk “white-coat” hypertension) but also presents an opportunity to initiate lifestyle modifications and therapy to preserve vascular function. Full article

Preeclampsia (PE) is not merely a pregnancy complication but a clinical manifestation of underlying vascular dysfunction with long-term health implications. It is diagnosed after 20 weeks of gestation as new-onset hypertension with proteinuria or organ involvement. The condition arises from impaired placental development, particularly defective spiral artery remodeling, which leads to placental ischemia and the release of antiangiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng). These circulating factors contribute to systemic endothelial dysfunction, resulting in hypertension, inflammation, and multiorgan stress. Histopathological findings, including acute atherosis and abnormal vascular remodeling, further reflect the cardiovascular damage underlying PE. This review synthesizes emerging evidence on the vascular and histological mechanisms of PE, highlighting novel biomarkers such as microRNAs and neprilysin, and the potential of advanced diagnostic tools, including machine learning. Importantly, PE is now recognized not only as an obstetric disorder but also as an early marker of future cardiovascular disease. This paradigm shift emphasizes the need for personalized prevention strategies, close surveillance of high-risk women, and long-term cardiovascular follow-up. Pregnancy thus represents a critical window for early detection and intervention in women’s cardiovascular health. Full article

Hepatocellular carcinoma (HCC) remains a global health challenge due to molecular heterogeneity and frequent delayed diagnosis. This comprehensive review synthesizes recent immunohistochemistry (IHC) advancements for HCC diagnosis, prognostication, and therapeutic prediction. We systematically evaluate conventional markers, such as hepatocyte paraffin 1 (HepPar1), arginase-1 (Arg-1), and glypican-3 (GPC3), as well as emerging biomarkers, detailing their diagnostic sensitivities and specificities in HCC with varied tumor differentiation. Prognostic immunostaining markers, such as Ki-67 proliferation index and vascular endothelial growth factor (VEGF) overexpression, correlate with reduced 5-year survival, while novel immune checkpoint IHC markers (PD-L1 and CTLA-4) predict response to immunotherapy, particularly in advanced HCC. This work provides evidence-based recommendations for optimizing IHC utilization in clinical practice while identifying knowledge gaps in biomarker validation and standardization. Full article

Background: Adhesive small bowel obstruction (ASBO) is a common and challenging surgical condition. In the absence of peritonitis, bowel ischemia, or clear surgical indicators on CT imaging, the initial management is typically non-operative. While clinical and radiological factors influencing non-operative management (NOM) are well described, the role of age and chronic health conditions remains less well defined. The primary aim of this study was to evaluate the incidence of NOM failure in patients with various comorbidities. Methods: This study utilized data from the National Inpatient Sample to analyze cases of ASBO between 2016 and 2019. Collected data included demographics, diagnosis, presence of chronic health conditions (diabetes mellitus, congestive heart failure, chronic kidney disease, chronic pulmonary diseases, peripheral vascular disease), length of hospital stay, and mortality. Patients were divided into two groups: Group A (18–65 years) and Group B (>65 years). We compared demographics comorbidities, NOM failure rates, and mortality between the groups. Univariate analysis was performed to assess age and comorbidities and risk factors for NOM failure in each group, followed by multivariable analysis within each group. Results: A total of 1,611,099 admissions with ASBO were identified in the NIS database; 63.03% were females. The failure rate of NOM in patients without comorbidities was 21%, compared to 26.5% in patients with one or more comorbidities. In Group A, 20% of patients required surgery, compared to 26.2% of patients in Group B (p = 0.001). Conclusions: Being aged over 65 and the presence of chronic health disease, excluding diabetes mellitus, are independent predictors of NOM failure in patients with ASBO. The presence of multiple comorbidities further increases the risk of NOM failure. Full article

Substance use during pregnancy is an increasingly important yet under-recognized threat to maternal and child health. This narrative review synthesizes the current evidence available on the epidemiology, pathophysiology, clinical management, and policy landscape of prenatal exposure to alcohol, tobacco, opioids, benzodiazepines, cocaine, cannabis, methamphetamines, and other synthetic drugs. All major psychoactive substances readily cross the placenta and can remain detectable in breast milk, leading to a shared cascade of obstetric complications (hypertensive disorders, placental abruption, pre-term labor), fetal consequences (growth restriction, structural malformations), and neonatal morbidities such as neonatal abstinence syndrome and sudden infant death. Mechanistically, trans-placental diffusion, oxidative stress, inflammatory signaling, and placental vascular dysfunction converge to disrupt critical neuro- and cardiovascular developmental windows. Early identification hinges on the combined use of validated screening questionnaires (4 P’s Plus, CRAFFT, T-ACE, AUDIT-C, TWEAK) and matrix-specific biomarkers (PEth, EtG, FAEE, CDT), while effective treatment requires integrated obstetric, addiction, and mental health services. Medication for opioid use disorders, particularly buprenorphine, alone or with naloxone, confers superior neonatal outcomes compared to methadone and underscores the value of harm-reducing non-punitive care models. Public-health strategies, such as Mexico’s “first 1 000 days” framework, wrap-around clinics, and home-visiting programs, demonstrate the potential of multisectoral interventions, but are hampered by structural inequities and punitive legislation that deter care-seeking. Research gaps persist in polysubstance exposure, culturally tailored therapies, and long-term neurodevelopmental trajectories. Multigenerational, omics-enabled cohorts, and digital longitudinal-care platforms represent promising avenues for closing these gaps and informing truly preventive perinatal health policies. Full article

