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Systemic amyloidosis involves the deposition of misfolded proteins in organs/tissues, leading to progressive organ dysfunction and failure. Congo red is the gold-standard chemical stain for visualizing amyloid deposits in tissue, showing birefringence under polarization microscopy. However, Congo red staining is tedious and costly to perform, and prone to false diagnoses due to variations in amyloid amount, staining quality and manual examination of tissue under a polarization microscope. We report virtual birefringence imaging and virtual Congo red staining of label-free human tissue to show that a single neural network can transform autofluorescence images of label-free tissue into brightfield and polarized microscopy images, matching their histochemically stained versions. Blind testing with quantitative metrics and pathologist evaluations on cardiac tissue showed that our virtually stained polarization and brightfield images highlight amyloid patterns in a consistent manner, mitigating challenges due to variations in chemical staining quality and manual imaging processes in the clinical workflow.

BACKGROUND: Increases in low-density lipoprotein cholesterol (LDL-C) can occur on carbohydrate restricted ketogenic diets. Lean metabolically healthy individuals with a low triglyceride-to-high-density lipoprotein cholesterol ratio appear particularly susceptible, giving rise to the novel lean mass hyper-responder (LMHR) phenotype. OBJECTIVES: The purpose of the study was to assess coronary plaque burden in LMHR and near-LMHR individuals with LDL-C ≥190 mg/dL (ketogenic diet [KETO]) compared to matched controls with lower LDL-C from the Miami Heart (MiHeart) cohort. METHODS: There were 80 KETO individuals with carbohydrate restriction-induced LDL-C ≥190 mg/dL, high-density lipoprotein cholesterol ≥60 mg/dL, and triglyceride levels ≤80 mg/dL, without familial hypercholesterolemia, matched 1:1 with MiHeart subjects for age, gender, race, hyperlipidemia, hypertension, and smoking status. Coronary artery calcium and coronary computed tomography angiography (CCTA) were used to compare coronary plaque between groups and correlate LDL-C to plaque levels. RESULTS: The matched mean age was 55.5 years, with a mean LDL-C of 272 (maximum LDL-C of 591) mg/dl and a mean 4.7-year duration on a KETO. There was no significant difference in coronary plaque burden in the KETO group as compared to MiHeart controls (mean LDL 123 mg/dL): coronary artery calcium score (median 0 [IQR: 0-56]) vs (1 [IQR: 0-49]) (P = 0.520) CCTA total plaque score (0 [IQR: 0-2] vs [IQR: 0-4]) (P = 0.357). There was also no correlation between LDL-C level and CCTA coronary plaque. CONCLUSIONS: Coronary plaque in metabolically healthy individuals with carbohydrate restriction-induced LDL-C ≥190 mg/dL on KETO for a mean of 4.7 years is not greater than a matched cohort with 149 mg/dL lower average LDL-C. There is no association between LDL-C and plaque burden in either cohort. (Diet-induced Elevations in LDL-C and Progression of Atherosclerosis [Keto-CTA]; NCT057333255).

Purpose To clarify the predominant causative plaque constituent for periprocedural myocardial injury (PMI) following percutaneous coronary intervention: (a) erythrocyte-derived materials, indicated by a high plaque-to-myocardium signal intensity ratio (PMR) at coronary atherosclerosis T1-weighted characterization (CATCH) MRI, or (b) lipids, represented by a high maximum 4-mm lipid core burden index (maxLCBI4 mm) at near-infrared spectroscopy intravascular US (NIRS-IVUS). Materials and Methods This retrospective study included consecutive patients who underwent CATCH MRI before elective NIRS-IVUS-guided percutaneous coronary intervention at two facilities. PMI was defined as post-percutaneous coronary intervention troponin T values greater than five times the upper reference limit. Multivariable analysis was performed to identify predictors of PMI. Finally, the predictive capabilities of MRI, NIRS-IVUS, and their combination were compared. Results A total of 103 lesions from 103 patients (median age, 72 years [IQR, 64-78]; 78 male patients) were included. PMI occurred in 36 lesions. In multivariable analysis, PMR emerged as the strongest predictor (P = .001), whereas maxLCBI4 mm was not a significant predictor (P = .07). When PMR was excluded from the analysis, maxLCBI4 mm emerged as the sole independent predictor (P = .02). The combination of MRI and NIRS-IVUS yielded the largest area under the receiver operating curve (0.86 [95% CI: 0.64, 0.83]), surpassing that of NIRS-IVUS alone (0.75 [95% CI: 0.64, 0.83]; P = .02) or MRI alone (0.80 [95% CI: 0.68, 0.88]; P = .30). Conclusion Erythrocyte-derived materials in plaques, represented by a high PMR at CATCH MRI, were strongly associated with PMI independent of lipids. MRI may play a crucial role in predicting PMI by offering unique pathologic insights into plaques, distinct from those provided by NIRS. Keywords: Coronary Plaque, Periprocedural Myocardial Injury, MRI, Near-Infrared Spectroscopy Intravascular US Supplemental material is available for this article. © RSNA, 2024.

The diagnostic value of imaging Aβ plaques in Alzheimer's disease (AD) has accelerated the development of fluorine-18 labeled radiotracers with a longer half-life for easier translation to clinical use. We have developed [18F]flotaza, which shows high binding to Aβ plaques in postmortem human AD brain slices with low white matter binding. We report the binding of [18F]flotaza in postmortem AD hippocampus compared to cognitively normal (CN) brains and the evaluation of [18F]flotaza in transgenic 5xFAD mice expressing Aβ plaques. [18F]Flotaza binding was assessed in well-characterized human postmortem brain tissue sections consisting of HP CA1-subiculum (HP CA1-SUB) regions in AD (n = 28; 13 male and 15 female) and CN subjects (n = 32; 16 male and 16 female). Adjacent slices were immunostained with anti-Aβ and analyzed using QuPath. In vitro and in vivo [18F]flotaza PET/CT studies were carried out in 5xFAD mice. Post-mortem human brain slices from all AD subjects were positively IHC stained with anti-Aβ. High [18F]flotaza binding was measured in the HP CA1-SUB grey matter (GM) regions compared to white matter (WM) of AD subjects with GM/WM > 100 in some subjects. The majority of CN subjects had no decipherable binding. Male AD exhibited greater WM than AD females (AD WM♂/WM♀ > 5; p < 0.001) but no difference amongst CN WM. In vitro studies in 5xFAD mice brain slices exhibited high binding [18F]flotaza ratios (>50 versus cerebellum) in the cortex, HP, and thalamus. In vivo, PET [18F]flotaza exhibited binding to Aβ plaques in 5xFAD mice with SUVR~1.4. [18F]Flotaza is a new Aβ plaque PET imaging agent that exhibited high binding to Aβ plaques in postmortem human AD. Along with the promising results in 5xFAD mice, the translation of [18F]flotaza to human PET studies may be worthwhile.

BackgroundVariants in ABCA7, a member of the ABC transporter superfamily, have been associated with increased risk for developing late onset Alzheimer's disease (LOAD).MethodsCRISPR-Cas9 was used to generate an Abca7V1613M variant in mice, modeling the homologous human ABCA7V1599M variant, and extensive characterization was performed.ResultsAbca7V1613M microglia show differential gene expression profiles upon lipopolysaccharide challenge and increased phagocytic capacity. Homozygous Abca7V1613M mice display elevated circulating cholesterol and altered brain lipid composition. When crossed with 5xFAD mice, homozygous Abca7V1613M mice display fewer Thioflavin S-positive plaques, decreased amyloid beta (Aβ) peptides, and altered amyloid precursor protein processing and trafficking. They also exhibit reduced Aβ-associated inflammation, gliosis, and neuronal damage.DiscussionOverall, homozygosity for the Abca7V1613M variant influences phagocytosis, response to inflammation, lipid metabolism, Aβ pathology, and neuronal damage in mice. This variant may confer a gain of function and offer a protective effect against Alzheimer's disease-related pathology.HighlightsABCA7 recognized as a top 10 risk gene for developing Alzheimer's disease. Loss of function mutations result in increased risk for LOAD. V1613M variant reduces amyloid beta plaque burden in 5xFAD mice. V1613M variant modulates APP processing and trafficking in 5xFAD mice. V1613M variant reduces amyloid beta-associated damage in 5xFAD mice.

