Search

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

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]

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 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 < 0.01), advanced age, and a higher incidence of hypertension, diabetes, and stroke history (p < 0.05), along with reduced glomerular filtration rate (GFR) (p < 0.001). Multivariate analysis revealed that the sectional area of the bifurcation, calcification of the aortic bulb, and GFR were independently associated with the presence of right moderate carotid plaque (p < 0.01). Statistical analyses disclosed significant differences in both clinical risk factors and geometric changes in the region extending from the aortic arch to the proximal carotid artery among subjects with right moderate carotid plaque when compared to those without. [ABSTRACT FROM AUTHOR]

Aim: Atherosclerosis remains the pathological basis of myocardial infarction and ischemic stroke. Early and accurate identification of plauqes is crucial to improve clinical outcomes of atherosclerosis patients. Our study aims to evaluate the potential value of fibroblast activation protein inhibitor (FAPI)-04 PET/CT in identifying plaques via a preclinical rabbit model of atherosclerosis. Methods: New Zealand white rabbits were fed high-fat diet (HFD), and randomly divided into the model group injured by the balloon, and the sham group only with incisions. Ultrasound was performed to detect plaques, and FAPI-avid was determined through Al18F-NOTA-FAPI-04 PET/CT. Mean standardized uptake values (SUVmean) in lesions were compared, and biodistribution of Al18F-NOTA-FAPI-04 and target-to-background ratios (TBRs) were calculated. Histological staining was performed to display arterial plaques, and autoradiography (ARG) was employed to measure the in vitro intensity of Al18F-NOTA-FAPI-04. At last, the correlation among FAP levels, plaque area, SUVmean values and fibrous cap thickness was assessed. Results: The rabbit carotid and abdominal atherosclerosis model was established. Al18F-NOTA-FAPI-04 showed a higher uptake in carotid plaques (SUVmean 1.32 ± 0.11) and abdominal plaques (SUVmean 0.73 ± 0.13) compared to corresponding controls (SUVmean 1.07 ± 0.06; 0.46 ± 0.03) (P < 0.05). Biodistribution analysis of Al18F-NOTA-FAPI-04 revealed that the bigger plaques were delineated with higher TBRs. Pathological staining showed the formation of arterial plaques, and ARG staining exhibited a higher intensity of Al18F-NOTA-FAPI-04 in the bigger plaques. Lastly, plaque area was found to be positively correlated to FAP expression and SUVmean, while FAP expression was negatively correlated to fibrous cap thickness of plaques. Conclusions: We successfully achieve molecular imaging of fibroblast activation in atherosclerotic lesions of rabbits, suggesting Al18F-NOTA-FAPI-04 PET/CT may be a potentially valuable tool to identify plaques. [ABSTRACT FROM AUTHOR]

Background: Depression is the most common mental illness worldwide and generates an enormous health and economic burden. Furthermore, it is known to be associated with an elevated risk of arteriosclerotic cardiovascular diseases (ASCVD), particularly stroke. However, it is not a factor reflected in many ASCVD risk models, including SCORE2. Thus, we analysed the relationship between depression, ASCVD and SCORE2 in our cohort. Methods: We analysed 9350 subjects from the Paracelsus 10,000 cohort, who underwent both a carotid artery ultrasound and completed a Beck Depression Inventory (BDI) screening. Patients were categorised binomially based on the BDI score. Atherosclerotic carotid plaque or absence was dichotomised for logistic regression modelling. Odds ratios and adjusted relative risks were calculated using Stata. Results: Subjects with an elevated BDI (≥14) had higher odds for carotid plaques compared to subjects with normal BDI, especially after adjusting for classical risk factors included in SCORE2 (1.21; 95%CI 1.03–1.43, p = 0.023). The adjusted relative risk for plaques was also increased (1.09; 95%CI 1.01–1.18, p = 0.021). Subgroup analysis showed an increased odds of plaques with increases in depressive symptoms, particularly in women and patients ≤55 yrs. Conclusions: In our cohort, the BDI score is associated with subclinical atherosclerosis beyond classical risk factors. Thus, depression might be an independent risk factor which may improve risk stratification if considered in ASCVD risk prediction models, such as SCORE2. Furthermore, reminding clinicians to take mental health into consideration to identify individuals at increased atherosclerosis risk may provide added opportunities to address measures which can reduce the risk of ASCVD. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to evaluate the impact of the uninstructed use of a toothpaste containing herbal ayurvedic ingredients on parameters of gingival health in a cohort of periodontal aftercare patients affected by gingival inflammation compared to the use of a standard, non‐herbal toothpaste. Materials and Methods: The monocentric, randomized, double‐blinded, two‐arm parallel‐group intervention was performed in a cohort of 88 periodontal aftercare patients with clinical signs of gingival inflammation. At baseline, bleeding on probing (BoP), gingival index (GI) and Quigley–Hein plaque index (QHI) were recorded. Subsequently, the study patients were randomly provided with a herbal ayurvedic toothpaste (n = 44) or a conventional, non‐ayurvedic control toothpaste (n = 44) and without additional oral hygiene training instructed to use it 2× daily for the next 28 days. On day 28, BoP, GI and QHI were recorded again. Results: At baseline, there were no significant differences between both groups. On day 28, mean GI and BoP scores were significantly lower (p < 0.001) compared to baseline in both groups. Differences between the groups could not be verified. Mean QHI scores did not change significantly between day 0 and day 28 in both groups. Conclusions: The impact of uninstructed toothbrushing with an ayurvedic toothpaste on the manifestation of gingival inflammation in periodontal aftercare patients is not significantly different to the use of a conventional, non‐herbal toothpaste. [ABSTRACT FROM AUTHOR]

