Search Results (932)

Plaque erosion (PE) is now recognized as a common and clinically significant cause of acute coronary syndromes (ACSs), accounting for up to 40% of cases. Unlike plaque rupture (PR), PE involves superficial endothelial loss over an intact fibrous cap and occurs in a low-inflammatory setting, typically affecting younger patients, women, and smokers with fewer traditional risk factors. The growing recognition of PE has been driven by high-resolution intracoronary imaging, particularly optical coherence tomography (OCT), which enables in vivo differentiation from PR. Identifying PE with OCT has opened the door to personalized treatment strategies, as explored in recent trials evaluating the safety of deferring stent implantation in selected cases in favor of intensive medical therapy. Given its unexpectedly high prevalence, PE is now recognized as a common pathophysiological mechanism in ACS, rather than a rare exception. This growing awareness underscores the importance of its accurate identification through OCT in clinical practice. Early recognition and a deeper understanding of PE are essential steps toward the implementation of precision medicine, allowing clinicians to move beyond “one-size-fits-all” models toward “mechanism-based” therapeutic strategies. This narrative review aims to offer an integrated overview of PE, tracing its epidemiology, elucidating the molecular and pathophysiological mechanisms involved, outlining its clinical presentations, and placing particular emphasis on diagnostic strategies with OCT, while also discussing emerging therapeutic approaches and future directions for personalized cardiovascular care. Full article

The transgenic animals have been yielding invaluable insights into amyloid pathology by replicating the key features of Alzheimer’s disease (AD). However, there is no clear relationship between senile plaques and memory deficits. Instead, cognitive impairment and synaptic dysfunction are particularly linked to a rise in Aβ_1-42 oligomer level. Thus, injection of Aβ_1-42 oligomers into a specific brain region is considered an alternative approach to investigate the effects of increased soluble Aβ species without any plaques, offering higher controllability, credibility and validity compared to the transgenic model. The hippocampal CA1 (cornu ammonis 1) region is selectively affected in the early stage of AD and specific targeting of CA1 region directly links Aβ oligomer-related pathology with memory impairment in early AD. Next, the inhibitory avoidance (IA) task, a learning paradigm to assess the synaptic basis of CA1-dependent contextual learning, triggers training-dependent synaptic plasticity similar to in vitro HFS (high-frequency stimulation). Given its reliability in assessing contextual memory and synaptic plasticity, this task provides an effective framework for studying early stage AD-related memory deficit. Therefore, in this review, we will focus on why Aβ_1-42 oligomer injection is a valid in vivo model to investigate the early stage of AD and why dorsal CA1 region serves as a target area to understand the adverse effects of Aβ_1-42 oligomers on contextual learning through the IA task. Full article

Background: Bimekizumab, secukinumab, and ixekizumab are IL-17-targeting biologics approved for the treatment of moderate-to-severe plaque psoriasis. While secukinumab and ixekizumab selectively inhibit IL-17A, bimekizumab targets both IL-17A and IL-17F, potentially providing greater anti-inflammatory efficacy. This study aimed to compare the real-world effectiveness, safety, and tolerability of these agents in a Polish dermatology center between 2019 and 2024. Methods: We conducted a retrospective analysis of 98 patients meeting at least one of the following criteria: PASI ≥ 10, BSA ≥ 10, DLQI ≥ 10, or involvement of special areas with inadequate response or contraindications to ≥2 systemic therapies. Patients with prior exposure only to IL-17 inhibitors were excluded. PASI, BSA, and DLQI scores were recorded at baseline, week 4, and week 12. Due to differences in dosing schedules, outcomes were aligned using standardized timepoints and exponential modeling of continuous response trajectories. Mixed-effects ANOVA was used to assess the influence of baseline factors (age, BMI, PsA status) on treatment outcomes. Adverse events were documented at each monthly follow-up visit. Results: Bimekizumab showed the greatest effect size for PASI reduction (Hedges’ g = 3.662), followed by secukinumab (2.813) and ixekizumab (1.986). Exponential modeling revealed a steeper response trajectory with bimekizumab (intercept = 0.289), suggesting a more rapid PASI improvement. The efficacy of bimekizumab was particularly notable in patients who were previously treated with IL-23 inhibitors. All three agents demonstrated favorable safety profiles, with no serious adverse events or discontinuations. The most frequent adverse events were mild and included upper respiratory tract infections and oral candidiasis. Conclusions: This real-world analysis confirmed that IL-17 inhibitors effectively improved PASI, BSA, and DLQI scores in moderate-to-severe psoriasis. Bimekizumab demonstrated the most rapid early improvements and a higher modeled likelihood of complete clearance, without significant differences at week 12. All agents were well tolerated, underscoring the need for further individualized, large-scale studies. Full article