Objectives: The prevalence and the economic burden of periodontal disease are high. To save or replace diseased teeth, an objective prognosis assessment using the long-term predictability of the various treatment options should be performed. As dental implants have become a treatment of choice for replacing missing teeth, the number of implant failures and complications has also increased. The objective of this review was to compare the cost-effectiveness of saving and maintaining the teeth vs replacing them with dental implants in patients with severe periodontal disease (with hopeless or questionable teeth). Method and materials: A database search was conducted using Medline (OVID), Embase, Web of Science, and CINAHL electronic sources until July 2023. Two reviewers reviewed the papers in accordance with the specific selection criteria after choosing the abstracts that met the initial selection criterion for full article retrieval. Results: Twelve articles were included, of which nine articles discussed the cost-effectiveness of preserving teeth in severe periodontal disease and three articles discussed the effectiveness of implants that replaced the periodontally compromised teeth. It was found that placing and maintaining implants was more costly than properly treating and maintaining periodontally compromised teeth. Supportive periodontal treatment contributed the most to the cost during the periodontal treatment. Conclusions: Implants are an effective choice to replace missing teeth; however, these are not permanent, present complications, and require strict maintenance. Thus, when deciding whether to maintain a periodontally compromised tooth or to replace it with a dental implant, in terms of cost-effectiveness, implant maintenance cost as well as the cost associated with treating implant complications should be considered. This cost seems to surpass the cost of treatment and maintenance of periodontally compromised teeth. [ABSTRACT FROM AUTHOR]

Clinical risk scores based on traditional risk factors of atherosclerosis correlate imprecisely to an individuals complex pathophysiological predisposition to atherosclerosis and provide limited accuracy for predicting major adverse cardiovascular events (MACE). Over the past two decades, computed tomography scanners and techniques for coronary computed tomography angiography (CCTA) analysis have substantially improved, enabling more precise atherosclerotic plaque quantification and characterization. The accuracy of CCTA for quantifying stenosis and atherosclerosis has been validated in numerous multicentre studies and has shown consistent incremental prognostic value for MACE over the clinical risk spectrum in different populations. Serial CCTA studies have advanced our understanding of vascular biology and atherosclerotic disease progression. The direct disease visualization of CCTA has the potential to be used synergistically with indirect markers of risk to significantly improve prevention of MACE, pending large-scale randomized evaluation.

BACKGROUND: In Alzheimers disease (AD), microglia surround extracellular plaques and mount a sustained inflammatory response, contributing to the pathogenesis of the disease. Identifying approaches to specifically target plaque-associated microglia (PAMs) without interfering in the homeostatic functions of non-plaque associated microglia would afford a powerful tool and potential therapeutic avenue. METHODS: Here, we demonstrated that a systemically administered nanomedicine, hydroxyl dendrimers (HDs), can cross the blood brain barrier and are preferentially taken up by PAMs in a mouse model of AD. As proof of principle, to demonstrate biological effects in PAM function, we treated the 5xFAD mouse model of amyloidosis for 4 weeks via systemic administration (ip, 2x weekly) of HDs conjugated to a colony stimulating factor-1 receptor (CSF1R) inhibitor (D-45113). RESULTS: Treatment resulted in significant reductions in amyloid-beta (Aβ) and a stark reduction in the number of microglia and microglia-plaque association in the subiculum and somatosensory cortex, as well as a downregulation in microglial, inflammatory, and synaptic gene expression compared to vehicle treated 5xFAD mice. CONCLUSIONS: This study demonstrates that systemic administration of a dendranib may be utilized to target and modulate PAMs.

IntroductionAlzheimer's disease (AD) is a neurodegenerative disorder with multifactorial etiology, including genetic factors that play a significant role in disease risk and resilience. However, the role of genetic diversity in preclinical AD studies has received limited attention.MethodsWe crossed five Collaborative Cross strains with 5xFAD C57BL/6J female mice to generate F1 mice with and without the 5xFAD transgene. Amyloid plaque pathology, microglial and astrocytic responses, neurofilament light chain levels, and gene expression were assessed at various ages.ResultsGenetic diversity significantly impacts AD-related pathology. Hybrid strains showed resistance to amyloid plaque formation and neuronal damage. Transcriptome diversity was maintained across ages and sexes, with observable strain-specific variations in AD-related phenotypes. Comparative gene expression analysis indicated correlations between mouse strains and human AD.DiscussionIncreasing genetic diversity promotes resilience to AD-related pathogenesis, relative to an inbred C57BL/6J background, reinforcing the importance of genetic diversity in uncovering resilience in the development of AD.HighlightsGenetic diversity's impact on AD in mice was explored. Diverse F1 mouse strains were used for AD study, via the Collaborative Cross. Strain-specific variations in AD pathology, glia, and transcription were found. Strains resilient to plaque formation and plasma neurofilament light chain (NfL) increases were identified. Correlations with human AD transcriptomics were observed.

IntroductionThe BIN1 coding variant rs138047593 (K358R) is linked to Late-Onset Alzheimer's Disease (LOAD) via targeted exome sequencing.MethodsTo elucidate the functional consequences of this rare coding variant on brain amyloidosis and neuroinflammation, we generated BIN1K358R knock-in mice using CRISPR/Cas9 technology. These mice were subsequently bred with 5xFAD transgenic mice, which serve as a model for Alzheimer's pathology.ResultsThe presence of the BIN1K358R variant leads to increased cerebral amyloid deposition, with a dampened response of astrocytes and oligodendrocytes, but not microglia, at both the cellular and transcriptional levels. This correlates with decreased neurofilament light chain in both plasma and brain tissue. Synaptic densities are significantly increased in both wild-type and 5xFAD backgrounds homozygous for the BIN1K358R variant.DiscussionThe BIN1 K358R variant modulates amyloid pathology in 5xFAD mice, attenuates the astrocytic and oligodendrocytic responses to amyloid plaques, decreases damage markers, and elevates synaptic densities.HighlightsBIN1 rs138047593 (K358R) coding variant is associated with increased risk of LOAD. BIN1 K358R variant increases amyloid plaque load in 12-month-old 5xFAD mice. BIN1 K358R variant dampens astrocytic and oligodendrocytic response to plaques. BIN1 K358R variant decreases neuronal damage in 5xFAD mice. BIN1 K358R upregulates synaptic densities and modulates synaptic transmission.

The absence of a natural animal model is one of the main challenges in Alzheimers disease research. Despite the challenges of using nonhuman primates in studies, these animals can bridge mouse models and humans, as nonhuman primates are phylogenetically closer to humans and can spontaneously develop AD-type pathology. The capuchin monkey, a New World primate, has recently attracted attention due to its skill in creating and using instruments. We analyzed one capuchin brain using structural 7 T MRI and performed a neuropathological evaluation of three animals. Alzheimer-type pathology was found in the two of the capuchins. Widespread β-amyloid pathology was observed, mainly in focal deposits with variable morphology and a high density of mature plaques. Notably, plaque-associated dystrophic neurites associated with disruption of axonal transport and early cytoskeletal alteration were frequently found. Unlike in other species of New World monkeys, cerebral arterial angiopathy was not the predominant form of β-amyloid pathology. Additionally, abnormal aggregates of hyperphosphorylated tau, resembling neurofibrillary pathology, were observed in the temporal and frontal cortex. Astrocyte hypertrophy surrounding plaques was found, suggesting a neuroinflammatory response. These findings indicate that aged capuchin monkeys can spontaneously develop Alzheimer-type pathology, indicating that they may be an advantageous animal model for research in Alzheimers disease.

It has recently become well-established that there is a connection between Alzheimers disease pathology and gut microbiome dysbiosis. We have previously demonstrated that antibiotic-mediated gut microbiota perturbations lead to attenuation of Aβ deposition, phosphorylated tau accumulation, and disease-associated glial cell phenotypes in a sex-dependent manner. In this regard, we were intrigued by the finding that a marine-derived oligosaccharide, GV-971, was reported to alter gut microbiota and reduce Aβ amyloidosis in the 5XFAD mouse model that were treated at a point when Aβ burden was near plateau levels. Utilizing comparable methodologies, but with distinct technical and temporal features, we now report on the impact of GV-971 on gut microbiota, Aβ amyloidosis and microglial phenotypes in the APPPS1-21 model, studies performed at the University of Chicago, and independently in the 5X FAD model, studies performed at Washington University, St. Louis.Methods To comprehensively characterize the effects of GV-971 on the microbiota-microglia-amyloid axis, we conducted two separate investigations at independent institutions. There was no coordination of the experimental design or execution between the two laboratories. Indeed, the two laboratories were not aware of each others experiments until the studies were completed. Male and female APPPS1-21 mice were treated daily with 40, 80, or 160 mg/kg of GV-971 from 8, when Aβ burden was detectable upto 12 weeks of age when Aβ burden was near maximal levels. In parallel, and to corroborate existing published studies and further investigate sex-related differences, male and female 5XFAD mice were treated daily with 100 mg/kg of GV-971 from 7 to 9 months of age when Aβ burden was near peak levels. Subsequently, the two laboratories independently assessed amyloid-β deposition, metagenomic, and neuroinflammatory profiles. Finally, studies were initiated at the University of Chicago to evaluate the metabolites in cecal tissue from vehicle and GV-971-treated 5XFAD mice.Results These studies showed that independent of the procedural differences (dosage, timing and duration of treatment) between the two laboratories, cerebral amyloidosis was reduced primarily in male mice, independent of strain. We also observed sex-specific microbiota differences following GV-971 treatment. Interestingly, GV-971 significantly altered multiple overlapping bacterial species at both institutions. Moreover, we discovered that GV-971 significantly impacted microbiome metabolism, particularly by elevating amino acid production and influencing the tryptophan pathway. The metagenomics and metabolomics changes correspond with notable reductions in peripheral pro-inflammatory cytokine and chemokine profiles. Furthermore, GV-971 treatment dampened astrocyte and microglia activation, significantly decreasing plaque-associated reactive microglia while concurrently increasing homeostatic microglia only in male mice. Bulk RNAseq analysis unveiled sex-specific changes in cerebral cortex transcriptome profiles, but most importantly, the transcriptome changes in the GV-971-treated male group revealed the involvement of microglia and inflammatory responses.Conclusions In conclusion, these studies demonstrate the connection between the gut microbiome, neuroinflammation, and Alzheimers disease pathology while highlighting the potential therapeutic effect of GV-971. GV-971 targets the microbiota-microglia-amyloid axis, leading to the lowering of plaque pathology and neuroinflammatory signatures in a sex-dependent manner when given at the onset of Aβ deposition or when given after Aβ deposition is already at higher levels.

