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Using the Keldysh nonequilibrium Green function method, we theoretically investigate the electron transport properties of a quantum dot coupled to two ferromagnetic electrodes, with inelastic electron-phonon interaction and spin flip scattering present in the quantum dot. It is found that the electron-phonon interaction reduces the current, induces new satellite polaronic peaks in the differential conductance spectrum, and at the same time leads to oscillatory tunneling magnetoresistance effect. Spin flip scattering suppresses the zero-bias conductance peak and splits it into two, with different behaviors for parallel and anti-parallel magnetic configuration of the two electrodes. Consequently, a negative tunneling magnetoresistance effect may occur in the resonant tunneling region, with increasing spin flip scattering rate. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this prospective, randomized study was to evaluate the hemodynamic and analgesic effects of ketamine by comparing it with propofol starting at the induction of anesthesia until the end of sternotomy in patients undergoing coronary artery bypass grafting surgery. INTRODUCTION: Anesthetic induction and maintenance may induce myocardial ischemia in patients with coronary artery disease. A primary goal in the anesthesia of patients undergoing coronary artery bypass grafting surgery is both the attenuation of sympathetic responses to noxious stimuli and the prevention of hypotension. METHODS: Thirty patients undergoing coronary artery bypass grafting surgery were randomized to receive either ketamine 2 mg.kg-1 (Group K) or propofol 0.5 mg.kg-1 (Group P) during induction of anesthesia. Patients also received standardized doses of midazolam, fentanyl, and rocuronium in the induction sequence. The duration of anesthesia from induction to skin incision and sternotomy, as well as the supplemental doses of fentanyl and sevoflurane, were recorded. Heart rate, mean arterial pressure, central venous pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac index, systemic and pulmonary vascular resistance indices, stroke work index, and left and right ventricular stroke work indices were obtained before induction of anesthesia; one minute after induction; one, three, five, and ten minutes after intubation; one minute after skin incision; and at one minute after sternotomy. RESULTS: There were significant changes in the measured and calculated hemodynamic variables when compared to their values before induction. One minute after induction, mean arterial pressure and the systemic vascular resistance index decreased significantly in group P (p

Voluntary, safe and dignified return is one of the durable solutions to forced displacement and, thus, hosting states have the responsibility to provide international protection to refugees until the conditions for voluntary repatriation are met. Premature or forced return that is falling short of international standards would mean a violation of the principle of non-refoulement. Current global governance of forced displacement impeding seeking asylum, delaying resettlement, and facilitating return ends up violating the very founding principles of the international refugee regime while exposing refugees and asylum-seekers to violence and higher risks.

Introduction : This study aimed to investigate the relationship between Med-Diet adherence with sustainable nutrition and environmental footprints in academicians. Methods : The study involved 153 academicians aged 23-64 working in a university in Turkey. Data were collected through a questionnaire including socio-demographic characteristics, anthropometric measurements, Mediterranean Diet Adherence Scale (MEDAS) and Sustainable and Healthy Eating Behaviours Scale (SHEBS). Carbon and water footprints were calculated. Results : All sub-scales of SHEBS were higher in individuals who adhered to Med-Diet than those who did not (p<0.05). The carbon and water footprints of individuals with high adherence to the Med-Diet were lower than those of no adherence (p<0.05). Each 1-point increase in MEDAS score was associated with a 1-point increase in SHEBS score, a 0.15 CO2 eq/kg and a 0.001 m3/year decrease in the amount of carbon and water footprint of food. Conclusion : Higher adherence to the Med-Diet was associated with higher sustainable nutrition behaviours, and lower environmental footprints.

Competing Interests: Disclosures Dr Saguner received educational grants through his institution from Abbott, Bayer Healthcare, Biosense Webster, Biotronik, Boston Scientific, Bristol-Myers Squibb/Pfizer, and Medtronic and speaker/advisory board/consulting fees from Bayer Healthcare, Biotronik, Medtronic, Novartis, Pfizer, StrideBio, and Zoll. The rest of the authors report no conflicts of interest.

