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A sufficient green strength of refractory castables is necessary to avoid damage during demoulding and heating up of refractory linings and prefabricated parts. However, there is a lack of knowledge on the mechanisms underlying the build-up of green strength in refractory castables. This work focuses on how green strength is formed within the matrix of PCE-dispersed and CA cement bonded refractory castables during their setting.Setting was monitored using several measuring methods, such as sonic velocity, amount of hydrate phases formed from CA cement, ζ-potential (stability resp. coagulation of the matrix suspension), porosity, and specific surface area and was linked to the corresponding increase of green strength of refractory castables during setting.Considered by time after adding water, the first stiffening of the refractory castables is related to the collapse of the rheological system of their matrix suspension (coagulation), resulting in a very low increase in green strength (apparent hardening). This stiffening occurs early if Ca-precipitates are formed together with molecules of the dispersing agent (Ca-PCE, PCE with short side chains) or if the amount of pore water is being reduced below a critical value (rheologically stable matrix due to dispersion of hydrate phases by PCE with long side chains). The major increase in green strength occurs when a significant amount of CA cement reacts to hydrate phases and, correspondingly, water is being bonded. This main increase in green strength may occur directly after stiffening (if CA cement is being hydrated quickly) or several hours after stiffening (if the hydration of CA cement is retarded).Regarding the green strength, the predominant factor influencing the build-up of green strength in refractory castables is the reduction of free water in the pores due to its bond in hydrate phases (reduction of a lubricating, interparticle water film). Minor influences are the reduction in porosity (volume expansion by hydration of CA cement), the increase in the specific surface area (hydrate phases are finer than the initial CA cement particles), and the entanglement of plate-like hydrate phases.

Coronavirus disease-19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2 that has rapidly evolved into a pandemic to cause over 600 million infections and more than 6.6 million deaths up to Nov 25, 2022. COVID-19 carries a high mortality rate in severe cases. Co-infections and secondary infections with other micro-organisms, such as bacterial and fungus, further increases the mortality and complicates the diagnosis and management of COVID-19. The current guideline provides guidance to physicians for the management and treatment of patients with COVID-19 associated bacterial and fungal infections, including COVID-19 associated bacterial infections (CABI), pulmonary aspergillosis (CAPA), candidiasis (CAC) and mucormycosis (CAM). Recommendations were drafted by the 7th Guidelines Recommendations for Evidence-based Antimicrobial agents use Taiwan (GREAT) working group after review of the current evidence, using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations in March 2022, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes the epidemiology, diagnostic methods and treatment recommendations for COVID-19 associated infections. The aim of this guideline is to provide guidance to physicians who are involved in the medical care for patients with COVID-19 during the ongoing COVID-19 pandemic.

Treatment of environmental media contaminated with per- and polyfluoroalkyl substances (PFAS) is crucial to mitigate mounting health risks associated with exposure. Colloidal activated carbon (CAC) has shown promise in treating contaminated soils, but understanding the interaction among PFAS during sorption is necessary for optimal remediation. This study investigated the extent to which PFAS of varying chain lengths and functional groups compete for sorption to CAC. Batch tests were conducted with natural soil and spiked water, using CAC at 0.2% w/w to remove seven PFAS with individual starting concentrations up to 0.05 mmol L−1. PFAS sorption to CAC was evaluated in three systems: a composite mixture of all studied compounds, a binary-solute system, and a single-solute system. The sorption experiments exhibited strong PFAS affinity to CAC, with removal rates between 41% and 100%, and solid/liquid partition coefficients (Kd) between 10 and 104 L kg−1. Differences were noticed among the various spiking mixtures, based on perfluorocarbon chain length, functional group, and the starting PFAS concentrations. Competition effects were detected when PFAS were in a multi-solute system, with an average 10% drop in removal, which can evidently become more relevant at higher concentrations, due to the observed non-linearity of the sorption process. The PFAS most vulnerable to competition effects in multi-solute systems were the short-chain perfluoropentanoic acid (PFPeA) and perfluorobutane sulfonic acid (PFBS), with an up to 25% reduction in removal. In bi-solute systems, perfluorooctane sulfonamide (FOSA) dominated over its ionisable counterparts, i.e. perfluorooctane sulfonic acid (PFOS) and perfluorononanoic acid (PFNA), indicating the importance of hydrophobic effects or layer formation in the sorption process. These results underscore the importance of considering competition in PFAS sorption processes when designing and implementing remediation techniques for PFAS-contaminated media.

Background: Subclinical coronary artery calcification (CAC) is a risk factor for adverse cardiovascular events, but studies investigating its association with outcomes in hospitalized patients with COVID-19 are limited. Methods: This was a retrospective study of 457 patients without history of clinical coronary artery disease (CAD) who underwent chest CT imaging during COVID-19 hospitalization at MCW/Froedtert-affiliated hospitals from July 1, 2020 to July 1, 2021. Visually estimated CAC (yes/no) and CAC burden (none/mild/moderate/severe) were recorded from radiology reports. Unadjusted and adjusted regression models were used to assess associations between CAC and hospital length of stay (LOS), ICU admission, mechanical ventilation, and mortality. Results: The mean age was 63.1 ± 15.3 years. Presence of CAC was associated with mechanical ventilation (p = 0.01), ICU admission (p = 0.02), in-hospital or 30-day mortality (p

Atherosclerotic cardiovascular disease risk (ASCVD) is an ongoing epidemic, and lipid abnormalities are its primordial cause. Most individuals suffering a first ASCVD event are previously asymptomatic and often do not receive preventative therapies. The cornerstone of primary prevention has been the identification of individuals at risk through risk calculators based on clinical and laboratory traditional risk factors plus risk enhancers. However, it is well accepted that a clinical risk calculator misclassifies a significant proportion of individuals leading to the prescription of a lipid-lowering medication with very little yield or a missed opportunity for lipid-lowering agents with a potentially preventable event. The development of coronary artery calcium scoring (CAC) and CT coronary angiography (CCTA) provide complementary tools to directly visualize coronary plaque and other risk-modifying imaging components that can potentially provide individualized lipid management.Understanding patient selection for CAC or potentially CCTA and the risk implications of the different parameters provided, such as CAC score, coronary stenosis, plaque characteristics and burden, epicardial adipose tissue, and pericoronary adipose tissue, have grown more complex as technologies evolve. These parameters directly affect the shared decision with patients to start or withhold lipid-lowering therapies, to adjust statin intensity or LDL cholesterol goals. Emerging lipid lowering studies with non-invasive imaging as a guide to patient selection and treatment efficacy, plus the evolution of lipid lowering therapies from statins to a diverse armament of newer high-cost agents have pushed these two fields forward with a complex interaction. This review will discuss existing risk estimators, and non-invasive imaging techniques for subclinical coronary atherosclerosis, traditionally studied using CAC and more recently CCTA with qualitative and quantitative measurements. We will also explore the current data, gaps of knowledge and future directions on the use of these techniques in the risk-stratification and guidance of lipid management.