Background/Objectives: Educational background is an aspect of socio-economic status, that may be associated with higher caries risk. This study aimed to investigate differences in caries prevalence between different school types for older adolescents in Greifswald, Germany. Methods: Cross-sectional data were collected as part of compulsory dental school examinations between 2020 and 2023. Oral health status was assessed according to WHO criteria by six calibrated examiners and reported as mean D₃MFT (D₃: dentin caries, M: missing, F: filled, SD/±: standard deviation). To compare educational backgrounds, the adolescents were divided into two groups according to their age and type of school (11–15 and 16–18 years old). Results: The study included 5816 adolescents (48.7% females) with a mean D₃MFT of 0.65 (Q1–Q3: 0–1); 73.8% were clinically caries-free, having D₃MFT = 0, confirming the polarization in caries experience with 2.5 ± 2.13 SaC index. The logistic regression model showed a significantly increased Odds Ratio for having caries in relation to age, being male, having plaque or gingivitis (p < 0.005). There were significant differences in caries experience and prevalence between school types, where high schools had the lowest D₃MFT values in both age groups (0.39 ± 1.17 and 0.64 ± 1.49, respectively). The highest D₃MFT values were in schools for special educational needs in younger adolescents (1.12 ± 1.9) and in vocational schools in older adolescents (1.63 ± 2.55). Conclusions: In a low-caries-risk population, there were significant differences in caries experience and prevalence among adolescents in different school types. Prevention strategies should aim to reduce the polarization in caries across different educational backgrounds in late adolescence. Full article

Neuroinflammation is a key feature of Alzheimer’s disease (AD), and stem cell therapies have emerged as promising candidates due to their immunomodulatory properties. Neuro-Cells (NC), a combination of unmodified mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs), have demonstrated therapeutic potential in models of central nervous system (CNS) injury and neurodegeneration. Here, we studied the effects of NC in APPswe/PS1dE9 mice, an AD mouse model. Twelve-month-old APPswe/PS1dE9 mice or their wild-type littermates were injected with NC or vehicle into the cisterna magna. Five to six weeks post-injection, cognitive, locomotor, and emotional behaviors were assessed. The brain was stained for amyloid plaque density using Congo red, and for astrogliosis using DAPI and GFAP staining. Gene expression of immune activation markers (Il-1β, Il-6, Cd45, Tnf) and plasticity markers (Tubβ3, Bace1, Trem2, Stat3) was examined in the prefrontal cortex. IL-6 secretion was measured in cultured human monocytes following endotoxin challenge and NC treatment. Untreated APPswe/PS1dE9 mice displayed impaired learning in the conditioned taste aversion test, reduced object exploration, and anxiety-like behavior, which were improved in the NC-treated mutants. NC treatment normalized the expression of several immune and plasticity markers and reduced the density of GFAP-positive cells in the hippocampus and thalamus. NC treatment decreased amyloid plaque density in the hippocampus and thalamus, targeting plaques of <100 μm². Additionally, NC treatment suppressed IL-6 secretion by human monocytes. Thus, NC treatment alleviated behavioral deficits and reduced amyloid plaque formation in APPswe/PS1dE9 mice, likely via anti-inflammatory mechanisms. The reduction in IL-6 production in human monocytes further supports the potential of NC therapy for the treatment of AD. Full article