INTRODUCTION: Anti-amyloid therapies are at the forefront of efforts to treat Alzheimers disease (AD). Identifying amyloid risk factors may aid screening and intervention strategies. While veterans face increased exposure to risk factors, whether they face a greater neuropathologic amyloid burden is not well understood. METHODS: Male decedents donating to two Alzheimers Disease Research Center (ADRC) brain banks from 1986 to 2018 with categorized neuritic plaque density and neurofibrillary tangles (n = 597) were included. Using generalized ordered logistic regression we modeled each outcomes association with military history adjusting for age and death year. RESULTS: Having served in the military (60% of sample) is associated with post mortem neuritic amyloid plaque (for each comparison of higher to lower C scores OR = 1.26; 95% confidence interval [CI] = 1.06-1.49) and tau pathology (B score OR = 1.10; 95% CI = 1.08-1.12). DISCUSSION: This is the first study, to our knowledge, finding increased levels of verified AD neuropathology in those with military service. Targeted veteran AD therapies is a pressing need.

Cerebellar amyloid-β (Aβ) plaques are a component of the diagnostic criteria used in Thal staging and ABC scoring for Alzheimer disease (AD) neuropathologic change. However, Aβ deposits in this anatomic compartment are unique and under-characterized; and their relationship with other pathological findings are largely undefined. In 73 cases of pure or mixed AD with an A3 score in the ABC criteria, parenchymal (plaques) and vascular (cerebral amyloid angiopathy [CAA]) cerebellar Aβ-42 deposits were characterized with respect to localization, morphology, density, and intensity. Over 85% of cases demonstrated cerebellar Aβ-42 parenchymal staining that correlated with a Braak stage V-VI/B3 score (p

Accurate and scalable quantification of amyloid-β (Aβ) pathology is crucial for deeper disease phenotyping and furthering research in Alzheimer Disease (AD). This multidisciplinary study addresses the current limitations on neuropathology by leveraging a machine learning (ML) pipeline to perform a granular quantification of Aβ deposits and assess their distribution in the temporal lobe. Utilizing 131 whole-slide-images from consecutive autopsied cases at the University of California Davis Alzheimer Disease Research Center, our objectives were threefold: (1) Validate an automatic workflow for Aβ deposit quantification in white matter (WM) and gray matter (GM); (2) define the distributions of different Aβ deposit types in GM and WM, and (3) investigate correlates of Aβ deposits with dementia status and the presence of mixed pathology. Our methodology highlights the robustness and efficacy of the ML pipeline, demonstrating proficiency akin to experts' evaluations. We provide comprehensive insights into the quantification and distribution of Aβ deposits in the temporal GM and WM revealing a progressive increase in tandem with the severity of established diagnostic criteria (NIA-AA). We also present correlations of Aβ load with clinical diagnosis as well as presence/absence of mixed pathology. This study introduces a reproducible workflow, showcasing the practical use of ML approaches in the field of neuropathology, and use of the output data for correlative analyses. Acknowledging limitations, such as potential biases in the ML model and current ML classifications, we propose avenues for future research to refine and expand the methodology. We hope to contribute to the broader landscape of neuropathology advancements, ML applications, and precision medicine, paving the way for deep phenotyping of AD brain cases and establishing a foundation for further advancements in neuropathological research.

PurposeInflamed, prone-to-rupture coronary plaques are an important cause of myocardial infarction and their early identification is crucial. Atherosclerotic plaques are characterized by overexpression of the type-2 somatostatin receptor (SST2) in activated macrophages. SST2 ligand imaging (e.g. with [68 Ga]Ga-DOTA-TOC) has shown promise in detecting and quantifying the inflammatory activity within atherosclerotic plaques. However, the sensitivity of standard axial field of view (SAFOV) PET scanners may be suboptimal for imaging coronary arteries. Long-axial field of view (LAFOV) PET/CT scanners may help overcome this limitation. We aim to assess the ability of [68 Ga]Ga-DOTA-TOC LAFOV-PET/CT in detecting calcified, SST2 overexpressing coronary artery plaques.MethodsIn this retrospective study, 108 oncological patients underwent [68 Ga]Ga-DOTA-TOC PET/CT on a LAFOV system. [68 Ga]Ga-DOTA-TOC uptake and calcifications in the coronary arteries were evaluated visually and semi-quantitatively. Data on patients' cardiac risk factors and coronary artery calcium score were also collected. Patients were followed up for 21.5 ± 3.4 months.ResultsA total of 66 patients (61.1%) presented with calcified coronary artery plaques. Of these, 32 patients had increased [68 Ga]Ga-DOTA-TOC uptake in at least one coronary vessel (TBR: 1.65 ± 0.53). Patients with single-vessel calcifications showed statistically significantly lower uptake (SUVmax 1.10 ± 0.28) compared to patients with two- (SUVmax 1.31 ± 0.29, p

• Advances in single-cell biology have revolutionized the understanding of atherosclerosis, highlighting the interaction between different cell populations and molecular pathways in plaque progression and regression. • The formation and progression of atherosclerotic plaques are driven by LDL cholesterol and chronic exposure to pro-inflammatory stimuli, resulting in endothelial dysfunction and the formation of foam cells. • The concept of "vulnerable plaque" describes plaques prone to rupture, erosion, or calcified nodules, leading to acute coronary syndrome (ACS). Modern imaging techniques like IVUS, NIRS, and OCT are crucial for identifying and assessing these high-risk plaques. • Intensive lipid-lowering therapies, particularly statins and PCSK9 inhibitors, have shown efficacy in reducing plaque volume and stabilizing plaque features, with ongoing research needed to confirm their long-term benefits in reducing cardiovascular events. Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of death globally despite advances in preventive therapies. Understanding of the initiation and progression of atherosclerosis, the interplay between lipoproteins, endothelial dysfunction, inflammation, and immune responses is critical to treating this disease. The development of vulnerable coronary plaques prone to thrombosis, can lead to acute coronary syndromes, for these reasons, the potential plaque stabilization and regression through pharmacological interventions, particularly lipid-lowering agents like statins and PCSK9 inhibitors is crucial. The imaging techniques such as intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS), and optical coherence tomography (OCT) play a key role in assessing plaque composition and guiding interventional therapeutic strategies. Clinical evidence supports the efficacy of intensive lipid-lowering therapy in inducing plaque regression, with studies demonstrating reductions in plaque volume and improvements in plaque morphology assessed by IVUS, OCT and NIRS. While pharmacological interventions show promise in promoting plaque regression and stabilization, their impact on long-term cardiovascular events requires further investigation. Multimodality imaging and comprehensive outcome trials are proposed as essential tools for elucidating the relationship between plaque modification and clinical benefit in coronary atherosclerosis. The stabilization or regression of atherosclerotic plaque might serve as the phenomenon linking the reduction in LDL-C levels to the decrease in cardiovascular events. Overall, this review emphasizes the ongoing efforts to advance our understanding of ASCVD pathophysiology and optimize therapeutic approaches for improving patient outcomes. [Display omitted] [ABSTRACT FROM AUTHOR]