Background and Aims: We aimed to determine the utility of coronary artery calcium (CAC) for atherosclerotic cardiovascular disease (ASCVD) risk stratification in women with and without early menopause (EM). Methods: To examine the association between CAC and incident ASCVD, we performed Kaplan-Meier survival analysis and multivariable Cox proportional hazards modeling using data from 2,456 postmenopausal women in the Multi-Ethnic Study of Atherosclerosis (MESA) with or without EM, defined as occurring at 50% of middle-aged postmenopausal women with EM had CAC = 0, similar to those without EM. Among women with CAC = 0, those with EM had a low to borderline 10-year risk of ASCVD, but the 15-year risk was significantly higher for women with EM versus those without EM. When CAC ≥ 1, the incidence of ASCVD was similar for women with and without EM. These findings support the use of CAC to help improve ASCVD risk stratification in women with EM. Condensed abstract: This study investigated the association between coronary artery calcium (CAC) and incident atherosclerotic cardiovascular disease (ASCVD) in postmenopausal women with and without early menopause (EM). We found that >50% of women had CAC = 0 and an associated low-to-borderline 10-year cumulative incidence of ASCVD. However, the risk for ASCVD was significantly higher for women with EM after 15-years follow-up. Additional research is needed to better understand the differences in long-term ASCVD risk between women with and without EM who have CAC = 0.

Study objectives: The objectives of this study were to identify independent predictors for moderate/accentuated coronary artery calcium (CAC) score and compare patients who self-referred for CAC Computed Tomography (CT) testing to those who were provider-referred. Design: Patients underwent CAC between January to July 2019. The analysis was divided into self-referred patients influenced by a CAC community campaign who identified themselves as having cardiovascular risk factors compared to provider-referred intermediate-risk patients who were asymptomatic. SAS version 9.4 (SAS Institute, Inc., Cary, NC) was used for all analyses. Setting: Seven southwest Ohio hospitals from a single network. Participants: 2124 adult patients who received CAC CT (163 self and 1961 provider-referred). Interventions: CAC CT. Main outcome measures: Demographics, risk factors, lab values, prescriptions, and referral status were used to compare CAC score differences between self- and provider-referred patients. Results: For 2124 patients, three predictors for moderate/accentuated CAC score remained significant after multiple logistic regression: CKD (OR 0.24, CI 0.008–0.68, p

Background: Coronary artery calcifications (CAC) is a strong predictor of cardiovascular disease (CVD), which can be automatically quantified on routine breast radiotherapy planning computed tomography (CT) scans. Around 8% of patients have (very) high CAC scores and corresponding increased risks of CVD. Aim: This study explores whether, how, and under what conditions women with breast cancer want to be informed about their CAC-based CVD risk. Methods: A cross-sectional survey study was conducted in a random sample of UMBRELLA, a prospective breast cancer cohort. Participants (n = 79) filled out a questionnaire about their knowledge on the CVD risk following breast cancer, their interest in being informed about their CVD risk based on CAC score, and preferences on how they would want to receive this information. Results: Most participants (66%) were not aware that the presence of CAC indicates an increased CVD risk. Participants indicated that they were not or only slightly aware of the risk of treatment-induced cardiotoxicity (48%), and that the risk of cardiotoxicity was higher in patients with pre-existing CVD risk factors (82%). The vast majority (90%) indicated that they want to be informed about in increased CAC-based CVD risk. Conclusions: The majority of patients with breast cancer wants to be informed about their CAC-based CVD risk. With the majority of patients with breast cancer undergoing radiotherapy, and with low cost and automated options for accurate CAC measurement in planning CT scans, it is important to develop strategies to manage patients with an increased CAC-based risk of CVD.

The mucosal barrier is crucial for intestinal homeostasis, and goblet cells are essential for maintaining the mucosal barrier integrity. The proviral integration site for Moloney murine leukemia virus-1 (PIM1) kinase regulates multiple cellular functions, but its role in intestinal homeostasis during colitis is unknown. Here, we demonstrate that PIM1 is prominently elevated in the colonic epithelia of both ulcerative colitis patients and murine models, in the presence of intestinal microbiota. Epithelial PIM1 leads to decreased goblet cells, thus impairing resistance to colitis and colitis-associated colorectal cancer (CAC) in mice. Mechanistically, PIM1 modulates goblet cell differentiation through the Wnt and Notch signaling pathways. Interestingly, PIM1 interacts with histone deacetylase 2 (HDAC2) and downregulates its level via phosphorylation, thereby altering the epigenetic profiles of Wnt signaling pathway genes. Collectively, these findings investigate the unknown function of the PIM1-HDAC2 axis in goblet cell differentiation and ulcerative colitis/CAC pathogenesis, which points to the potential for PIM1-targeted therapies of ulcerative colitis and CAC., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Introduction: Skin-sparing mastectomy (SSM) entails complete removal of the breast tissue and the nipple and areola complex (NAC) with preservation of as much of the overlying skin as possible. The preservation of the natural skin envelope during SSM improves the aesthetic outcome of immediate breast reconstruction, but the lack of NAC determines that the reconstructed breast remains anatomically incomplete with not always satisfactory final results. For this purpose, the aim of the present study was to investigate and evaluate the impact of nipple reconstruction after skin sparing and skin reducing mastectomy on the patients' perception and intimate life., Materials and Method: This was a comparative single-center prospective study that involved 42 patients underwent NAC reconstruction after SSM. A pre- and postoperative quality-of-life and psychological questionnaires Breast-Q questionnaire (Breast Conserving therapy module) were given to all the patients before the surgery and 6 months after. The statistical analysis with chi-square test was performed., Results: After 6 months a prevalence of patients reported to be very satisfied in regard to shape, appearance, naturalness, projection, position and symmetry. The study shows an overall improvement in all the psychological items analyzed with statistically significant difference regarding: "patient's satisfaction," "self-confidence," "appearance of the breast.", Conclusion: The authors believe that the NAC reconstruction has useful functional and aesthetic results particularly appreciated by patients who feel demoralized after breast demolition surgery., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Coronary artery calcium (CAC), thoracic aorta calcification (TAC), non-alcoholic fatty liver disease (NAFLD), and epicardial adipose tissue (EAT) are associated with atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF)., Objectives: We aimed to determine whether these cardiometabolic and atherosclerotic risk factors identified by non-contrast chest computed tomography (CT) are associated with HF hospitalizations in patients with LDL-C≥ 190 mg/dL., Methods: We conducted a retrospective cohort analysis of patients with LDL-C ≥190 mg/dL, aged ≥40 years without established ASCVD or HF, who had a non-contrast chest CT within 3 years of LDL-C measurement. Ordinal CAC, ordinal TAC, EAT, and NAFLD were measured. Kaplan-Meier curves and multivariable Cox regression models were built to ascertain the association with HF hospitalization., Results: We included 762 patients with median age 60 (53-68) years, 68% (n=520) female, and median LDL-C level of 203 (194-216) mg/dL. Patients were followed for 4.7 (interquartile range 2.75-6.16) years, and 107 (14%) had a HF hospitalization. Overall, 355 (47%) patients had CAC=0, 210 (28%) had TAC=0, 116 (15%) had NAFLD, and median EAT was 79 mL (49-114). Moderate-Severe CAC (log-rank p<0.001) and TAC (log-rank p=0.006) groups were associated with increased HF hospitalizations. This association persisted when considering myocardial infarction (MI) as a competing risk. NAFLD and EAT volume were not associated with HF., Conclusions: In patients without established ASCVD and LDL-C≥190 mg/dL, CAC was independently associated with increased HF hospitalizations while TAC, NAFLD, and EAT were not., (Copyright © 2024. Published by Elsevier Inc.)