Alzheimer’s disease (AD) involves the accumulation of amyloid-β (Aβ) plaques, whose quantification plays a central role in understanding disease progression. Automated segmentation of Aβ deposits in histopathological micrographs enables large-scale analyses but is hindered by the high cost of detailed pixel-level annotations. Weakly supervised learning offers a promising alternative by leveraging coarse or indirect labels to reduce the annotation burden. We evaluated a weakly supervised approach to segment and analyze thioflavin-S-positive parenchymal amyloid pathology in AD and age-matched brains. Our pipeline integrates three key components, each designed to operate under weak supervision. First, robust preprocessing (including retrospective multi-image illumination correction and gradient-based background estimation) was applied to enhance image fidelity and support training, as models rely more on image features. Second, class activation maps (CAMs), generated by a compact deep classifier SqueezeNet, were used to identify, and coarsely localize amyloid-rich parenchymal regions from patch-wise image labels, serving as spatial priors for subsequent refinement without requiring dense pixel-level annotations. Third, a patch-based convolutional neural network, U-Net, was trained on synthetic data generated from micrographs based on CAM-derived pseudo-labels via an extensive object-level augmentation strategy, enabling refined whole-image semantic segmentation and generalization across diverse spatial configurations. To ensure robustness and unbiased evaluation, we assessed the segmentation performance of the entire framework using patient-wise group k-fold cross-validation, explicitly modeling generalization across unseen individuals, critical in clinical scenarios. Despite relying on weak labels, the integrated pipeline achieved strong segmentation performance with an average Dice similarity coefficient (≈0.763) and Jaccard index (≈0.639), widely accepted metrics for assessing segmentation quality in medical image analysis. The resulting segmentations were also visually coherent, demonstrating that weakly supervised segmentation is a viable alternative in histopathology, where acquiring dense annotations is prohibitively labor-intensive and time-consuming. Subsequent morphometric analyses on automatically segmented Aβ deposits revealed size-, structural complexity-, and global geometry-related differences across brain regions and cognitive status. These findings confirm that deposit architecture exhibits region-specific patterns and reflects underlying neurodegenerative processes, thereby highlighting the biological relevance and practical applicability of the proposed image-processing pipeline for morphometric analysis. Full article

Coronary artery disease (CAD) constitutes a major contributor to morbidity, mortality and healthcare burden worldwide. Recent innovations in imaging modalities, pharmaceuticals and interventional techniques have revolutionized diagnostic and treatment options, necessitating the reevaluation of established drug protocols or the consideration of newer alternatives. The utilization of beta blockers (BBs) in the setting of acute myocardial infarction (AMI), shifting from the pre-reperfusion to the thrombolytic and finally the primary percutaneous coronary intervention (pPCI) era, has become increasingly more selective and contentious. Nonetheless, the extent of myocardial necrosis remains a key predictor of outcomes in this patient population, with large trials establishing the beneficial use of beta blockers. Computed tomography coronary angiography (CTCA) has emerged as a highly effective diagnostic tool for delineating the coronary anatomy and atheromatous plaque characteristics, with the added capability of MESH-3D model generation. Induction and preservation of a low heart rate (HR), regardless of the underlying sequence, is of critical importance for high-quality results. Landiolol is an intravenous beta blocker with an ultra-short duration of action (t1/2 = 4 min) and remarkable β1-receptor specificity (β1/β2 = 255) and pharmacokinetics that support its potential for systematic integration into clinical practice. It has been increasingly recognized for its importance in both acute (primarily studied in STEMI and, to a lesser extent, NSTEMI pPCI) and chronic (mainly studied in elective PCI) CAD settings. Given the limited literature focusing specifically on landiolol, the aim of this narrative review is to examine its pharmacological properties and evaluate its current and future role in enhancing both diagnostic imaging quality and therapeutic outcomes in patients with CAD. Full article