Background and objective: To investigate the use of high-resolution magnetic resonance imaging (HR-MRI) to identify the characteristics of culprit plaques in intracranial arteries, and to evaluate the predictive value of the characteristics of culprit plaques combined with the modified Essen score for the recurrence risk of high-risk non-disabling ischemic cerebrovascular events (HR-NICE) patients. Methods: A retrospective analysis was conducted on 180 patients with HRNICE at the First Affiliated Hospital of Xinxiang Medical University, including 128 patients with no recurrence (non-recurrence group) and 52 patients with recurrence (recurrence group). A total of 65 patients with HR-NICE were collected from the Sixth Affiliated Hospital of Shanghai Jiaotong University as a validation group, and their modified Essen scores, high-resolution magnetic resonance vessel wall images, and clinical data were collected. The culprit plaques were analyzed using VesselExplorer2 software. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for recurrence, and a nomogram was constructed using R software to evaluate the discrimination of the model. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) was used to evaluate the model performance. Calibration curves and Decision Curve Analysis (DCA) were used to evaluate the model efficacy. Results: Intra-plaque hemorrhage (OR  =  3.592, 95% CI  =  1.474–9.104, p  =  0.006), homocysteine (OR  =  1.098, 95% CI  =  1.025–1.179, p  =  0.007), and normalized wall index (OR  =  1.114, 95% CI  =  1.027–1.222, p  =  0.015) were significantly higher in the recurrent stroke group than in the non-recurrent stroke group, and were independent risk factors for recurrent stroke. The performance of the nomogram model (AUC  =  0.830, 95% CI: 0.769–0.891; PR-AUC  =  0.628) was better than that of the modified Essen scoring model (AUC  =  0.660, 95% CI: 0.583–0.738) and the independent risk factor combination model (AUC  =  0.827, 95% CI: 0.765–0.889). The nomogram model still had good model performance in the validation group (AUC  =  0.785, 95% CI: 0.671–0.899), with a well-fitting calibration curve and a DCA curve indicating good net benefit efficacy for patients. Conclusion: High-resolution vessel wall imaging combined with a modified Essen score can effectively assess the recurrence risk of HR-NICE patients, and the nomogram model can provide a reference for identifying high-risk populations with good clinical application prospects. [ABSTRACT FROM AUTHOR]