Intestinal immune homeostasis is preserved by commensal bacteria interacting with the host to generate a balanced array of cytokines that are essential for wound repair and for combatting infection. Inflammatory bowel disease (IBD), which can lead to colitis-associated cancer (CAC), is thought to involve chronic microbial irritation following a breach of the mucosal intestinal epithelium. However, the innate immune pathways responsible for regulating these inflammatory processes remain to be fully clarified. Here, we show that commensal bacteria influence STING signaling predominantly in mononuclear phagocytes to produce both pro-inflammatory cytokines as well as anti-inflammatory IL-10. Enterocolitis, manifested through loss of IL-10, was completely abrogated in the absence of STING. Intestinal inflammation was less severe in the absence of cGAS, possibly suggesting a role for cyclic dinucleotides (CDNs) indirectly regulating STING signaling. Our data shed insight into the causes of inflammation and provide a potential therapeutic target for prevention of IBD.

Aims: Studies have indicated inconsistent results regarding the association between plasma levels of Lipoprotein(a) [Lp(a)] and coronary artery calcification (CAC). We performed a systematic review and meta-analysis to investigate the association between elevated levels of Lp(a) and risk of CAC in populations free of cardiovascular disease (CVD) symptoms., Data Synthesis: PubMed, Web of Science, Embase, and Scopus were searched up to July 2022 and the methodological quality was assessed using Newcastle-Ottawa Scale (NOS) scale. Random-effects meta-analysis was used to estimate pooled odds ratio (OR) and 95% confidence interval. Out of 298 studies, data from 8 cross-sectional (n = 18,668) and 4 cohort (n = 15,355) studies were used in meta-analysis. Cohort studies demonstrated a positive significant association between Lp(a) and CAC, so that individuals with Lp(a)≥30-50 exposed to about 60% risk of CAC incidence compared to those with lower Lp(a) concentrations in asymptomatic CVD subjects (OR, 1.58; 95% CI, 1.38-1.80; l 2 , 0.0%; P, 0.483); Subgroup analysis showed that a cut-off level for Lp(a) measurement could not statistically affect the association, but race significantly affected the relationship between Lp(a) and CAC (OR,1.60; 95% CI, 1.41-1.81). Analyses also revealed that both men and women with higher Lp(a) concentrations are at the same risk for increased CAC., Conclusions: Blood Lp(a) level was significantly associated with CAC incidence in asymptomatic populations with CVD, indicating that measuring Lp(a) may be a useful biomarker for diagnosing subclinical atherosclerosis in individuals at higher risk of CAC score., Prospero Registration Number: CRD42022350297., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Treatment of environmental media contaminated with per- and polyfluoroalkyl substances (PFAS) is crucial to mitigate mounting health risks associated with exposure. Colloidal activated carbon (CAC) has shown promise in treating contaminated soils, but understanding the interaction among PFAS during sorption is necessary for optimal remediation. This study investigated the extent to which PFAS of varying chain lengths and functional groups compete for sorption to CAC. Batch tests were conducted with natural soil and spiked water, using CAC at 0.2% w/w to remove seven PFAS with individual starting concentrations up to 0.05 mmol L -1 . PFAS sorption to CAC was evaluated in three systems: a composite mixture of all studied compounds, a binary-solute system, and a single-solute system. The sorption experiments exhibited strong PFAS affinity to CAC, with removal rates between 41% and 100%, and solid/liquid partition coefficients (K d ) between 10 and 10 4 L kg -1 . Differences were noticed among the various spiking mixtures, based on perfluorocarbon chain length, functional group, and the starting PFAS concentrations. Competition effects were detected when PFAS were in a multi-solute system, with an average 10% drop in removal, which can evidently become more relevant at higher concentrations, due to the observed non-linearity of the sorption process. The PFAS most vulnerable to competition effects in multi-solute systems were the short-chain perfluoropentanoic acid (PFPeA) and perfluorobutane sulfonic acid (PFBS), with an up to 25% reduction in removal. In bi-solute systems, perfluorooctane sulfonamide (FOSA) dominated over its ionisable counterparts, i.e. perfluorooctane sulfonic acid (PFOS) and perfluorononanoic acid (PFNA), indicating the importance of hydrophobic effects or layer formation in the sorption process. These results underscore the importance of considering competition in PFAS sorption processes when designing and implementing remediation techniques for PFAS-contaminated media., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Subclinical coronary artery calcification (CAC) is a risk factor for adverse cardiovascular events, but studies investigating its association with outcomes in hospitalized patients with COVID-19 are limited., Methods: This was a retrospective study of 457 patients without history of clinical coronary artery disease (CAD) who underwent chest CT imaging during COVID-19 hospitalization at MCW/Froedtert-affiliated hospitals from July 1, 2020 to July 1, 2021. Visually estimated CAC (yes/no) and CAC burden (none/mild/moderate/severe) were recorded from radiology reports. Unadjusted and adjusted regression models were used to assess associations between CAC and hospital length of stay (LOS), ICU admission, mechanical ventilation, and mortality., Results: The mean age was 63.1 ± 15.3 years. Presence of CAC was associated with mechanical ventilation (p = 0.01), ICU admission (p = 0.02), in-hospital or 30-day mortality (p < 0.01), and hospital LOS (p < 0.001). Compared to no CAC, hospital LOS was increased for mild (p = 0.01) and severe CAC (p = 0.02) after adjustment for covariates. Severe CAC was also associated with increased ICU admission (OR 3.97; p = 0.002) and mechanical ventilation (OR 3.08; p = 0.03) after adjustment. In unadjusted analysis, in-hospital or 30-day mortality increased with magnitude of CAC severity, with HR 2.43 (p = 0.003) for mild and HR 3.70 (p = 0.002) for severe CAC. However, associations with mortality were not significant after adjustment., Conclusions: CAC is associated with increased ICU admission, mechanical ventilation, hospital LOS, and in-hospital or 30-day mortality for patients hospitalized with COVID-19. Patients with severe CAC, and without clinical history of CAD, represent a high-risk population for morbidity and mortality., Competing Interests: None., (© 2023 The Authors.)