ABSTRACT Clusters of similar or dissimilar objects are encountered in many fields. Frequently used approaches treat each cluster's central object as latent. Yet, often objects of one or more types cluster around objects of another type. Such arrangements are common in biomedical images of cells, in which nearby cell types likely interact. Quantifying spatial relationships may elucidate biological mechanisms. Parent‐offspring statistical frameworks can be usefully applied even when central objects (“parents”) differ from peripheral ones (“offspring”). We propose the novel multivariate cluster point process (MCPP) to quantify multi‐object (e.g., multi‐cellular) arrangements. Unlike commonly used approaches, the MCPP exploits locations of the central parent object in clusters. It accounts for possibly multilayered, multivariate clustering. The model formulation requires specification of which object types function as cluster centers and which reside peripherally. If such information is unknown, the relative roles of object types may be explored by comparing fit of different models via the deviance information criterion (DIC). In simulated data, we compared a series of models' DIC; the MCPP correctly identified simulated relationships. It also produced more accurate and precise parameter estimates than the classical univariate Neyman–Scott process model. We also used the MCPP to quantify proposed configurations and explore new ones in human dental plaque biofilm image data. MCPP models quantified simultaneous clustering of Streptococcus and Porphyromonas around Corynebacterium and of Pasteurellaceae around Streptococcus and successfully captured hypothesized structures for all taxa. Further exploration suggested the presence of clustering between Fusobacterium and Leptotrichia, a previously unreported relationship. [ABSTRACT FROM AUTHOR]

Background: A systematic review of the evidence was conducted to assess the efficacy of low-intensity extracorporeal shock wave therapy (LI-ESWT) for patients with Peyronie's Disease (PD). Methods: A comprehensive search of the Cochrane Registry, PubMed and Embase databases was conducted to identify all controlled trials, including randomised controlled trials (RCTs), cohort studies and case-control studies, focusing on the efficacy of LI-ESWT in treating PD, and published before February 2023. The size of plaques, curvature deviation, visual analog scale [VAS] and International Index of Erectile Function (IIEF) were the most commonly used tool to evaluate the treatment effectiveness of LI-ESWT. Results: There were 7 studies including 475 patients from 1999 to 2023. The meta-analysis of the data revealed that LI-ESWT could considerably enhance the proportion of men experiencing a reduction in penile plaques (RD 0.27, 95% CI: 0.04–0.50, P = 0.02), improvement in penile curvature (RD: 0.13; 95% CI, 0–0.26; p = 0.05), alleviation of pain (RD 0.22, 95% CI: 0.01–0.42, P = 0.04), and complete remission (RD 0.38, 95% CI 0.23–0.52, P < 0.00001). However, there were no significant differences in improvement of sexual function (MD: 1.44; 95% CI, -3.10–5.97; p = 0.53) between LI-ESWT and the placebo group. Conclusions: According to these studies, LI-ESWT has the potential to decrease plaque size and improve penile curvature or pain in men with PD. The publication of robust evidence from additional well-designed long-term multicenter randomized controlled trials would provide more confidence regarding use of these devices in patients with PD. [ABSTRACT FROM AUTHOR]

Objective: To observe the value of superb micro-vascular imaging (SMI) in evaluating carotid atherosclerotic plaque neovascularization in patients with ischemic stroke. Methods: One hundred patients with ischemic stroke and carotid atherosclerotic plaques from January 2022 to December 2023 were selected. All patients underwent SMI examination and histopathological examination of plaque. The detection of neovascularization in the plaque was compared between the two methods. According to pathological results, the patients were divided into observation group (with neovascularization) and control group (without neovascularization). SMI scores and plaque characteristics of the two groups were compared. Results: Among the 100 patients included in this study, 81 patients were diagnosed with neovascularization through pathological examination and 78 patients were diagnosed with neovascularization through SMI examination. Kappa test showed that the coefficient of consistency between SMI examination and pathological examination was 0.78. ROC curves indicated that the sensitivity, specificity and accuracy of SMI for diagnosing neovascularization were 93.83%, 89.47% and 93.00%. The MVD value of neovascularization with SMI score of 2 was the highest, followed by that with SMI score of 1. The MVD value of neovascularization with SMI score of 0 was the lowest (P<0.05). SMI score, plaque length, thickness, calcification and fibrosis degree of the observation group were higher than those of the control group (P<0.05). Multivariate logistic regression analysis found that SMI score, plaque thickness and calcification degree were independent influencing factors of carotid atherosclerotic plaque neovascularization in patients with ischemic stroke(P<0.05). Spesrman correlation analysis showed that SMI score, plaque thickness and calcification degree were positively correlated with neovascularization (P<0.05). Conclusion: SMI can help to evaluate carotid atherosclerotic plaque neovascularization in patients with ischemic stroke accurately. SMI score, plaque thickness and calcification degree are closely related to carotid atherosclerotic plaque neovascularization in patients with ischemic stroke. Therefore, it is recommended to pay close attention to these factors. [ABSTRACT FROM AUTHOR]

Background: Amyloid-ß (Aß) peptide accumulation in the brain is a pathological hallmark of Alzheimer disease (AD). Because of the relationship between the Aß plaque formation and AD progression, targeting Aß has been advocated as a treatment strategy for this disease. Several studies have focused on immunotherapy methods, such as different vaccination approaches. Materials & Methods: In this systematic review, we explored the main features of the vaccines used to date, including their efficiency in inducing anti-Aß antibodies and removing Aß plaques. We also summarized the reported clinical outcomes and mortality rates. A total of 29 articles written in English that describe human clinical trials using three different vaccines (AN1792, CAD106 and AADVac) were reviewed. Results: Based on these studies, most of the patients who received one of these vaccines showed a significant anti-Aß antibody response at some point during the trial. Several studies reported a decline in Aß plaque load and an increase in Aß phagocytosis in different brain regions. The time intervals between the initial vaccination and the booster doses vary among studies, but a 30-day interval has been suggested as the most appropriate by most studies. Meningoencephalitis, microhemorrhages, amyloid encephalopathy, allergic dermatitis and atrial fibrillation have been reported as the most common adverse effects in vaccinated patients. Conclusion: Clinical investigations have shown improved functional and cognitive outcomes, such as the mini-mental state examination score (MMSE), for vaccinated patients compared to the control groups. However, more human clinical studies are needed for a more conclusive evaluation of the properties of different vaccines. [ABSTRACT FROM AUTHOR]

BACKGROUND: Plaque quantification from coronary computed tomography angiography has emerged as a valuable predictor of cardiovascular risk. Deep learning can provide automated quantification of coronary plaque from computed tomography angiography. We determined per-patient age- and sex-specific distributions of deep learning--based plaque measurements and further evaluated their risk prediction for myocardial infarction in external samples. METHODS: In this international, multicenter study of 2803 patients, a previously validated deep learning system was used to quantify coronary plaque from computed tomography angiography. Age- and sex-specific distributions of coronary plaque volume were determined from 956 patients undergoing computed tomography angiography for stable coronary artery disease from 5 cohorts. Multicenter external samples were used to evaluate associations between coronary plaque percentiles and myocardial infarction. RESULTS: Quantitative deep learning plaque volumes increased with age and were higher in male patients. In the combined external sample (n=1847), patients in the ≥75th percentile of total plaque volume (unadjusted hazard ratio, 2.65 [95% CI, 1.47-4.78]; P=0.001) were at increased risk of myocardial infarction compared with patients below the 50th percentile. Similar relationships were seen for most plaque volumes and persisted in multivariable analyses adjusting for clinical characteristics, coronary artery calcium, stenosis, and plaque volume, with adjusted hazard ratios ranging from 2.38 to 2.50 for patients in the ≥75th percentile of total plaque volume. CONCLUSIONS: Per-patient age- and sex-specific distributions for deep learning--based coronary plaque volumes are strongly predictive of myocardial infarction, with the highest risk seen in patients with coronary plaque volumes in the ≥75th percentile. [ABSTRACT FROM AUTHOR]

Atherosclerosis is the foremost vascular disease, precipitating debilitating complications. Although therapeutic strategies have historically focused on reducing cholesterol deposition, recent insights emphasize the pivotal role of inflammation. Innate inflammation significantly contributes to plaque instability and rupture, underscoring the need for intervention across all disease stages. Numerous studies have highlighted the therapeutic potential of targeting innate immune pathways in atherosclerosis, revealing significant advancements in understanding the molecular mechanisms underlying inflammatory processes within arterial lesions. Notably, research has demonstrated that the modulation of microRNA‐146a (miR‐146a) expression impacts innate inflammation, effectively halts atherosclerosis progression, and enhances plaque stability by targeting interleukin‐1 receptor‐associated kinase (IRAK) and activating TNF receptor‐associated factor 6 (TRAF6), a signalling pathway involving toll‐like receptors (TLRs). Understanding the intricate mechanisms involved is crucial. This study provides a comprehensive analysis of the evidence and underlying mechanisms through which miR‐146a exerts its effects. Integrating these findings into clinical practice may herald a transformative era in managing atherosclerotic cardiovascular disease. [ABSTRACT FROM AUTHOR]