Background/Objectives: Toxoplasma gondii, an obligate intracellular parasite, poses a major global health concern owing to its potential for congenital transmission, particularly during pregnancy. Current pharmacological treatments, including spiramycin and pyrimethamine, exhibit limitations in both efficacy and safety, underscoring the need for novel therapeutic strategies. In this study, we investigated the antiparasitic potential of BthTX-II, an Asp49 phospholipase A₂ (PLA₂) isolated from Bothrops jararacussu venom, in human trophoblast cells (BeWo) and third-trimester human placental explants infected with T. gondii. Methods: In vitro assays were performed using BeWo cells infected with T. gondii tachyzoites and treated with non-cytotoxic concentrations of BthTX-II (3.125, 1.56, and 0.78 µg/mL). An ex vivo model employing third-trimester human placental villous explants was used under similar conditions. Parasite proliferation, adhesion, and invasion were assessed alongside host immune response modulation. Results: Our findings demonstrate that BthTX-II reduces T. gondii proliferation in BeWo cells at all tested non-cytotoxic concentrations. The toxin also significantly impaired parasite adhesion and invasion while modulating host immune response by upregulating interleukin (IL)-6, IL-8, and macrophage migration inhibitory factor (MIF), and downregulating vascular endothelial growth factor—potentially disrupting parasite proliferation. In placental villous explants, BthTX-II (1.56 μg/mL) reduced T. gondii proliferation and modulated IL-8, MIF, and tumour necrosis factor-alpha levels without compromising tissue viability. Conclusions: These findings highlight BthTX-II as a potential candidate in toxoplasmosis treatment. Further investigation should focus on its dual role in limiting parasite development and modulating immune responses at the maternal–fetal interface. Full article

Background: Dicarbonyls and advanced glycation end-products (AGEs) contribute to oxidative stress, inflammation, and complications in type 2 diabetes mellitus (T2DM). Menaquinone-7 (MK-7), a vitamin K2 subtype, has shown benefits for glucose tolerance and vascular health in some studies. We evaluated the impact of MK-7 on dicarbonyls, free AGEs, and protein nitration/oxidation adducts in a rat model of T2DM. Methods: Male heterozygous (fa/+, control) and homozygous (fa/fa, diabetic) Zucker Diabetic Fatty rats were fed a diabetogenic diet without or with MK-7 for 12 weeks. After sacrifice, plasma dicarbonyls as well as plasma and urinary levels of free AGEs and protein nitration/oxidation adducts were quantified by isotope dilution tandem mass spectrometry. Results: Diabetic rats showed significantly increased plasma glyoxal, 3-deoxyglucosone, and fructosyl-lysine with non-significant trends toward increased methylglyoxal-derived hydroimidazolone and methionine sulfoxide, as well as reductions in methylglyoxal and dityrosine. Urinary carboxyethyl-lysine, carboxymethyl-lysine, fructosyl-lysine (all significant), and dityrosine (non-significant) were elevated in diabetic rats; glucosepane (non-significant) was reduced. MK-7 supplementation reduced no measured parameter but was associated with non-significant further increases in plasma glyoxal-derived hydroimidazolone, carboxyethyl-lysine, carboxymethyl-lysine, fructosyl-lysine, 3-nitrotyrosine, and methionine sulfoxide, as well as in urinary glyoxal-derived hydroimidazolone, carboxyethyl-lysine, fructosyl-lysine, and 3-nitrotyrosine, in diabetic rats. Correlation analysis revealed significant associations between glucose, dicarbonyls, AGEs, and oxidative markers. Conclusions: High-dose MK-7 supplementation did not improve dicarbonyl stress, AGE burden, or protein nitration/oxidation. With respect to available scientific evidence and our observations, the combination of glycemia-driven amplification of glycation and oxidative stress, as well as MK-7-induced glutathione depletion, were likely causative. Full article

This narrative review examines the complex relationship between sleep changes during the menopausal transition and cardiometabolic risks. The most common complaint about sleep is increased awakenings during sleep. Other complaints include having trouble falling asleep, waking up too early, insufficient and non-restorative sleep, and overall poor quality. Sleep determined using objective methods also indicates that greater awakenings after sleep onset are associated with the period of menopausal transition. Polysomnography recordings suggest physiological hyperarousal during sleep. Changes in other sleep metrics, such as sleep latency and sleep duration, are less consistent, and some studies suggest they may not worsen during the menopausal transition. These sleep issues are influenced by multiple factors, such as hormonal fluctuations, vasomotor symptoms, and psychosocial factors, and evidence suggests that hypothalamic kisspeptin/neurokinin B/dynorphin (KNDy) neurons are key underlying mechanisms for these associations. The menopausal transition is also associated with increases in cardiometabolic risk factors, such as body fat, altered lipid profiles, blood pressure, and vascular health. Emerging evidence suggests that poor sleep health during this period is associated with increased cardiometabolic risks and adverse cardiovascular outcomes. Thus, addressing sleep disturbances is crucial for comprehensive healthcare during the menopausal transition to safeguard long-term cardiometabolic health. Future research is needed to investigate interventions that can improve sleep and their impact on cardiometabolic health in this population experiencing increases in cardiometabolic risk. Full article