Background: Machine learning (ML) models of risk prediction with coronary artery calcium (CAC) and CAC characteristics exhibit high performance, but are not inherently interpretable., Objectives: To determine the direction and magnitude of impact of CAC characteristics on 10-year all-cause mortality (ACM) with explainable ML., Methods: We analyzed asymptomatic subjects in the CAC consortium. We trained ML models on 80% and tested on 20% of the data with XGBoost, using clinical characteristics ​+ ​CAC (ML 1) and additional CAC characteristics of CAC density and number of calcified vessels (ML 2). We applied SHAP, an explainable ML tool, to explore the relationship of CAC and CAC characteristics with 10-year all-cause and CV mortality., Results: 2376 deaths occurred among 63,215 patients [68% male, median age 54 (IQR 47-61), CAC 3 (IQR 0-94.3)]. ML2 was similar to ML1 to predict all-cause mortality (Area Under the Curve (AUC) 0.819 vs 0.821, p ​= ​0.23), but superior for CV mortality (0.847 vs 0.845, p ​= ​0.03). Low CAC density increased mortality impact, particularly ≤0.75. Very low CAC density ≤0.75 was present in only 4.3% of the patients with measurable density, and 75% occurred in CAC1-100. The number of diseased vessels did not increase mortality overall when simultaneously accounting for CAC and CAC density., Conclusion: CAC density contributes to mortality risk primarily when it is very low ≤0.75, which is primarily observed in CAC 1-100. CAC and CAC density are more important for mortality prediction than the number of diseased vessels, and improve prediction of CV but not all-cause mortality. Explainable ML techniques are useful to describe granular relationships in otherwise opaque prediction models., Competing Interests: Declaration of competing interest Dr. Lin received a research grant from GE. All other authors have no disclosures., (Copyright © 2022 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Severe acute respiratory disease coronavirus 2 (SARS-COV-2) first emerged in Wuhan, China, in December 2019 and has caused a global pandemic of a scale unprecedented in the modern era. People infected with SARS-CoV-2 can be asymptomatic, moderate symptomatic or develop severe COVID-19. Other than the typical acute respiratory distress syndrome (ARDS), patients with moderate or severe COVID-19 also develop a distinctive systemic coagulopathy, known as COVID-19-associated coagulopathy (CAC), which is different from sepsis-related forms of disseminated intravascular coagulation (DIC). Endotheliopathy or endotheliitis are other unique features of CAC. The endothelial cell perturbation can further increase the risk of thrombotic events in COVID-19 patients. In this review, we will summarize the current knowledge on COVID-19 coagulopathy and the possible mechanisms for the condition. We also discuss the results of clinical trials testing methods for mitigating thrombosis events in COVID-19 patients., Competing Interests: Declaration of competing interest Authors declare that they have no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background and Aims: Coronary artery calcium (CAC) and carotid plaque are markers of atherosclerosis and predict future coronary heart disease (CHD) events. The aim of this study was to investigate associations between CAC and carotid plaque in asymptomatic individuals, also in relation to predicted CHD-risk and incident events. A secondary aim was to compare predictive value between CAC, carotid plaque, and total carotid plaque area (TPA) as predictors for future CHD-events., Methods: The REFINE-Reykjavik study is prospective and population-based with CAC-scoring and carotid plaque ultrasound assessment, both presence and area. A total of 948 individuals without clinical CHD were included in the study. CAC scores were categorized into 0,1-100,101-300 and > 300, and carotid plaque into none, minimal and significant. Three models were applied adjusted for age, sex, and each of the Framingham risk score (FRS), local CHD risk score and established CHD risk factors., Results: Combined carotid plaque- and CAC-presence was highly prevalent, 69.5% for males and 41.7% for females (54.5% overall). TPA outperformed base models in CHD prediction, resulting in statistically significant area under the receiver operator characteristic curve (AUC) increase ranging from 0.02 to 0.05. Most CHD-events in females occurred in individuals classified as low-risk with respect to traditional risk factors but with a gradient in observed risk across carotid plaque categories., Conclusions: Carotid plaque was strongly associated with the presence and extent of CAC in asymptomatic individuals in a population-based cohort. Carotid plaque predicts incident CHD events over risk scores and may be useful for refined risk prediction in females., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Study Objectives: The objectives of this study were to identify independent predictors for moderate/accentuated coronary artery calcium (CAC) score and compare patients who self-referred for CAC Computed Tomography (CT) testing to those who were provider-referred., Design: Patients underwent CAC between January to July 2019. The analysis was divided into self-referred patients influenced by a CAC community campaign who identified themselves as having cardiovascular risk factors compared to provider-referred intermediate-risk patients who were asymptomatic. SAS version 9.4 (SAS Institute, Inc., Cary, NC) was used for all analyses., Setting: Seven southwest Ohio hospitals from a single network., Participants: 2124 adult patients who received CAC CT (163 self and 1961 provider-referred)., Interventions: CAC CT., Main Outcome Measures: Demographics, risk factors, lab values, prescriptions, and referral status were used to compare CAC score differences between self- and provider-referred patients., Results: For 2124 patients, three predictors for moderate/accentuated CAC score remained significant after multiple logistic regression: CKD (OR 0.24, CI 0.008-0.68, p  < 0.05), COPD (OR 0.39, CI 0.19-0.80, p  < 0.05), and CAD (OR 0.46, CI 0.22-0.98, p < 0.05). There were four differences between referred groups: history of PVD (OR 0.21, CI 0.05-0.86, p  < 0.05), higher triglyceride (OR 1.004, CI 1.00-1.01, p  < 0.05), higher LDL levels (OR 0.991, CI 0.98-1.00, p < 0.05), and beta blocker prescription (OR 4.38, CI 1.49-12.85, p < 0.05) in self-referred patients., Conclusions: CAC CT testing is associated with independent risk predictors and can be used to clarify cardiovascular risk in self- and provider-referred patients with statistical similarity. Patients reliably self-refer for CAC CT when risk is present during a community initiative. Such initiatives may have a preventive benefit and lead to earlier pursuit and optimization of anti-lipid therapies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Objective: To evaluate the influence of coronary artery dominance on observed coronary artery calcification burden in outpatients presenting for coronary computed tomography angiography (CCTA)., Methods: A 12-month retrospective review was performed of all CCTAs at a single institution. Coronary arterial dominance, Agatston score and presence or absence of cardiovascular risk factors including hypertension (HTN), hyperlipidemia (HLD), diabetes and smoking were recorded. Dominance groups were compared in terms of calcium score adjusted for covariates using analysis of covariance based on ranks. Only covariates observed to be significant independent predictors of the relevant outcome were included in each analysis. All statistical tests were conducted at the two-sided 5% significance level., Results: 1223 individuals, 618 women and 605 men were included, mean age 60 years (24-93 years). Right coronary dominance was observed in 91.7% (n = 1109), left dominance in 8% (n = 98), and codominance in 1.3% (n = 16). The distribution of patients among Agatston score severity categories significantly differed between codominant and left (p = 0.008), and codominant and right (p = 0.022) groups, with higher prevalence of either zero or severe CAC in the codominant patients. There was no significant difference in Agatston score between dominance groups. In the subset of individuals with coronary artery calcification, Agatston score was significantly higher in codominant versus left dominant patients (mean Agatston score 595 ± 520 vs. mean 289 ± 607, respectively; p = 0.049), with a trend towards higher scores in comparison to the right-dominant group (p = 0.093). Significance was not maintained upon adjustment for covariates., Conclusions: While the distribution of Agatston score severity categories differed in codominant versus right- or left-dominant patients, there was no significant difference in Agatston score based on coronary dominance pattern in our cohort. Reporting and inclusion of codominant subsets in larger investigations may elucidate whether codominant anatomy is associated with differing risk., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Chronic kidney disease (CKD) is a risk factor for atherosclerotic cardiovascular disease (ASCVD). American cardiovascular societies consider CKD a risk-enhancing factor that supports statin therapy in intermediate-risk patients aged 40-75 years. In contrast, European cardiovascular societies recommend statins for all middle-aged adults with CKD. The Kidney Disease: Improving Global Outcomes lipid management guideline for CKD recommends statin therapy for all patients with CKD >50 years. Clinical implications for these differences have not been examined., Objective: This study examines CKD prevalence and statin eligibility in non-ASCVD adults, representative of the US population, at 3 levels of 10-year risk of ASCVD estimated by pooled cohort equations., Methods: National Health and Nutrition Examination Surveys 1999-2016 weighted data were evaluated for CKD defined as estimated glomerular filtration rate < 60 mL/min/1.73 m 2 . Overall prevalence of low, intermediate, and high 10-year risk for ASCVD was determined., Results: A total of 92.5% of all participants had estimated glomerular filtration rate ≥ 60 mL/min/1.73 m 2 ; 7.5% (confidence interval 6.9%, 8.1%) had CKD. Among participants with CKD, 46.3% had 10-year risk for ASCVD <7.5% (low risk); 31.7% had intermediate risk (7.5-< 20%), and 22.0% had high risk (≥20%). In participants with CKD, 62.5% were women. A total of 19.6% of all participants with CKD had diabetes. A total of 46.3% of participants with CKD at intermediate or high risk reported taking cholesterol-lowering drugs., Conclusion: A total of 46.3% of patients with CKD aged 40-75 years had 10-year risk <7.5% (low risk) and hence were statin eligible by European and Kidney Disease: Improving Global Outcomes (>50 years) guidelines. US cardiovascular guidelines limit statin eligibility to intermediate- and high-risk CKD. Statin eligibility in lower-risk patients may be best determined by measuring coronary artery calcium., (Copyright © 2020 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background: Genetic risk scores (GRSs) have been associated with CHD events and coronary artery calcium (CAC). We sought to evaluate the ability of a GRS to improve CAC as a screening test., Methods: Using the results of the most recent genome-wide association studies, we calculated a GRS in 6660 individuals from the Multi-Ethnic Study of Atherosclerosis and used it to determine the optimal age for an individual to undergo CAC screening., Results: This 157-SNP GRS was predictive of non-zero CAC in individuals aged 44-54 and improved the positive yield of CAC as a screening test in this age group. The GRS was predictive of CAC in the entire multi-ethnic cohort and in each self-identified ethnic group (European American, Chinese American, African American, and Hispanic American) assessed individually. Given a specified target yield rate of non-zero CAC, an equation was derived to calculate an individual's optimal age to undergo CAC screening. In addition, a "direct-to-consumer" GRS consisting of only risk SNPs or their proxies that are directly genotyped on the 23andMe v5 chip (102-SNP GRS) was assessed in the European American population and was predictive of non-zero CAC in younger individuals., Conclusion: A GRS is associated with non-zero CAC in a multi-ethnic cohort and can be used to calculate the age of a person's first calcium scan, given a target threshold for CAC discovery. Furthermore, an inexpensive and widely available "direct-to-consumer" GRS was found to be a viable option to calculate the optimal age for CAC screening., (Copyright © 2019 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