Aim: To assess and compare the effect of mouthwash containing 0.3% Aegle marmelos (Bael) leaves extract with other herbal mouthwashes containing 0.3% Cinnamomum zeylanicum (Cinnamon) barks extract and 0.3% Azadirachta indica (Neem) leaves extract and with 0. 2% chlorhexidine mouthwash on dental plaque, gingival health and salivary p H among adults. Materials and Methods: A triple blinded randomized controlled trial with concurrent parallel study design was carried out. Around, 48 young adults were randomly allotted to four groups - Group A (Chlorhexidine), Group B (Cinnamon), Group C (Bael) and Group D ( Neem) by simple randomization technique. They were advised to rinse with 10 ml of their respected mouthwashes twice daily for 1 minute for a period of 28 days. The dental plaque score and gingival inflammation score were recorded using Plaque index and Gingival index at the baseline, 15th day, 22nd day and 29th day. Statistical analysis were done using ANOVA and repeated measure ANOVA for the plaque and gingival scores and Paired sample t test for p H Results: Mouthwashes containing Bael, Neem and Chlorhexidine showed a stastistically significant reduction in the plaque levels at the end of second week (mean difference from baseline to 2nd week = 0. 158, 0. 100 and 0. 108 respectively with p value < 0. 05). However, at all the time points considered in the study, Bael was more effective in reducing the gingivitis. Conclusion: Bael extract mouthwash is as effective as the gold standard Chlorhexidine mouthwash in reducing the plaque and gingivitis and opens new perspectives for its use. [ABSTRACT FROM AUTHOR]

Background: This cross-sectional study aimed to identify the prevalence of Candida albicans and Malassezia globosa in children with severe early childhood caries and caries-free children in Hong Kong. Methods: This study first recruited a total of 80 children aged between 48 and 72 months old, 40 children with severe early childhood caries, and 40 caries-free children. The children were then further divided into four groups, with 20 children in each group: Group 1: Severe early childhood caries—C. albicans, Group 2: Severe early childhood caries—M. globosa, Group 3: Caries-free—C. albicans and Group 4: Caries-free—M. globosa. Saliva, plaque, and caries lesion samples were collected from participants with severe early childhood caries, while only saliva and plaque samples were collected from caries-free participants. Caries status of the primary molars was assessed using WHO's decayed, missing, and filled tooth index, and the severity of cavitated lesions was determined based on International Caries Diagnosis and Assessment System criteria as caries code 5 or 6. The samples were analyzed using an Internal Transcribed Space and Quantitative Real-Time Polymerase Chain Reaction. Results:C. albicans was more prevalent in saliva and plaque samples of severe early childhood caries than in the caries-free group. Proportion of C. albicans in both saliva and plaque samples differed significantly between severe early childhood caries and caries-free groups (p < 0.05). Within the severe early childhood caries group, the proportion of children with C. albicans varied between 6 and 46%. No significant difference in M. globosa load was found between plaque samples of the severe early childhood caries and caries-free groups (p = 0.159). Conversely, no significant difference in M. globosa load was observed between saliva samples of severe early childhood caries and caries-free groups (p = 0.051). Conclusions: This study demonstrated a strong association between C. albicans and severe early childhood caries. M. globosa was detected in both the caries-free and severe early childhood caries groups, albeit at low levels. [ABSTRACT FROM AUTHOR]

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.

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.

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.

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 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

AIMS: The totality of atherosclerotic plaque derived from coronary computed tomography angiography (CCTA) emerges as a comprehensive measure to assess the intensity of medical treatment that patients need. This study examines the differences in age onset and prognostic significance of atherosclerotic plaque burden between sexes. METHODS AND RESULTS: From a large multi-center CCTA registry the Leiden CCTA score was calculated in 24 950 individuals. A total of 11 678 women (58.5 ± 12.4 years) and 13 272 men (55.6 ± 12.5 years) were followed for 3.7 years for major adverse cardiovascular events (MACE) (death or myocardial infarction). The age where the median risk score was above zero was 12 years higher in women vs. men (64-68 years vs. 52-56 years, respectively, P < 0.001). The Leiden CCTA risk score was independently associated with MACE: score 6-20: HR 2.29 (1.69-3.10); score > 20: HR 6.71 (4.36-10.32) in women, and score 6-20: HR 1.64 (1.29-2.08); score > 20: HR 2.38 (1.73-3.29) in men. The risk was significantly higher for women within the highest score group (adjusted P-interaction = 0.003). In pre-menopausal women, the risk score was equally predictive and comparable with men. In post-menopausal women, the prognostic value was higher for women [score 6-20: HR 2.21 (1.57-3.11); score > 20: HR 6.11 (3.84-9.70) in women; score 6-20: HR 1.57 (1.19-2.09); score > 20: HR 2.25 (1.58-3.22) in men], with a significant interaction for the highest risk group (adjusted P-interaction = 0.004). CONCLUSION: Women developed coronary atherosclerosis approximately 12 years later than men. Post-menopausal women within the highest atherosclerotic burden group were at significantly higher risk for MACE than their male counterparts, which may have implications for the medical treatment intensity.