Introduction: In the current paper, the "carotid artery calcium score" method is presented with the target to offer a metric method to quantify the amount of calcification in the carotid artery. Model and Definition: The Volume of Interest (VOI) should be extracted and those voxels, with a Hounsfield Unit (HU) value ≥130, should be considered. The total weight value is determined by calculating the sum of the HU attenuation values of all voxels with values ≥130 HU. This value should be multiplied by the conversion factor ("or voxel size") and divided by a weighting factor, the attenuation threshold to consider a voxel as calcified (and therefore 130 HU): this equation determines the Carotid Artery Calcium Score (CACS). Results: In order to provide the demonstration of the potential feasibility of the model, the CACS was calculated in 131 subjects (94 males; mean age 72.7 years) for 235 carotid arteries (in 27 subjects, unilateral plaque was present) considered. The CACS value ranged from 0.67 to 11716. A statistically significant correlation was found (rho value = 0.663, p value =.0001) between the CACS in the right and left carotid plaques. Moreover, a statistically significant correlation between the age and the total CACS was present (rho value = 0.244, p value =.005), whereas no statistically significant difference was found in the distribution of CACS by gender (p =.148). The CACS was also tested at baseline and after contrast and no statistically significant difference was found. Conclusion: In conclusion, this method is of easy application, and it weights at the same time the volume and the degree of calcification in a unique parameter. This method needs to be tested to verify its potential utility, similar to the coronary artery calcium score, for the risk stratification of the occurrence of cerebrovascular events of the anterior circulation. Further studies using this new diagnostic tool to determine the prognostic value of carotid calcium quantification are needed. [ABSTRACT FROM AUTHOR]

We present a real-life case of a very young man with multiple risk factors who progressed rapidly from minimally obstructive non-calcified plaque on computed tomography angiography (CCTA) to severe three-vessel coronary disease presenting with STEMI. It questions the reliability of zero coronary calcium in high-risk subgroups like familial hypercholesterolemia, high Lp(a), and the young. While CCTA can accurately visualize non-calcified plaque, its interpretation requires expertise and clinical judgment should consider both imaging and clinical risk factors for management. Advanced plaque quantification, peri-coronary (PCAT), and epicardial (EAT) adipose tissue could help better-stratified patients but the evidence-based clinical application remains unknown. [ABSTRACT FROM AUTHOR]

Background and Aims The aim of this study was to determine the prognostic value of coronary computed tomography angiography (CCTA)–derived atherosclerotic plaque analysis in ISCHEMIA. Methods Atherosclerosis imaging quantitative computed tomography (AI-QCT) was performed on all available baseline CCTAs to quantify plaque volume, composition, and distribution. Multivariable Cox regression was used to examine the association between baseline risk factors (age, sex, smoking, diabetes, hypertension, ejection fraction, prior coronary disease, estimated glomerular filtration rate, and statin use), number of diseased vessels, atherosclerotic plaque characteristics determined by AI-QCT, and a composite primary outcome of cardiovascular death or myocardial infarction over a median follow-up of 3.3 (interquartile range 2.2–4.4) years. The predictive value of plaque quantification over risk factors was compared in an area under the curve (AUC) analysis. Results Analysable CCTA data were available from 3711 participants (mean age 64 years, 21% female, 79% multivessel coronary artery disease). Amongst the AI-QCT variables, total plaque volume was most strongly associated with the primary outcome (adjusted hazard ratio 1.56, 95% confidence interval 1.25–1.97 per interquartile range increase [559 mm3]; P =.001). The addition of AI-QCT plaque quantification and characterization to baseline risk factors improved the model's predictive value for the primary outcome at 6 months (AUC 0.688 vs. 0.637; P =.006), at 2 years (AUC 0.660 vs. 0.617; P =.003), and at 4 years of follow-up (AUC 0.654 vs. 0.608; P =.002). The findings were similar for the other reported outcomes. Conclusions In ISCHEMIA, total plaque volume was associated with cardiovascular death or myocardial infarction. In this highly diseased, high-risk population, enhanced assessment of atherosclerotic burden using AI-QCT-derived measures of plaque volume and composition modestly improved event prediction. [ABSTRACT FROM AUTHOR]

BACKGROUND: Studies of the neurovascular contribution to dementia have largely focused on cerebral small vessel disease (CSVD), but the role of intracranial atherosclerotic disease (ICAD) remains unknown in the general population. The objective of this study was to determine the risk of incident dementia from ICAD after adjusting for CSVD and cardiovascular risk factors in a US community-based cohort. METHODS: We acquired brain magnetic resonance imaging examinations from 2011 through 2013 in 1980 Black and White participants in the ARIC study (Atherosclerosis Risk in Communities), a prospective cohort conducted in 4 US communities. Magnetic resonance imaging examinations included high-resolution vessel wall magnetic resonance imaging and magnetic resonance angiography to identify ICAD. Of these participants, 1590 without dementia, without missing covariates, and with adequate magnetic resonance image quality were followed through 2019 for incident dementia. Associations between ICAD and incident dementia were assessed using Cox proportional hazard ratios adjusted for CSVD (characterized by white matter hyperintensities, lacunar infarctions, and microhemorrhages), APOE4 genotype (apolipoprotein E gene ε4), and cardiovascular risk factors. RESULTS: The mean age (SD) of study participants was 77.4 (5.2) years. ICAD was detected in 34.6% of participants. After a median follow-up of 5.6 years, 286 participants developed dementia. Compared with participants without ICAD, the fully adjusted hazard ratios (95% CIs) for incident dementia in participants with any ICAD, with ICAD only causing stenosis ≤50%, and with ICAD causing stenosis >50% in ≥1 vessel were 1.57 (1.17-2.11), 1.41 (1.02-1.95), and 1.94 (1.32-2.84), respectively. ICAD was associated with dementia even among participants with low white matter hyperintensities burden, a marker of CSVD. CONCLUSIONS: ICAD was associated with an increased risk of incident dementia, independent of CSVD, APOE4 genotype, and cardiovascular risk factors. The increased risk of dementia was evident even among participants with low CSVD burden, a group less likely to be affected by vascular dementia, and in participants with ICAD causing only low-grade stenosis. Our results suggest that ICAD may partially mediate the effect that cardiovascular risk factors have on the brain leading to dementia. Both ICAD and CSVD must be considered to understand the vascular contributions to cognitive decline. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusions Oral health is an important part of general health and well‐being and shares risk factors, such as poor diet, with obesity. The published literature assessing the association between obesity and oral health in early childhood is sparse and inconsistent. The objective of this study was to investigate associations between overweight/obesity (measured by body mass index) and dental outcomes (caries, plaque index and gingival index) both cross‐sectionally and longitudinally, taking account of potential confounding factors, based on data collected at age 2 and age 5 within the Australian Study of Mothers' and Infants' Life Events Affecting Oral Health (SMILE) birth cohort study.This study used data from 1174 SMILE participants. Associations between overweight/obesity and dental outcomes were assessed using generalized linear regression models for the modified Poisson family with log link to estimate prevalence ratios. Cross‐sectional and longitudinal models were fitted, after minimal and full adjustment for potential confounders.Approximately 12% of the participants were overweight/obese at 2 years and 9% at 5 years. Between 2 and 5 years, the prevalence of caries increased from approximately 4% to 24%, at least mild plaque accumulation increased from 37% to 90% and at least mild inflammation from 27% to 68%. There were no associations between overweight/obesity and the prevalence of dental caries; prevalence ratios (PR) [95% confidence interval (CI)] after adjustment for age and sex were 0.9 (0.3, 2.4) cross‐sectionally at 2 years, 1.0 (0.6, 1.5) cross‐sectionally at 5 years, and 1.0 (0.6, 1.5) for overweight/obesity at 2 years and caries at 5 years. Prevalence ratios were all around the value of 1 for the other dental outcomes and also after adjustment for additional confounders.There were no associations between overweight/obesity and dental caries, plaque index or gingival index in this cohort of preschool children. However, associations may emerge as the children become older, and it will be possible to extend analyses to include data collected at age 7 in the near future. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a chronic inflammatory condition of the arteries and represents the primary cause of various cardiovascular diseases. Despite ongoing progress, finding effective anti-inflammatory therapeutic strategies for atherosclerosis remains a challenge. Here, we assessed the potential of molecular magnetic resonance imaging (MRI) to visualize the effects of 01BSUR, an anti-interleukin-1β monoclonal antibody, for treating atherosclerosis in a murine model. Male apolipoprotein E-deficient mice were divided into a therapy group (01BSUR, 2 × 0.3 mg/kg subcutaneously, n = 10) and control group (no treatment, n = 10) and received a high-fat diet for eight weeks. The plaque burden was assessed using an elastin-targeted gadolinium-based contrast probe (0.2 mmol/kg intravenously) on a 3 T MRI scanner. T1-weighted imaging showed a significantly lower contrast-to-noise (CNR) ratio in the 01BSUR group (pre: 3.93042664; post: 8.4007067) compared to the control group (pre: 3.70679168; post: 13.2982156) following administration of the elastin-specific MRI probe (p < 0.05). Histological examinations demonstrated a significant reduction in plaque size (p < 0.05) and a significant decrease in plaque elastin content (p < 0.05) in the treatment group compared to control animals. This study demonstrated that 01BSUR hinders the progression of atherosclerosis in a mouse model. Using an elastin-targeted MRI probe, we could quantify these therapeutic effects in MRI. [ABSTRACT FROM AUTHOR]