This review evaluates the cost-effectiveness of using coronary artery calcium (CAC) to guide long-term statin therapy compared with treating all patients eligible for statins according to 2013 American College of Cardiology/American Heart Association cholesterol management guidelines for atherosclerotic cardiovascular disease. The authors used a microsimulation model to compare costs and effectiveness from a societal perspective over a lifetime horizon. Both strategies resulted in similar costs and quality-adjusted life years (QALYs). CAC resulted in increased costs (+$81) and near-equal QALY (+0.01) for an incremental cost-effectiveness ratio of $8,100/QALY compared with the treat-all strategy. For 10,000 patients, the treat-all strategy would theoretically avert 21 atherosclerotic cardiovascular disease events, but would add 47,294 person-years of statins. With CAC costs <$100, and higher cost and/or disutility associated with statin therapy, CAC strategy was favored. These findings suggest the economic value of both approaches were similar. Clinicians should account for individual preferences in context of shared decision making when choosing the most appropriate strategy to guide statin decisions., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Endogenous recruitment of circulating angiogenic cells (CACs) is an emerging strategy to induce angiogenesis within a defect site, and multiple recent strategies have deployed soluble protein releasing biomaterials for this purpose. However, the way in which the design of biomaterials affects CAC recruitment and invasion are poorly understood. Here we used an enhanced-throughput cell invasion assay to systematically examine the effects of biomaterial design on CAC recruitment. The screens co-optimized hydrogel presentation of a stromal-derived factor-1α (SDF-1α) gradient, hydrogel degradability, and hydrogel stiffness for maximal CAC invasion. We also examined the specificity of this invasion by assessing dermal fibroblast, mesenchymal stem cell, and lymphocyte invasion individually and in co-culture with CACs to identify hydrogels specific to CAC invasion. These screens suggested a subset of MMP-degradable hydrogels presenting a specific range of SDF-1α gradient slopes that induced specific invasion of CACs, and we posit that the design parameters of this subset of hydrogels may serve as instructive templates for the future design of biomaterials to specifically recruit CACs. We also posit that this design concept may be applied more broadly in that it may be possible to utilize these specific subsets of biomaterials as "filters" to control which types of cell populations invade into and populate the biomaterial., Statement of Significance: The recruitment of specific cell types for cell-based therapies in vivo is of great interest to the regenerative medicine community. Circulating angiogenic cells (CACs), CD133+ cells derived from the blood stream, are of particular interest for induction of angiogenesis in ischemic tissues, and recent studies utilizing soluble-factor releasing biomaterials to recruit these cells in vivo show great promise. However, these studies are largely "proof of concept" and are not systematic in nature. Thus, little is currently known about how biomaterial design affects the recruitment of CACs. In the present work, we use a high throughput cell invasion screening platform to systematically examine the effects of biomaterial design on circulating angiogenic cell (CAC) recruitment, and we successfully screened 263 conditions at 3 replicates each. Our results identify a particular subset of conditions that robustly recruit CACs. Additionally, we found that these conditions also specifically recruited CACs and excluded the other tested cells types of dermal fibroblasts, mesenchymal stem cells, and lymphocytes. This suggests an intriguing new role for biomaterials as "filters" to control the types of cells that invade and populate that biomaterial., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The photocatalytic activity and the promoting effect of titania (TiO2) by commercial activated carbon (CAC) for removing the pollutant in wastewater were investigated. The TiO2/CAC composite photocatalysts with various ratios of CAC to TiO2 were prepared by sol-gel method. The catalyst was characterized by X-ray diffraction (XRD), high resolution scanning electron microscope (HR-SEM), energy dispersive spectra (EDS), diffuse reflectance spectra (DRS), photoluminescence spectra (PL), X-ray photoelectron spectroscopy (XPS) and Brunauer-Emmett-Teller (BET) surface area measurement methods. The photocatalytic activity of TiO2/CAC was investigated for the degradation of Sunset Yellow (SY) in aqueous solution using UV-A light. The TiO2/CAC is found to be more efficient than prepared TiO2 and TiO2-P25 at pH 7 for the mineralization of SY. The synergism between TiO2 and CAC may increase the catalytic activity. The effects of operational parameters such as the amount of photocatalyst, dye concentration and initial pH on photo mineralization of SY have been analyzed. The mineralization of SY has been confirmed by COD measurements. The catalyst is found to be reusable., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to examine whether magnesium intake is associated with coronary artery calcification (CAC) and abdominal aortic calcification (AAC)., Background: Animal and cell studies suggest that magnesium may prevent calcification within atherosclerotic plaques underlying cardiovascular disease. Little is known about the association of magnesium intake and atherosclerotic calcification in humans., Methods: We examined cross-sectional associations of self-reported total (dietary and supplemental) magnesium intake estimated by food frequency questionnaire with CAC and AAC in participants of the Framingham Heart Study who were free of cardiovascular disease and underwent Multi-Detector Computed Tomography (MDCT) of the heart and abdomen (n = 2,695; age: 53 ± 11 years), using multivariate-adjusted Tobit regression. CAC and AAC were quantified using modified Agatston scores (AS). Models were adjusted for age, sex, body mass index, smoking status, systolic blood pressure, fasting insulin, total-to-high-density lipoprotein cholesterol ratio, use of hormone replacement therapy (women only), menopausal status (women only), treatment for hyperlipidemia, hypertension, cardiovascular disease prevention, or diabetes, as well as self-reported intake of calcium, vitamins D and K, saturated fat, fiber, alcohol, and energy. Secondary analyses included logistic regressions of CAC and AAC outcomes as cut-points (AS >0 and AS ≥90th percentile for age and sex), as well as sex-stratified analyses., Results: In fully adjusted models, a 50-mg/day increment in self-reported total magnesium intake was associated with 22% lower CAC (p < 0.001) and 12% lower AAC (p = 0.07). Consistent with these observations, the odds of having any CAC were 58% lower (p trend: <0.001) and any AAC were 34% lower (p trend: 0.01), in those with the highest compared to those with the lowest magnesium intake. Stronger inverse associations were observed in women than in men., Conclusions: In community-dwelling participants free of cardiovascular disease, self-reported magnesium intake was inversely associated with arterial calcification, which may play a contributing role in magnesium's protective associations in stroke and fatal coronary heart disease., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The regions of Durham and York in Ontario, Canada have partnered to construct an energy-from-waste thermal treatment facility as part of a long term strategy for the management of their municipal solid waste. This paper presents the results of a comprehensive human health risk assessment for this facility. This assessment was based on extensive sampling of baseline environmental conditions (e.g., collection and analysis of air, soil, water, and biota samples) as well as detailed site specific modeling to predict facility-related emissions of 87 identified contaminants of potential concern. Emissions were estimated for both the approved initial operating design capacity of the facility (140,000 tonnes per year) and for the maximum design capacity (400,000 tonnes per year). For the 140,000 tonnes per year scenario, this assessment indicated that facility-related emissions are unlikely to cause adverse health risks to local residents, farmers, or other receptors (e.g., recreational users). For the 400,000 tonnes per year scenarios, slightly elevated risks were noted with respect to inhalation (hydrogen chloride) and infant consumption of breast milk (dioxins and furans), but only during predicted 'upset conditions' (i.e. facility start-up, shutdown, and loss of air pollution control) that represent unusual and/or transient occurrences. However, current provincial regulations require that additional environmental screening would be mandatory prior to expansion of the facility beyond the initial approved capacity (140,000 tonnes per year). Therefore, the potential risks due to upset conditions for the 400,000 tonnes per year scenario should be more closely investigated if future expansion is pursued., (© 2013.)