Carotid atherosclerotic stenosis (CAS) is a leading cause of ischemic stroke. Current understanding of plaque vulnerability remains largely confined to histopathological characterization. Consequently, identifying molecular determinants of plaque stability represents a major challenge to advance prevention strategies. Untargeted metabolomic analysis was performed using mass spectrometry coupled to liquid chromatography on carotid plaques removed from patients with CAS undergoing endarterectomy. To identify factors influencing plaque stability, we compared 42 asymptomatic with 30 symptomatic CAS patients. Associations between each annotated metabolite in plaques and asymptomatic CAS status were assessed using logistic regression models. Asymptomatic patients exhibited lower plasmatic levels of C-reactive protein (CRP) and higher HDL-cholesterol. Within the plaques, caffeine and its catabolites, paraxanthine and methylxanthine, were associated with plaque stability and were correlated with HDL-cholesterol. Additional plant-based diet biomarkers including N5-acetylornithine, gentisic acid, proline betaine, and homostachydrine were also associated with plaque stability. In contrast, N-methylpyridone carboxamides, reflecting niacin excess, involved in vascular inflammatory processes, were both associated with plaque vulnerability and also correlated with higher CRP. Our findings provide molecular evidence that plant-based diets, including coffee, promote carotid plaque stability, while excessive niacin intake, linked to processed foods, may be detrimental. Metabolomics offers new insights into food exposome-related vascular risk. Full article

Objectives: The mechanisms linking vitamin D deficiency to carotid artery stenosis (CAS) remain unclear. Data on cardiovascular outcomes in CAS patients with vitamin D deficiency are limited. We investigated the association of vitamin D deficiency with carotid plaque morphology and patient outcomes in high-grade CAS. Methods: A total of 332 patients undergoing carotid endarterectomy for symptomatic (n = 113, 34%) or asymptomatic (n = 219, 66%) CAS were included. Preoperative vitamin D levels were measured, and duplex sonography was used to assess luminal narrowing. Associations of vitamin D with clinical presentation were analyzed using univariate and multivariate linear regression. For vitamin D deficiency and the prediction of major adverse cardiovascular events (MACE) and all-cause mortality, the Cox proportional hazard regression model was used. Results: The median age was 69 years (interquartile range (IQR) 64–74), and 94 (29.3%) patients were female. Vitamin D deficiency was present in 84 (25%) patients. Symptomatic patients had significantly lower vitamin D levels (41.2 nmol/L, IQR 25.1–63.5) than asymptomatic patients (51.6 nmol/L, IQR 30.5–74.3, p = 0.011). Patients with echolucent (44.9 nmol/L, IQR 27.4–73.7) or mixed plaques (39.2 nmol/L, IQR 22.9–63.5) had lower vitamin D levels than those with echogenic plaques (52.3 nmol/L, IQR 34.1–75.7). Vitamin D deficiency predicted MACE and all-cause mortality with an adjusted HR of 1.6, 95% CI of 1.1–2.6, and p = 0.030 and an HR of 2.2, 95% CI of 1.3–3.6, and p = 0.002, respectively, in a multivariable Cox proportional hazard regression model. Conclusions: A deficiency in vitamin D was correlated with unstable plaque characteristics and symptomatic CAS. Furthermore, vitamin D deficiency was associated with long-term adverse cardiovascular outcomes and mortality, suggesting its potential as a modifiable risk factor for improved risk stratification in patients undergoing carotid endarterectomy. Full article

Background: While carotid pathologies are well-established risk factors for stroke, their specific effects on outcomes following stroke that cannot be classified as atherosclerotic remain unclear. In this study, we aimed to determine whether carotid pathologies are associated with functional dependence (FD) 3 months after small vessel occlusion (SVO) stroke. Methods: This retrospective study included patients with a first-ever SVO stroke admitted to a single cerebrovascular-specialty hospital between October 2021 and March 2024. Standardized ultrasound criteria were used to grade the carotid plaques. The modified Rankin scale (mRS) was used to assess functional outcomes at 3 months. Logistic regression analysis was performed to identify FD predictors (mRS of ≥2). Results: Of the 372 included patients, 276 achieved functional independence and 96 experienced FD at 3 months. Univariable analysis revealed an association between carotid plaque grade III and FD (odds ratio [OR], 2.46; 95% confidence interval [CI], 1.05–6.51; p = 0.049). However, this association was not significant in the multivariable model. Overall, age (adjusted OR, 1.07; 95% CI 1.03–1.10, p < 0.001), NIHSS at initial presentation (adjusted OR, 1.84; 95% CI, 1.55–2.18; p < 0.001), and diabetes (adjusted OR, 2.84; 95% CI, 1.37–5.92; p = 0.005) were independently associated with FD 3 months after SVO stroke. Conclusions: Carotid plaque severity was not independently associated with functional outcomes 3 months after SVO stroke. Age, NIHSS at initial presentation, and diabetes were identified as independent FD predictors. Future in-depth studies are warranted to confirm the complex interplay of factors influencing functional outcomes in patients with SVO stroke and carotid pathologies simultaneously. Full article