Recent studies have found an association between high volumes of physical activity and increased levels of coronary artery calcification (CAC) among older male endurance athletes, yet the underlying mechanisms have remained largely elusive. Potential mechanisms include greater exposure to inflammatory cytokines, reactive oxygen species and oxidised low-density lipoproteins, as acute strenuous physical activity has been found to enhance their systemic release. Other possibilities include post-exercise elevations in circulating parathyroid hormone, which can modify the amount and morphology of calcific plaque, and long-term exposure to non-laminar blood flow within the coronary arteries during vigorous physical activity, particularly in individuals with pre-existing atherosclerosis. Further, although the association has only been identified in men, the role of testosterone in this process remains unclear. This brief review discusses the association between high-volume endurance exercise and CAC in older men, elaborates on the potential mechanisms underlying the increased calcification, and provides clinical implications and recommendations for those at risk.

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

Abstract Background Life’s Essential 8 (LE8), the recently updated construct for quantifying cardiovascular health, is related to the risks of cardiovascular events. The present study aimed to evaluate associations of LE8 score with the multi-territorial extent of atherosclerosis in a community-dwelling population. Methods Data were derived from the baseline cross-sectional survey of the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study in Lishui City. The LE8 included overall, medical and behavior LE8 scores, and were categorized as low (

Abstract In 2018, SGS Belgium NV developed RSV-NICA (Respiratory Syncytial Virus-Nasobronchial Infective Challenge Agent), an RSV type A challenge agent for use in RSV Controlled Human Infection Model (CHIM) studies. It is widely recognized that the stability of RSV can be influenced by a variety of environmental parameters, such as temperature and pH. Consequently, our objective was to evaluate the stability of the viral titer of RSV-NICA following five years of controlled storage and to determine the uniformity of the viral titers across different vials of a GMP-qualified batch of RSV-NICA. In addition, we examined the capacity of RSV-NICA to infect human primary airway epithelial cells (MucilAir™), the principal target cells of RSV, and evaluated the influence of single and recurrent freeze–thaw cycles on the infectious viral titer of the challenge agent. The aliquoted RSV-NICA virus stock was subjected to standard virological and molecular methods to gather data on the titer and consistency of the viral titer contained within 24 representative vials of the stock. Our findings illustrate that over a span of five years of cryo-storage, the infectious viral titer in 75% of the tested vials exhibited a comparable average infectious viral titer (4.75 ± 0.06 vs 4.99 ± 0.11; p-value = 0.14). A considerable reduction down to an undetectable level of infectious virus was observed in the remaining vials. RSV-NICA demonstrated its capacity to effectively infect differentiated human airway epithelial cells, with active virus replication detected in these cells through increasing RSV genome copy number over time. Virus tropism for ciliated cells was suggested by the inhibition of cilia beating coupled with an increase in viral RNA titers. No discernable impact on membrane barrier function of the epithelial lung tissues nor cytotoxicity was detected. Pooling of vials with infectious titers > 4.0 log10 TCID50/ml and freeze-thawing of these combined vials showed no deterioration of the infectious titer. Furthermore, pooling and re-aliquoting of vials spanning the entire range of viral titers (including vials with undetectable infectious virus) along with subjecting the vials to three repeated freeze–thaw cycles did not result in a decrease of the infectious titers in the tested vials. Taken together, our findings indicate that long-term cryo-storage of vials containing RSV-NICA challenge agent may influence the infectious viral titer of the virus, leading to a decrease in the homogeneity of this titer throughout the challenge stock. However, our study also demonstrates that when heterogeneity of the infectious titer of an RSV stock is observed, rounds of pooling, re-aliquoting and subsequent re-titration serve as an effective method not only to restore the homogeneity of the infectious titer of an RSV-A stock, but also to optimize patient-safety, scientific and operational aspects of viral inoculation of study participants during at least the period of one RSV CHIM trial. RSV-NICA is a stable, suitable CHIM challenge agent that can be utilized in efficacy trials for RSV vaccines and antiviral entities.