Objectives: Statins have been shown to reduce plaque progression using data on intravascular ultrasound, carotid intima-media thickness and coronary artery calcium scans. However, there is little data on effects of statins on plaque progression using Coronary CTA. The objective is to evaluate the effect of statin therapy on plaque progression using serial Coronary CTA (CCTA)., Methods: The study included 100 consecutive patients who underwent serial Coronary CTA (mean follow up: 406 ± 92 days) for evaluation of CAD without known prior heart disease or revascularization. We performed volumetric assessment of low attenuation plaque (LAP < 30 Hounsfield units), non-calcified (NCP) and calcified plaque volumes at baseline and follow up scans for vessels >2 mm in diameter. Patients who received statins were compared to those that did not., Results: Total plaque progression was significantly reduced among statin user compared to non-statin users (-33.3 mm(3) ± 90.5 vs. 31.0 mm(3) ± 84.5, p = 0.0006). Statin users had significantly reduced progression of NCP volume (-47.7 mm(3) ± 71.9 vs. 13.8 mm(3) ± 76.6, p < 0.001) and significantly reduced progression of LAP volume (-12.2 mm(3) ± 19.2 vs. 5.9 mm(3) ± 23.1, p < 0.0001). When we compared for remodeling index, no statistical difference was found between the two groups (p = 0.25) and a non-significant trend toward calcium progression (29.3 mm(3) ± 67.9 vs. 10.0 mm(3) ± 53.2, p = 0.133). After adjustment for cardiovascular risk factors, mean plaque volume difference between statin and non-statin users was statistically significant for both LAP and NCP volumes (-18.1, 95% CI: -26.4, -9.8 for LAP; -101.7, 95% CI: -162.1, -41.4 for NCP; p < 0.001) respectively., Conclusion: Statin therapy resulted in significantly lower progression of LAP and NCP plaques compared to non-statin users., (Copyright © 2013. Published by Elsevier Ireland Ltd.)