The plaque accumulation is the main cause of gingivitis, patients who wear fixed orthodontic appliances must practice meticulous oral hygiene procedures to prevent a range of problem, such as tooth decay, gingival inflammation, excessive gingival growth, and periodontal disease. manual tooth brush alone insufficient for orthodontic patient, so additional cleaning aids need like interdental brush, single tufted brush and water irrigator, the gingival health can be evaluated by periodontal parameters like plaque index, bleeding on probing and gingival index or by estimation the salivary or GCF concentration of cytokine by Enzyme-linked immunosorbent assay ELISA. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the effects of low tube voltage on coronary plaques and pericoronary fat assessment, and to compare their extent among various levels of low voltage. Materials and methods: Patients were recommended for high-pitch low-tube voltage coronary computed tomography angiography (CCTA), and they were included if they had poor image quality and were referred to a conventional CCTA. The patients were classified into a low-voltage group (with 70-kV, 80-kV, and 90-kV subgroups) and a conventional group (100/120 kV). Their total plaque and subcomponent volumes and pericoronary fat attenuation index (FAI) were measured. Results: A total of 1002 image slices (from 65 patients and 74 plaques) were included, including 21, 31, 13, 4, and 61 patients in the 70-kV, 80-kV, 90-kV, 100-kV, and 120-kV groups respectively. The CT values of noncalcified plaques in the conventional and low-voltage groups were 54.6 ± 21.3 HU and 31.5 ± 22.6 HU, respectively (p < 0.05). Compared with the conventional group, the necrotic core and calcification volume were increased, and the fibrolipid volume, periplaque, and right coronary artery FAI were decreased in the low-voltage group and its subgroups (p < 0.001). The magnitude of changes in fibrous and calcification volumes increased in the 70-kV subgroup compared with that in the 90-kV subgroup (p < 0.05). Conclusion: Low tube voltages, particularly of 70 kV, have a significant effect on coronary plaque and FAI. The effect of low voltage on plaque composition is characterized by a polarization pattern, i.e., a decrease in fibrolipid (medium density) and an increase in necrotic core (low density) and calcification (high density). Clinical relevance statement: Our results highlight the comparability and repeatability of plaque and pericoronary fat assessments facilitated by the same or a similar tube voltage. It is necessary to carry out studies on the specificity threshold of low tube voltage at each level. Key Points: • Low tube voltage had a significant effect on coronary plaque and pericoronary fat, particularly 70 kV. • The effect of low tube voltage on plaque composition shows the shift from medium-density mixed components to low- and high-density components. • It is necessary to correct the specificity threshold or attenuation difference for low tube voltage at each level. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to evaluate the acoustic and thermal properties of a plaque phantom. This is very important for the effective implementation of ultrasound not only in diagnosis but especially in treatment for the future. Material and methods: An evaluation of acoustic and thermal properties of plaque phantoms to test their suitability mainly for ultrasound imaging and therapy was presented. The evaluation included measurements of the acoustic propagation speed using pulse-echo technique, ultrasonic attenuation coefficient using through transmission immersion technique, and absorption coefficient. Moreover, thermal properties (thermal conductivity, volumetric specific heat capacity and thermal diffusivity) were measured with the transient method using a needle probe. Results: It was shown that acoustic and thermal properties of atherosclerotic plaque phantoms fall well within the range of reported values for atherosclerotic plaque and slightly different for thermal diffusivity and volumetric specific heat capacity for soft tissues. The mean value of acoustic and thermal properties and their standard deviation of plaque phantoms were 1523 ± 23 m/s for acoustic speed, 0.50 ± 0.02 W/mK for thermal conductivity, 0.30 ± 0.21 db/cm-MHz for ultrasonic absorption coefficient and 1.63 ± 0.46 db/cm-MHz for ultrasonic attenuation coefficient. Conclusions: This study demonstrated that acoustic and thermal properties of atherosclerotic plaque phantoms were within the range of reported values. Future studies should be focused on the optimum recipe of the atherosclerotic plaque phantoms that mimics the human atherosclerotic plaque (agar 4% w/v, gypsum 10% w/v and butter 10% w/v) and can be used for HIFU therapy. [ABSTRACT FROM AUTHOR]

The feline eosinophilic granuloma complex is a well-known dermatological problem that affects domestic cats. It has three characteristic components: eosinophilic plaque, eosinophilic granuloma and indolent ulcer. In this case report, we report a 5-year-old, mixed-breed cat with pruritic plaque formation, which was typical for eosinophilic plaque by dermatological examination. The diagnosis was established by histopathological and clinical findings. As previous literature showed, hair follicle epitheliummucinosis as a histopathological finding could potentially give us fundamental clues about the microscopic diagnosis of this complex. We discuss the presentation, histopathology and treatment response in detail. This case highlights howintricate feline eosinophilic granuloma complex can be, and underscores the significance of hair follicle epithelium mucinosis as a diagnostic tool in histopathology. [ABSTRACT FROM AUTHOR]

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Intracranial atherosclerotic disease (ICAD) is a common cause of ischaemic stroke and transient ischaemic attack (TIA) with a high recurrence rate. It is often referred to as intracranial atherosclerotic stenosis (ICAS), when the plaque has caused significant narrowing of the vessel lumen. The lesion is usually considered symptomatic ICAD/ICAS (sICAD/sICAS) when it has caused an ischaemic stroke or TIA. The severity of luminal stenosis has long been established as a prognostic factor for stroke relapse in sICAS. Yet, accumulating studies have also reported the important roles of plaque vulnerability, cerebral haemodynamics, collateral circulation, cerebral autoregulation and other factors in altering the stroke risks across patients with sICAS. In this review article, we focus on cerebral haemodynamics in sICAS. We reviewed imaging modalities/methods in assessing cerebral haemodynamics, the haemodynamic metrics provided by these methods and application of these methods in research and clinical practice. More importantly, we reviewed the significance of these haemodynamic features in governing the risk of stroke recurrence in sICAS. We also discussed other clinical implications of these haemodynamic features in sICAS, such as the associations with collateral recruitment and evolution of the lesion under medical treatment, and indications for more individualised blood pressure management for secondary stroke prevention. We then put forward some knowledge gaps and future directions on these topics.

BackgroundPericoronary adipose tissue (PCAT) may influence plaque development through inflammatory mechanisms. We assessed PCAT density, as a measure of pericoronary inflammation, in relationship to coronary plaque among people with human immunodeficiency virus (HIV [PWH]) and to a matched control population.MethodsIn this baseline analysis of 727 participants of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) Mechanistic Substudy, we related computed tomography-derived PCAT density to presence and extent (Leaman score) of coronary artery disease (CAD), noncalcified plaque, coronary artery calcium (CAC), and vulnerable plaque features using multivariable logistic regression analyses. We further compared the PCAT density between PWH and age, sex, body mass index, CAC score, and statin use-matched controls from the community-based Framingham Heart Study (N = 464), adjusting for relevant clinical covariates.ResultsAmong 727 REPRIEVE participants (age 50.8 ± 5.8 years; 83.6% [608/727] male), PCAT density was higher in those with (vs without) coronary plaque, noncalcified plaque, CAC >0, vulnerable plaque, and high CAD burden (Leaman score >5) (P < .001 for each comparison). PCAT density related to prevalent coronary plaque (adjusted odds ratio [per 10 HU]: 1.44; 95% confidence interval, 1.22-1.70; P < .001), adjusted for clinical cardiovascular risk factors, body mass index, and systemic immune/inflammatory biomarkers. Similarly, PCAT density related to CAC >0, noncalcified plaque, vulnerable plaque, and Leaman score >5 (all P ≤ .002). PCAT density was greater among REPRIEVE participants versus Framingham Heart Study (-88.2 ± 0.5 HU versus -90.6 ± 0.4 HU; P < .001).ConclusionsAmong PWH in REPRIEVE, a large primary cardiovascular disease prevention cohort, increased PCAT density independently associated with prevalence and severity of coronary plaque, linking increased coronary inflammation to CAD in PWH.