The stainless-steel crown (SSC) is a durable restoration and has several indications for use in primary teeth such as following a pulpotomy/pulpectomy, fractured teeth, teeth with developmental defects, or large multi-surface caries lesions where amalgam is likely to fail. Due to its durability and a lifespan like the primary tooth, it could well be the gold standard in restorative care. SSCs protect the crown from fracture, reduce the possibility for leakage, and ensure a biological seal. However, the placement of the SSC should follow a meticulous technique. There are some clinical situations where the SSC may fail, leading to plaque accumulation and gingivitis. This could be secondary to improper crimping of crown margins, which lead to poorly adapted SSC. In some clinical situations, ledge formation under the crown or failure to clean excess cement can contact the gingiva and cause gingival inflammation. This study was carried out on 41 children between the ages of 4 and 10 in Al Qassim region to study the effects of SSCs on gingiva and oral hygiene. The study also aims to establish the correlation between SSC adaptation and post-insertion inflammation. The plaque and gingival index were recorded at 3 months’ post SSC insertion. Clinical examination was undertaken, and gingival index (Loe and Silness 1967) and plaque index (Silness and Loe 1967) were used to record gingival health and plaque accumulation, respectively. The result for post-inflammation and SSC adaptation showed that there was no statistically significant difference in post-insertion inflammation and crown adaptation (P value = 0.216). The result for pre-operative inflammation and post-operative inflammation shows that there is no significant difference in post-inflammation and adaptation (P value = 0.47). We found that oral hygiene care had a heightening effect and oral hygiene maintenance plays a key role in preventing gingival inflammation irrespective of the SSC adaptation over short periods of time (3 months).

Abstract Background Periodontitis is the most common oral disease in dogs, and its progression and severity are influenced by risk factors, such as age and body size. Recent studies have assessed the canine oral microbiota in relation to different stages of periodontitis and niches within the oral cavity. However, knowledge of the bacterial composition at different ages and body sizes, especially in puppies, is limited. This study aimed to characterize the oral microbiota in the healthy gingiva of small breed puppies using next-generation sequencing. Additionally, we assessed the impact of dental care practices and the presence of retained deciduous teeth on the oral microbiota. Results In this study, plaque samples were collected from the gingival margin of 20 small breed puppies (age, 6.9 ± 0.6 months). The plaque samples were subjected to next-generation sequencing targeting the V3-V4 region of the 16 S rRNA. The microbiota of the plaque samples was composed mostly of gram-negative bacteria, primarily Proteobacteria (54.12%), Bacteroidetes (28.79%), and Fusobacteria (5.11%). Moraxella sp. COT-017, Capnocytophaga cynodegmi COT-254, and Bergeyella zoohelcum COT-186 were abundant in the oral cavity of the puppies. In contrast, Neisseria animaloris were not detected. The high abundance of Pasteurellaceae suggests that this genus is characteristic of the oral microbiota in puppies. Dental care practices and the presence of retained deciduous teeth showed no effects on the oral microbiota. Conclusions In this study, many bacterial species previously reported to be detected in the normal oral cavity of adult dogs were also detected in 6–8-month-old small breed dogs. On the other hand, some bacterial species were not detected at all, while others were detected in high abundance. These data indicate that the oral microbiota of 6–8-month-old small breed dogs is in the process of maturating in to the adult microbiota and may also have characteristics of the small dog oral microbiota.

The rupture of unstable plaques is a major cause of acute cardiovascular events. The early assessment of carotid plaques can significantly reduce the cardiovascular risks, so developing evaluation models suitable for data from different centers is of great clinical importance. This study leverages plaque datasets from multiple centers to develop a Weighted multi-source carotid artery plaque Unsupervised Classification Framework (WUCF). The multi-source domain adaptation module of the WUCF focuses on maintaining feature consistency between each independent source and target center, while also integrating a specialized domain discriminator expert. This ensures that the knowledge from each source center is effectively learned and combined for accurate predictions in the target domain. The experimental evaluation of WUCF, using datasets from three centers, has demonstrated the method's superiority and robustness. [ABSTRACT FROM AUTHOR]