Coronary plaque vulnerability, more than luminal stenosis, drives acute coronary syndromes. Optical coherence tomography (OCT), intravascular ultrasound (IVUS), and coronary computed tomography angiography (CCTA) visualize plaque morphology in vivo, but manual interpretation is time-consuming and operator-dependent. We performed a narrative literature survey of artificial intelligence (AI) applications—focusing on machine learning (ML) architectures—for automated coronary plaque segmentation and risk characterization across OCT, IVUS, and CCTA. Recent ML models achieve expert-level lumen and plaque segmentation, reliably detecting features linked to vulnerability such as a lipid-rich necrotic core, calcification, positive remodelling, and a napkin-ring sign. Integrative radiomic and multimodal frameworks further improve prognostic stratification for major adverse cardiac events. Nonetheless, progress is constrained by small, single-centre datasets, heterogeneous validation metrics, and limited model interpretability. AI-enhanced plaque assessment offers rapid, reproducible, and comprehensive coronary imaging analysis. Future work should prioritize large multicentre repositories, explainable architectures, and prospective outcome-oriented validation to enable routine clinical adoption. Full article

Toscana virus (TOSV) and Schmallenberg virus (SBV) are arthropod-borne viruses from the Bunyaviricetes class, posing significant human and animal health threats. TOSV, endemic to the Mediterranean region, is a notable human pathogen detected in various animals, suggesting potential zoonotic reservoirs. SBV emerged in Europe in 2011, affecting ruminants and causing reproductive issues, with substantial economic implications. The rapid spread of both viruses underscores the need for novel antiviral strategies. Host defense peptides (HDPs), particularly those derived from scorpion venom, are gaining attention for their antiviral potential. This study investigated pantinin-1 and pantinin-2 for their inhibitory activity against TOSV and SBV by plaque reduction assay, tissue culture infective dose (TCID₅₀) determination, and the analysis of M gene expression via qPCR. Both peptides exhibited potent virucidal activity, with IC₅₀ values of approximately 10 µM, depending on the specific in vitro cell model used. Additionally, the selectivity index (SI) values were favorable across all virus/cell line combinations, with particularly optimal results observed for pantinin-2. In human U87-MG neuronal cells, both peptides effectively blocked TOSV infection, a critical finding given the virus’s association with neurological conditions like encephalitis. The strong efficacy of these peptides against these viruses underscores the broader applicability of venom-derived peptides as promising antiviral agents, particularly in the context of emerging viral pathogens and increasing resistance to conventional therapeutics. Further studies are needed to optimize their antiviral potency and to assess their safety in vivo using animal models. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by amyloid-β plaque accumulation, tau tangles, and extensive neuroinflammation. Neuroinflammation, driven by glial cells like microglia and astrocytes, plays a critical role in AD progression. Initially, these cells provide protective functions, such as debris clearance and neurotrophic support. However, as AD progresses, chronic activation of these cells exacerbates inflammation, contributing to synaptic dysfunction, neuronal loss, and cognitive decline. Microglia release pro-inflammatory cytokines and reactive oxygen species (ROS), while astrocytes undergo reactive astrogliosis, further impairing neuronal health. This maladaptive response from glial cells significantly accelerates disease pathology. Current AD treatments primarily aim at symptomatic relief, with limited success in disease modification. While amyloid-targeting therapies like Aducanumab and Lecanemab show some promise, their efficacy remains limited. In this context, natural compounds have gained attention for their potential to modulate neuroinflammation and promote neuroprotection. Among these, butyrate and lauric acid are particularly notable. Butyrate, produced by a healthy gut microbiome, acts as a histone deacetylase (HDAC) inhibitor, reducing pro-inflammatory cytokines and supporting neuronal health. Lauric acid, on the other hand, enhances mitochondrial function, reduces oxidative stress, and modulates inflammatory pathways, thereby supporting glial and neuronal health. Both compounds have been shown to decrease amyloid-β deposition, reduce neuroinflammation, and promote neuroprotection in AD models. This review explores the mechanisms through which butyrate and lauric acid modulate glial and neuronal activity, highlighting their potential as therapeutic agents for mitigating neuroinflammation and slowing AD progression. Full article