Abstract Background A systematic review of the evidence was conducted to assess the efficacy of low-intensity extracorporeal shock wave therapy (LI-ESWT) for patients with Peyronie`s Disease (PD). Methods A comprehensive search of the Cochrane Registry, PubMed and Embase databases was conducted to identify all controlled trials, including randomised controlled trials (RCTs), cohort studies and case-control studies, focusing on the efficacy of LI-ESWT in treating PD, and published before February 2023. The size of plaques, curvature deviation, visual analog scale [VAS] and International Index of Erectile Function (IIEF) were the most commonly used tool to evaluate the treatment effectiveness of LI-ESWT. Results There were 7 studies including 475 patients from 1999 to 2023. The meta-analysis of the data revealed that LI-ESWT could considerably enhance the proportion of men experiencing a reduction in penile plaques (RD 0.27, 95% CI: 0.04–0.50, P = 0.02), improvement in penile curvature (RD: 0.13; 95% CI, 0–0.26; p = 0.05), alleviation of pain (RD 0.22, 95% CI: 0.01–0.42, P = 0.04), and complete remission (RD 0.38, 95% CI 0.23–0.52, P

Introduction: Fixed orthodontic appliances create areas of plaque stagnation leading to an increase in the volume, structure, and composition of plaque. This increases the chances of decalcification and white spot lesions. Oil pulling, an ancient practice involving swishing oil in the mouth, has demonstrated a significant reduction in plaque scores after 45 days, and a reduction in salivary Streptococcus mutans concentration in few studies done in nonorthodontic subjects. The aim was to compare the concentration of S. mutans in plaque around orthodontic brackets in patients using oil pulling with sesame oil and those on routine oral hygiene. Subjects and Methods: Twenty subjects requiring fixed orthodontic treatment were divided into two equal groups: Group A-Oil pulling and Group B-Control. All subjects were instructed to follow common oral hygiene methods and in addition, Group A was instructed to perform oil pulling for 30 days starting 1 month after placement of fixed appliances. Plaque specimens were collected from labial surfaces of maxillary lateral incisors and quantification of S. mutans was done using real-time polymerase chain reaction. Mean and standard deviations for descriptive statistics, paired, and unpaired sample t-tests were analyzed. Results: Comparison of S. mutans concentration between T1 and T2 demonstrated a significant difference in both control and study groups. The experimental group showed significantly lesser S. mutans concentration compared to the control group. Conclusions: Oil-pulling therapy with sesame oil resulted in a statistically significant reduction in the concentration of S. mutans in the plaque around orthodontic brackets.

Abstract Atherosclerosis is a chronic inflammatory condition of the arteries and represents the primary cause of various cardiovascular diseases. Despite ongoing progress, finding effective anti-inflammatory therapeutic strategies for atherosclerosis remains a challenge. Here, we assessed the potential of molecular magnetic resonance imaging (MRI) to visualize the effects of 01BSUR, an anti-interleukin-1β monoclonal antibody, for treating atherosclerosis in a murine model. Male apolipoprotein E-deficient mice were divided into a therapy group (01BSUR, 2 × 0.3 mg/kg subcutaneously, n = 10) and control group (no treatment, n = 10) and received a high-fat diet for eight weeks. The plaque burden was assessed using an elastin-targeted gadolinium-based contrast probe (0.2 mmol/kg intravenously) on a 3 T MRI scanner. T1-weighted imaging showed a significantly lower contrast-to-noise (CNR) ratio in the 01BSUR group (pre: 3.93042664; post: 8.4007067) compared to the control group (pre: 3.70679168; post: 13.2982156) following administration of the elastin-specific MRI probe (p

Inflammatory bowel disease (IBD) is a group of chronic, non-specific inflammatory diseases of the gastrointestinal tract including primarily Crohn’s disease and ulcerative colitis, which are affected by multiple factors. Periodontitis is a type of disease characterized by plaque biofilm as the initiating factor and chronic destruction of alveolar bone via resorption. An increasing number of studies have reported a correlation between periodontitis and IBD, but the relationship between the two remains unclear. In this study, we explore the internal relationships between the two diseases from three dimensions, including epidemiological, biological, and associated treatment evidence. Based on epidemiological evidence, periodontitis was found to be associated with an increased risk of IBD, which also affects periodontal health, although the bidirectional correlation needs to be further studied by expanding the number of data sources. From the biological evidence, both clinical studies and animal experiments show that IBD and periodontitis are interconnected. Based on evidence from association therapy, drugs that are beneficial for the treatment of IBD are also effective in the prevention and treatment of periodontitis. In addition, drugs that are good for improving periodontitis can also significantly alleviate IBD. The interaction mechanism between IBD and periodontitis includes the microbial pathway and the immunization route. The microbial pathway refers to the increase in the probability of intestinal tract ectopic colonization by oral bacteria transmitted through the mouth-gut axis or blood, resulting from the increase in the proportion of opportunistic pathogens in the oral cavity of patients with periodontitis and the influence of IBD on the secretion of gastric juice and the balance of intestinal flora. These microorganisms further aggravate IBD inflammation by releasing virulence factors, destroying the intestinal mucosal barrier, and triggering inflammatory responses. In periodontitis, adaptive immunity is activated in the mouth, leading to the production of a large number of immune cells, including Th17 containing the intestinal homing marker α4β7 integrin on their surface. Increased ligand expression of α4β7 integrin in the intestinal mucosa of patients with IBD accelerates oral Th17 cell transfer to the intestine, thereby worsening intestinal inflammation. In parallel, the abnormal expression of cytokines, such as TNF-α, IL-1β, IL-10, IL-6, IL-21, soluble CD40 ligand (sCD40L), IL-23, and INF-γ, in the oral cavity of patients with IBD was observed, suggesting that IBD may affect periodontitis through immunity. These cytokines represent targets for the treatment of both diseases and provide a research direction for their prevention and treatment in the future.

Atherosclerosis is an inflammatory process resulting in the deposition of cholesterol and cellular debris, narrowing of the vessel lumen and clot formation. Characterization of the morphology and vulnerability of the lesion is essential for effective clinical management. Here, near-infrared auto-photoacoustic (NIRAPA) imaging is shown to detect plaque components and, when combined with ultrasound imaging, to differentiate stable and vulnerable plaque. In an ex vivo study of photoacoustic imaging of excised plaque from 25 patients, 88.2% sensitivity and 71.4% specificity were achieved using a clinically-relevant protocol. In order to determine the origin of the NIRAPA signal, immunohistochemistry, spatial transcriptomics and spatial proteomics were co-registered with imaging and applied to adjacent plaque sections. The highest NIRAPA signal was spatially correlated with bilirubin and associated blood-based residue and with the cytoplasmic contents of inflammatory macrophages bearing CD74, HLA-DR, CD14 and CD163 markers. In summary, we establish the potential to apply the NIRAPA-ultrasound imaging combination to detect vulnerable carotid plaque and a methodology for fusing molecular imaging with spatial transcriptomic and proteomic methods.

BACKGROUND: The contemporary burden and characteristics of coronary atherosclerosis, assessed using coronary computed tomography angiography (CCTA), is unknown among asymptomatic adults with diabetes and prediabetes in the United States. The pooled cohort equations and coronary artery calcium (CAC) score stratify atherosclerotic cardiovascular disease risk, but their association with CCTA findings across glycemic categories is not well established. METHODS: Asymptomatic adults without atherosclerotic cardiovascular disease enrolled in the Miami Heart Study were included. Participants underwent CAC and CCTA testing and were classified into glycemic categories. Prevalence of coronary atherosclerosis (any plaque, noncalcified plaque, plaque with ≥1 high-risk feature, maximal stenosis ≥50%) assessed by CCTA was described across glycemic categories and further stratified by pooled cohort equations-estimated atherosclerotic cardiovascular disease risk and CAC score. Adjusted logistic regression was used to evaluate the associations between glycemic categories and coronary outcomes. RESULTS: Among 2352 participants (49.5% women), the prevalence of euglycemia, prediabetes, and diabetes was 63%, 30%, and 7%, respectively. Coronary plaque was more commonly present across worsening glycemic categories (euglycemia, 43%; prediabetes, 58%; diabetes, 69%), and similar pattern was observed for other coronary outcomes. In adjusted analyses, compared with euglycemia, prediabetes and diabetes were each associated with higher odds of any coronary plaque (OR, 1.30 [95% CI, 1.05-1.60] and 1.75 [1.17-2.61], respectively), noncalcified plaque (OR, 1.47 [1.19-1.81] and 1.99 [1.38-2.87], respectively), and plaque with ≥1 high-risk feature (OR, 1.65 [1.14-2.39] and 2.53 [1.48-4.33], respectively). Diabetes was associated with stenosis ≥50% (OR, 3.01 [1.79-5.08]; reference=euglycemia). Among participants with diabetes and estimated atherosclerotic cardiovascular disease risk

The R47H variant of triggering receptor expressed on myeloid cells 2 (TREM2) increases the risk of Alzheimers disease (AD). To investigate potential mechanisms, we analyzed knockin mice expressing human TREM2-R47H from one mutant mouse Trem2 allele. TREM2-R47H mice showed increased seizure activity in response to an acute excitotoxin challenge, compared to wildtype controls or knockin mice expressing the common variant of human TREM2. TREM2-R47H also increased spontaneous thalamocortical epileptiform activity in App knockin mice expressing amyloid precursor proteins bearing autosomal dominant AD mutations and a humanized amyloid-β sequence. In mice with or without such App modifications, TREM2-R47H increased the density of putative synapses in cortical regions without amyloid plaques. TREM2-R47H did not affect synaptic density in hippocampal regions with or without plaques. We conclude that TREM2-R47H increases AD-related network hyperexcitability and that it may do so, at least in part, by causing an imbalance in synaptic densities across brain regions.