Molecular imaging seeks to unravel critical molecular and cellular events in living subjects by providing complementary biological information to current structural clinical imaging modalities. In recent years, molecular imaging efforts have marched forward into the clinical cardiovascular arena, and are now actively illuminating new biology in a broad range of conditions, including atherosclerosis, myocardial infarction, thrombosis, vasculitis, aneurysm, cardiomyopathy, and valvular disease. Development of novel molecular imaging reporters is occurring for many clinical cardiovascular imaging modalities (positron emission tomography, single-photon emission computed tomography, magnetic resonance imaging), as well as in translational platforms such as intravascular fluorescence imaging. The ability to image, track, and quantify molecular biomarkers in organs not routinely amenable to biopsy (e.g., the heart and vasculature) open new clinical opportunities to tailor therapeutics based on a cardiovascular disease molecular profile. In addition, molecular imaging is playing an increasing role in atherosclerosis drug development in phase II clinical trials. Here, we present state-of-the-art clinical cardiovascular molecular imaging strategies, and explore promising translational approaches positioned for clinical testing in the near term., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to determine whether arterial inflammation measured by (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) improves prediction of cardiovascular disease (CVD) beyond traditional risk factors., Background: It is unknown whether arterial (18)F-FDG uptake measured with routine PET imaging provides incremental value for predicting CVD events beyond Framingham risk score (FRS)., Methods: We consecutively identified 513 individuals from 6,088 patients who underwent (18)F-FDG-PET and computed tomography (CT) imaging at Massachusetts General Hospital between 2005 and 2008 and who met additional inclusion criteria: ≥30 years of age, no prior CVD, and free of cancer. CVD events were independently adjudicated, while blinded to clinical data, using medical records to determine incident stroke, transient ischemic attack, acute coronary syndrome, revascularization, new-onset angina, peripheral arterial disease, heart failure, or CVD death. FDG uptake was measured in the ascending aorta (as target-to-background-ratio [TBR]), while blinded to clinical data., Results: During follow-up (median 4.2 years), 44 participants developed CVD (2 per 100 person-years at risk). TBR strongly predicted subsequent CVD independent of traditional risk factors (hazard ratio: 4.71; 95% confidence interval [CI]: 1.98 to 11.2; p < 0.001) and (hazard ratio: 4.13; 95% CI: 1.59 to 10.76; p = 0.004) after further adjustment for coronary calcium score. Addition of arterial PET measurement to FRS scores improved the C-statistic (mean ± standard error 0.62 ± 0.03 vs. 0.66 ± 0.03). Further, incorporation of TBR into a model with FRS variables resulted in an integrated discrimination of 5% (95% CI: 0.36 to 9.87). Net reclassification improvements were 27.48% (95% CI: 16.27 to 39.92) and 22.3% (95% CI: 11.54 to 35.42) for the 10% and 6% intermediate-risk cut points, respectively. Moreover, TBR was inversely associated with the timing of CVD (beta -0.096; p < 0.0001)., Conclusions: Arterial FDG uptake, measured from routinely obtained PET/CT images, substantially improved incident CVD prediction beyond FRS among individuals undergoing cancer surveillance and provided information on the potential timing of such events., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Whether lipoprotein (a) [Lp(a)] concentration is associated with metabolic syndrome (MetS) and pre-clinical atherosclerosis in different ethnic groups is uncertain. The association between Lp(a), MetS and a measure of pre-clinical atherosclerosis was studied in a large Asian cohort., Methods and Results: Data were analyzed from a South Korean occupational cohort who underwent a cardiac computed tomography (CT) estimation of CAC score and measurements of cardiovascular risk factors (n = 14,583 people). The key exposure was an Lp(a) concentration in the top quartile (>38.64 mg/dL)) with a CAC score >0 as the outcome variable and measure of pre-clinical atherosclerosis. Logistic regression was used to describe the associations. 1462 participants had a CAC score >0. In the lowest Lp(a) quartile (<11.29 mg/dL), 25.8% had MetS, compared with 16.1% in the highest Lp(a) quartile (>38.64 mg/dL (p < 0.001). MetS, and component features, were inversely related to Lp(a) concentration (all p < 0.0001). In the highest Lp(a) quartile group, there was an association between Lp(a) and CAC score >0 in men (OR 1.21[1.05, 1.40], p = 0.008), and women (OR 1.62[1.03, 2.55], p = 0.038), after adjustment for age, sex, lipid lowering therapy, and multiple cardiovascular risk factors. There was no evidence of an interaction between highest quartile Lp(a) and either high LDLc (>147 mg/dL) (p = 0.99), or MetS (p = 0.84) on the association with CAC score >0., Conclusion: Lp(a) levels are inversely related to MetS and its components. There was a robust association between Lp(a) concentration >38.6 mg/dL and marker of early atherosclerosis in both men and women, regardless of LDLc, level MetS or other cardiovascular risk factors., (© 2013 Elsevier B.V. All rights reserved.)