Fullerenes and fullerenols exhibit antioxidant and anti-inflammatory properties, making them promising candidates for Alzheimer’s disease (AD) therapy. Unlike conventional anti-inflammatory drugs, these compounds have multitargeted effects, including their ability to inhibit amyloid fibril formation. However, few studies have explored their efficacy in high-validity AD models. Female APPswe/PS1E9 (APP/PS1) mice and their wild-type (WT) littermates were orally administered with fullerene C₆₀ (0.1 mg/kg/day) or fullerenol C₆₀(OH)₂₄ (0.15 mg/kg/day) for 10 months starting at 2 months of age. Behavioral assessments were performed at 12 months of age. Amyloid plaque density and size were analyzed in the brain regions using Congo red staining. The expression of genes related to inflammation and plasticity was examined, and an in vitro assay was used to test the toxicity of fullerenol and its effect on amyloid β peptide 42 (Aβ42)-induced reactive oxygen species (ROS) production. Fullerenol reduced the maximum plaque size in the cortex and hippocampus, decreased the small plaque density in the hippocampus and thalamus, and prevented an increase in glial fibrillary acidic protein (GFAP) positive cell density in the mutants. Both treatments improved cognitive and emotional behaviors and reduced Il1β and increased Sirt1 expression. In vitro, fullerenol was non-toxic across a range of concentrations and reduced Aβ42-induced ROS production in brain endothelial cells and astrocytes. Long-term administration of fullerene or fullerenol improved behavioral and molecular markers of AD in APP/PS1 mice, with fullerenol showing additional benefits in reducing amyloid burden. Full article

Background and Objectives: Periodontitis is an inflammatory disease that compromises the supporting structures of the teeth, leading to irreversible tissue damage and tooth loss. While subgingival professional mechanical plaque removal (PMPR) remains the gold standard treatment, there is increasing interest in adjunctive therapies. Platelet-rich fibrin (PRF) has gained attention as a promising biomaterial to enhance periodontal healing and regeneration. This study aimed to evaluate the clinical and immunological effectiveness of PRF as an adjunct to PMPR. Materials and Methods: Clinical studies published between January 2019 and August 2024 were included from the ProQuest, PubMed, PMC, ScienceDirect, Scopus, and EBSCO databases. Seven studies met the inclusion criteria, focusing on adults with periodontitis treated with PRF + PMPR compared to PMPR alone. Primary outcomes included changes in clinical and immunological parameters. Risk of bias was assessed using the Cochrane ROB2 tool. Meta-analysis was conducted using both fixed-effect and random-effects models, depending on heterogeneity. Results: The meta-analysis demonstrated significant improvements in clinical outcomes in the PRF + PMPR group, with reductions in probing pocket depth (SMD: −1.43 mm; 95% CI: −2.05 to −0.81; p < 0.00001), clinical attachment level (SMD: −1.34 mm; 95% CI: −1.95 to −0.73; p < 0.0001), bleeding on probing (SMD: −0.75 mm; 95% CI: −1.11 to −0.39; p < 0.00001), gingival recession (SMD: −0.79 mm; 95% CI: −1.33 to −0.25; p = 0.004), and gingival index (SMD: −0.82 mm; 95% CI: −1.37 to −0.28; p = 0.003). Favorable trends were also observed in IL-10, TGF-β, VEGF, PDGF-BB, periostin, and type I collagen levels. Conclusions: PRF enhances clinical and immunological outcomes and supports periodontal tissue stability when used as an adjunct to non-surgical therapy. Full article