Background Residual risk of cardiovascular events and plaque progression remains despite reduction in low-density lipoprotein cholesterol. Factors contributing to residual risk remain unclear. The authors examined the role of eicosapentaenoic acid and docosahexaenoic acid in coronary plaque regression and its predictors. Methods and Results A total of 240 patients with stable coronary artery disease were randomized to eicosapentaenoic acid plus docosahexaenoic acid (3.36 g/d) or none for 30 months. Patients were stratified by regression or progression of coronary fatty plaque measured by coronary computed tomographic angiography. Cardiac events were ascertained. The mean±SD age was 63.0±7.7 years, mean low-density lipoprotein cholesterol level was

Determining the mechanical characteristics of the artery is very essential for the production of vascular implants. In the present work, the mechanical characteristics of arterial walls were investigated by considering plaque and stent in a 3D model. This article aims to investigate the effect of the arterial tissue with the same boundary conditions and restrictions for an artery blocked with the plaque and stent, in creating stress in the tissue. An intravascular stent implantation is a treatment method whose success largely depends on the mechanical characteristics of each vascular component, plaque and stent, and blood flow pressure. For opening up the blood flow in the blocked artery, stents could be used as medical devices. In this research, a stent was designed, and its impact on all three models of elastic, viscoelastic, and hyper-elastic arterial tissue with plaque was studied and compared. An ideal finite element model was made to find the effect of three types of the artery tissue (elastic, viscoelastic, hyper-elastic) with the systolic and diastolic blood flow pressure to observe the stress and the deformation of arteries, plaques, and stents. In addition, for the hyper-elastic model, two Mooney-Rivlin and Ogden models were also investigated. It was found that the type of artery had an effective impact on the result of the stress and the deformation created in the stented artery. Moreover, the results illustrated that considering different models for the artery tissue affected the plaque and stent behavior. Arteries exhibit interesting mechanical behaviors. In the present study, an attempt was made to investigate different mechanical behaviors of arteries with the plaque and stent obstruction. In the examined models, the stress for the artery and plaque was higher in the Ogden model and the lowest one was in the viscoelastic model, and the deformation was higher in the viscoelastic model and lower in the Ogden model. It should be noted that the average stress for the vessel in the Ogden model was about 50% higher than the viscoelastic model. Pathological changes in the walls of the vessels can lead to high-risk cardiovascular diseases such as heart attacks and strokes. Understanding arterial mechanical behaviors provides valuable insight into disease. Therefore, the investigation of different behavioral models helps to evaluate the behavior of the arterial wall by considering the composition and function of the tissue. [ABSTRACT FROM AUTHOR]

Abstract The anatomical features spanning from the aortic arch to the proximal carotid artery and the associated cardiovascular risks might significantly influence the development of right carotid plaque. Our research aimed to compare these anatomical and risk factors between individuals with no carotid plaque and those with moderate right-side carotid plaque within a Korean cohort. We conducted a retrospective, cross-sectional analysis involving 413 participants, categorized into a normal group (n = 339) and a right moderate carotid plaque group (defined as > 50% stenosis based on NASCET criteria) (n = 74). We collected data on cardiovascular risk factors and conducted laboratory tests. A 3D model of the carotid artery was constructed using cranio-cervical computed tomography angiography (CTA) data through semi-automated software. Measurements taken on this 3D model included the common carotid artery (CCA), internal carotid artery (ICA), external carotid artery (ECA), and carotid artery bifurcation (CAB) in terms of maximal vascular diameter, sectional area, angles of carotid bifurcation and ICA, and carotid tortuosity. When compared with the normal group, individuals in the right moderate carotid plaque group exhibited smaller angles at the carotid bifurcation, larger CCA diameter and sectional area (p

Context: The primary objective of using dentifrice is to remove plaque biofilm from tooth surfaces and additionally protect teeth from sequelae of events – halitosis, gingivitis, periodontal inflammation, and dental caries. Aim: The aim of this study was to evaluate the effectiveness and consumer satisfaction profile of using herbal and nonherbal dentifrice in controlling dental plaque. Settings and Design: The randomized clinical trial was conducted on dental students at K. D. Dental College and Hospital, Mathura. Subjects and Methods: The triple-blinded trial was conducted during July 2022 over 15 days among 50 dental students of the institute, aged 18–21 years selected using simple random sampling and allocated into two groups: Group A – herbal dentifrice (Patanjali Dant Kanti dentifrice) and Group B – nonherbal dentifrice (Colgate dentifrice). At baseline, open ended self administered questionnaire regarding general information was recorded followed by full mouth prophylaxis and instructions to brush twice daily with allocated dentifrice following modified bass technique. Plaque assessment was done for index teeth on the 7th and 15th days using the plaque index. Statistical Analysis Used: The data were analyzed using SPSS. Intergroup comparisons were done using paired t-test and descriptive statistics for consumer satisfaction profile assessment. Results: The mean plaque index scores for Groups A and B was reduced at 15th day in comparison to scores on 7th day. Consumer satisfaction feedback was found statistically significant for Group A with insignificant for Group B on few parameters. Conclusions: Herbal dentifrice had similar antiplaque efficacy to nonherbal dentifrice with satisfactory consumer feedback without side effects on using them.

Background: Effective plaque control is essential for improved oral health. Advancements in mechanical plaque removal using toothbrushes still continue. One such sophisticated intervention is the app-based toothbrush, a new innovative technology that helps to track the child’s brushing habits. Aim: The aim of this study is to evaluate the plaque removal efficacy of three different toothbrushes in children aged 6–8 years. Methods: A randomized controlled clinical trial was conducted among primary school children with decayed missing filled teeth (dmft) score of ≤2. Baseline plaque score was collected using Turesky modification of the Quigley and Hein Index 1 week after oral prophylaxis. Children were randomly divided into three groups. Group I received conventional toothbrush (n = 25), group II received powered toothbrush (n = 25), and group III received app-based toothbrush (n = 25). Post-intervention plaque score, toothbrush wear and bite mark scores were done at the 15th, 30th, 45th and 90th day. Participant’s opinion on their toothbrushes was evaluated using a questionnaire. Results and Conclusion: App-based toothbrush showed maximum plaque reduction followed by powered and conventional toothbrush. Significant reduction in plaque score was seen at 30th-, 45th- and 90th-day follow-up in group II (

Xinyan Hu,1,&ast; Yanling Sui,1,&ast; Xinhao Yang,1 Zhengyu Yang,2 Qiuting Wang,2 Jiehong Yuan,2 Maoyu Li,1 Xiaotong Ma,1 Chengxuan Qiu,3 Qinjian Sun1 1Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 2Department of Neurology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, People’s Republic of China; 3Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Stockholm University, Stockholm, Sweden&ast;These authors contributed equally to this workCorrespondence: Qinjian Sun, Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Neurology, Shandong Provincial Hospital affiliated to Shandong First Medical University, No. 324 Jingwu Weiqi Road, Jinan, Shandong, 250021, People’s Republic of China, Email sqj1210@163.comBackground: The inflammatory response is a pivotal factor in accelerating the progression of atherosclerosis. The high-sensitivity C-reactive protein-to-albumin ratio (CAR) has emerged as a novel marker of systemic inflammation. However, few studies have shown the CAR to be a promising prognostic marker for carotid atherosclerotic disease. This study aimed to analyse the predictive role of the CAR in carotid atherosclerotic disease.Methods: This community-based cohort study recruited 2003 participants from the Rose asymptomatic IntraCranial Artery Stenosis (RICAS) study who were free of stroke or transient ischemic attack. Carotid atherosclerotic plaques and their stability were identified via carotid ultrasound. Logistic regression models were utilized to investigate the association between CAR and the presence of carotid atherosclerotic plaques.Results: The prevalence of carotid atherosclerotic plaques was 38.79% in this study. After adjusting for clinical risk factors, including sex, age, dyslipidemia, hypertension, diabetes mellitus (DM), and smoking and drinking habits, a high CAR-level was independently associated with carotid plaque (odds ratio [OR] of upper: 1.46, 95% confidence interval [CI]: 1.13– 1.90, P = 0.004; P for trend = 0.011). The highest CAR tertile was still significantly associated with carotid plaques among middle-aged (40– 64 years) or female participants. Notably, an elevated CAR may be an independent risk factor for vulnerable carotid plaques (OR of upper: 2.06, 95% CI: 1.42– 2.98, P < 0.001; P for trend < 0.001).Conclusion: A high CAR may be correlated with a high risk of carotid plaques, particularly among mildly aged adults (40– 64 years) or females. Importantly, the CAR may be associated with vulnerable carotid plaques, suggesting that the CAR may be a new indicator for stroke prevention. Keywords: C-reactive protein, albumin, plaque, atherosclerotic, cohort study