Background: The independent effect of high density lipoprotein cholesterol (HDL-C) concentration to confer cardiovascular disease protection has been questioned. We investigated whether the inverse association between HDL-C concentration and a measure of preclinical atherosclerosis was modified by other risk factors., Methods: Cross-sectional data were analysed from an occupational cohort of 12,031 men who had measurements of cardiovascular risk factors and a cardiac computed tomography (CT) estimation of coronary artery calcium (CAC) score, a measure of pre-clinical atherosclerosis. Logistic regression was used to describe associations between both HDL-C and Apo-A-I concentrations and their ratio as exposures, and CAC scores > 0, ≥ 20 and ≥ 100, as outcomes., Results: 1351 (11.2%), 665 (5.5%) and 230 (1.9%) of participants had a CAC score > 0, ≥ 20 and ≥ 100, respectively. Adjusting for age, glucose, triglyceride, LDL-C, systolic blood pressure, waist circumference, prior cerebrovascular accident, prior coronary artery disease, prior hypertension, alcohol consumption, smoking status and exercise, a negative association existed between HDL-C and CAC score. (E.g. odds ratio (OR) for top compared to bottom HDL-C quartile for CAC > 0 = 0.78 [95%CI 0.64, 0.94], p = 0.01). Further adjustment for Apo A-I changed the direction of the association between HDL-C and CAC score > 0 (OR for top compared to bottom quartiles 1.61 [95%CI 1.18, 2.21], p = 0.003). Sensitivity analyses showed that point estimates for ORs were very similar regardless of CAC score threshold (CAC > 0, ≥ 20 and ≥ 100)., Conclusion: Controlling for Apo A-I concentrations changes the inverse direction of relationship between high HDL-C concentration and a measure of pre-clinical atherosclerosis., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Fully supramolecular dendrosomes (FSD) as bi-phase drug delivery systems are reported in this work. For preparation of FSD, amphiphilic linear-dendritic supramolecular systems (ALDSS) have been synthesized by host-guest interactions between hyperbranched polyglycerol having β-cyclodextrin core and bi-chain polycaprolactone (BPCL) with a fluorescine focal point. Self-assembly of ALDSS in aqueous solutions led to FSD. They were able to encapsulate paclitaxel with a high loading capacity. The dendrosome-based drug delivery systems were highly sensitive to pH and temperature. They were stable at 20-37 °C and pH7-8, but dissociated and released drug at temperatures lower than 20 °C or higher than 37 °C and pH lower than 7 quickly. Dissociation of FSD building blocks by temperature or pH resulted in inclusion complexes between the released drugs and polyglycerol as the secondary drug delivery system., From the Clinical Editor: This paper reports on the development of a pH- (below 7) and temperature- (below 20 °C or above 37 °C) sensitive delivery system using supramolecular dendrosomes for more specific delivery and release of drugs using paclitaxel as a model., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to assess the relationship between carotid artery disease by ultrasound and coronary artery disease by coronary computed tomography angiography (CTA) and to identify carotid ultrasound parameters predictive of coronary artery disease., Background: Carotid ultrasound and CTA are noninvasive modalities used to image atherosclerosis. Studies examining the relationship between the 2 tests, however, are lacking., Methods: We performed carotid ultrasound on predominantly nondiabetic subjects referred for CTA. Carotid intima media thickness (IMT) and plaque were assessed and compared with coronary artery calcification and the number of coronary arteries with any evidence of atherosclerosis on CTA., Results: A total of 150 subjects underwent both CTA and carotid ultrasound on the same day. Carotid plaque was present in 71.3% (n = 107), whereas the presence of at least 1 coronary artery with disease on CTA was present in 57.1% (n = 84). Carotid plaque was present in 47.6% (30 of 63) of subjects with a calcium score of 0 and 88.5% (77 of 87) of subjects with a calcium score >0 (p = 0.0001). Similarly carotid plaque was present in 52.4% (33 of 63) of subjects with no CTA evidence of atherosclerosis versus 85.7% (72 of 84) of subjects with any CTA evidence of atherosclerosis (p < 0.0001). Carotid plaque, IMT ≥ 1.5 mm, or averaged mean IMT >0.75 mm were associated with a calcium score >0 (odds ratio: 5.4, p < 0.0001, 2.7, p < 0.001; 2.9, p = 0.011, respectively) and disease in at least 1 vessel on CTA (odds ratio: 2.8, p = 0.03, 2.19, p = 0.073; 2.22, p = 0.058, respectively) independent of age and sex., Conclusions: Carotid plaque and increased carotid IMT are associated with the presence and severity of coronary calcification and disease on CTA in ambulatory subjects., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Inverse correlations of high serum bilirubin with metabolic and cardiovascular disease have been suggested. However, anti-atherogenic effects of bilirubin have not been well-established in terms of the presence of plaques and stenosis identified in coronary computed tomography (CT)., Methods: A cross-sectional study was conducted on 2862 men who were free of cardiovascular disease and underwent coronary CT as part of a routine medical screening examination. Coronary stenotic lesions were considered to be incidences of coronary atherosclerosis, and stenosis was classified as stenosis <50% or ≥50%, according to degree of stenosis., Results: The prevalences of coronary atherosclerosis and stenosis ≥50% in subjects with elevated bilirubin levels (>1.2 mg/dL) were lower than those in subjects with normal bilirubin levels (≤1.2 mg/dL) (19.9% vs. 27.9%, p < 0.001, 8.5% vs. 10.3%, p = 0.044). Bilirubin was inversely associated with total plaques (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.48-0.73 in the 4th quartile vs. 1st quartile) and calcified plaques (OR 0.60, 95% CI 0.49-0.75) in univariate analysis. After adjusting for traditional risk factors, it was found that coronary atherosclerosis (OR 0.73, 95% CI 0.56-0.94 in the 4th quartile vs. 1st quartile) and calcified plaque (OR 0.66, 95% CI 0.53-0.84) were inversely associated with the bilirubin grade in a dose-dependent manner., Conclusions: The serum bilirubin level was inversely associated with coronary atherosclerosis and calcified plaques in a dose-dependent manner. These results suggested that serum bilirubin could be used as a protective biomarker of coronary artery disease., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: We sought to identify the predictors of non-calcified plaque (NCP) burden in patients with low coronary artery calcium (CAC) scores of 1-100., Methods: We studied 920 consecutive patients clinically referred for coronary CT angiography (CCTA) with concomitant CAC scoring. The 276 patients with CAC 1-100 were divided into four groups based on the CAC score: CAC = 0, 1-10, 11-50, and 51-100. Univariate and multivariate linear regression analyses were performed for the demographic, risk factor, and CAC score predictors of number of coronary segments with NCP., Results: Mean age was 55 ± 11 years and 56% were women. Demographics and risk factors failed to identify NCP involvement in univariate models. The lone predictor of NCP burden was the absolute CAC score, which was persistently associated with NCP in multivariable models (CAC 51-100 vs. CAC 1-10, β-coefficient 0.35, p = 0.03)., Conclusions: Absolute CAC score is the lone robust predictor of NCP burden when CAC is 1-100. Risk within this mild coronary calcification group is likely heterogeneous, driven by the absolute CAC score., (© 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: Ankle-brachial index (ABI) screening is recommended for the detection of asymptomatic peripheral arterial disease (PAD) in at-risk populations, including diabetics. A low ABI identifies obstructive lower extremity vascular disease and predicts CVD events and increased mortality. A high ABI represents non-compressible arterial disease (NCAD), and is also associated with increased mortality and vascular events. Our objective is to investigate whether low and high ABI have distinct patterns of association with cardiovascular disease (CVD) risk factors and subclinical atherosclerosis in individuals with type-II diabetes mellitus., Methods: The Penn Diabetes Heart Study (PDHS) is a prospective observational cohort of diabetic individuals without clinically evident CVD. Multivariate logistic and Tobit linear regression were used to compare CVD risk factors and coronary artery (CAC) among 1863 subjects with PAD (ABI ≤ 0.9), NCAD (ABI ≥ 1.4 or non-compressible) or normal ABI (0.91-1.39)., Results: Compared to those with normal ABI, PAD was associated with smoking, obesity, and lower HDL-c; while diabetes duration and reduced renal function were associated with NCAD. Both PAD and NCAD were independently associated with increased CAC compared to those with normal ABI, and these relationships were not attenuated in multiply adjusted models., Conclusion: NCAD bears a distinct relationship to traditional CVD risk factors among diabetics, though like PAD is independently associated with increased CAC. These findings support the recognition of NCAD as a high-risk phenotype and provide additional relevance to ABI screening in diabetics., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)