Background: There is limited information on the mode of arrhythmia initiation in idiopathic ventricular fibrillation (IVF). A non-pause-dependent mechanism has been suggested to be the rule., Objectives: The aim of this study was to assess the mode and characteristics of initiation of polymorphic ventricular tachycardia (PVT) in patients with short or long-coupled PVT/IVF included in THESIS (THerapy Efficacy in Short or long-coupled idiopathic ventricular fibrillation: an International Survey), a multicenter study involving 287 IVF patients treated with drugs or radiofrequency ablation., Methods: We reviewed the initiation of 410 episodes of ≥1 PVT triplet in 180 patients (58.3% females; age 39.6 ± 13.6 years) with IVF. The incidence of pause-dependency arrhythmia initiation (prolongation by >20 ms of the preceding cycle length) was assessed., Results: Most arrhythmias (n = 295; 72%) occurred during baseline supraventricular rhythm without ambient premature ventricular complexes (PVCs), whereas 106 (25.9%) occurred during baseline rhythm including PVCs. Nine (2.2%) arrhythmias occurred during atrial/ventricular pacing and were excluded from further analysis. Mode of PVT initiation was pause-dependent in 45 (15.6%) and 64 (60.4%) of instances in the first and second settings, respectively, for a total of 109 of 401 (27.2%). More than one type of pause-dependent and/or non-pause-dependent initiation (mean: 2.6) occurred in 94.4% of patients with ≥4 events. Coupling intervals of initiating PVCs were <350 ms, 350-500 ms, and >500 ms in 76.6%, 20.72%, and 2.7% of arrhythmia initiations, respectively., Conclusions: Pause-dependent initiation occurred in more than a quarter of arrhythmic episodes in IVF patients. PVCs having long (between 350 and 500 ms) and very long (>500 ms) coupling intervals were observed at the initiation of nearly a quarter of PVT episodes., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The objective of this study is to evaluate the influence of mixed L. acidophilus LA-5 and enrichment with microalgae (C. vulgaris and A. platensis) on metabolomic formation in a brined cheese matrix. Microbiological, compositional, and metabolomic characterization were investigated during the ripening. It was found that the nutritional quality indices of the samples were based on amino acid and fatty acid characterization. Fifty-six metabolomics including fatty acids, amino acids, organic acids, minerals, and vitamins were detected using the HPLC-DAD, GC-MS, and ICP-OES-based methods. The results indicated that the enrichment with probiotic strain and microalgae led to an increase in the nutritional quality indices such as EAAI, NI, BV, MUFA/SFA, h/H, and DFA. The chemometric analysis (e.g. HCA and PCA) presented the variance between the cheese samples based on their attributes. The identification of cheese metabolomics throughout the ripening could be used for a better understanding of the functional ingredients-cheese matrix relationships and as a directive approach for novel dairy products in other metabolomic-related studies., Competing Interests: Declaration of competing interest We declare that there are no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Hypochlorite/hypochlorous acid (ClO - /HOCl) is a biologically crucial reactive oxygen species (ROS), produced in living organisms and has a critical role as an antimicrobial agent in the natural defense system. However, when ClO - is produced excessively, it can lead to the oxidative damage of biomolecules, resulting in organ damage and various diseases. Therefore, it is imperative to have a straightforward, quick and reliable method for over watching the minimum amount of ClO - in different environments., Results: Herein, a new probe TTM, containing thienothiophene and malononitrile units, was developed for exceptionally selective and sensitive hypochlorite (ClO - ) detection. TTM demonstrated a rapid "turn-on" fluorescence response (<30 s), naked-eye detection (colorimetric), voltammetric read-out with anodic scan, low detection limit (LOD = 0.58 μM and 1.43 μM for optical and electrochemical methods, respectively) and applicability in detecting ClO - in real water samples and living cells., Significance and Novelty: This study represents one of the rare examples of a small thienothiophene-based molecule for both optical and electrochemical detections of ClO - in an aqueous medium., 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 Elsevier B.V. All rights reserved.)

Asthma is more prevalent and severe in women, especially after puberty. Studies suggest a potential link between dietary antioxidants, inflammation, and oxidative stress. This study aimed to compare the dietary intake of antioxidants in asthmatic and healthy women, evaluating their potential associations with inflammation and oxidative stress. This study analyzed 30 asthmatic and 30 healthy women's lung function, anthropometry, biochemical parameters, and dietary antioxidant intake using a 161-itemized semi-quantitative food frequency questionnaire. Additionally, the study explored connections between serum inflammatory markers and oxidative stress indicators in relation to dietary intake of antioxidant nutrients and flavonoids. Asthmatic women exhibited higher serum IL-6 levels and lower total antioxidant status compared to healthy controls. Nevertheless, no significant differences were observed in dietary antioxidant micronutrient intake. Healthy controls demonstrated a notably higher intake of anthocyanidins compared to asthmatic women. Furthermore, the study identified a negative correlation between flavonol intake and serum total oxidant status, as well as between flavan-3-ols intake and serum oxidative stress index. Dietary differences in flavonoid and flavonoid-rich foods intake among asthmatic women may affect their serum IL-6 levels and oxidative stress. Promoting a diverse diet rich in flavonoids could benefit women with asthma by mitigating inflammation and oxidative stress., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2024 JCBN.)

Hypochlorite (ClO - ), a crucial chemical in the living organism, engages in various physiological activities. However, high amounts of ClO - result in oxidative damage. In this work, a commercially available 2-aminoanthracene (AA) was used to detect ClO - . AA demonstrated distinct properties such as superior selectivity and rapid response (< 30 s) with a low detection limit (140 nM) towards ClO - in 100% buffer solution. Furthermore, the probe exhibited a notable achievement by effectively identifying the presence of ClO - in complicated water samples. In conclusion, AA offers an easy-to-use and accurate method for quantifying ClO - in complex water samples., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Sudden cardiac arrest (SCA) is a common cause of death. The majority of SCA is caused by ventricular arrhythmia due to underlying CHD. Aborted SCA with no apparent diagnosis after initial assessment with ECG, echocardiography and coronary assessment is referred to as unexplained cardiac arrest (UCA). Systematic evaluation of such patients may reveal a specific diagnosis in up to half of patients before a diagnosis of idiopathic VF is assigned. Specific diagnoses include inherited cardiac conditions, such as latent cardiomyopathies or inherited primary electrical disease. Identifying the cause of UCA is therefore not only critical for appropriate management of the SCA survivors to prevent recurrence, but also for their family members who may be at risk of the same condition. This review provides a tiered, systematic approach for the investigation of UCA., Competing Interests: Disclosure: The authors have no conflicts of interest to declare., (Copyright © The Author(s), 2023. Published by Radcliffe Group Ltd.)

Hypochlorite/hypochlorous acid (ClO - /HOCl), among the diverse reactive oxygen species, plays a vital role in various biological processes. Besides, ClO - is widely known as a sanitizer for fruits, vegetables, and fresh-cut produce, killing bacteria and pathogens. However, excessive level of ClO - can lead to the oxidation of biomolecules such as DNA, RNA, and proteins, threatening vital organs. Therefore, reliable and effective methods are of utmost importance to monitor trace amounts of ClO - . In this work, a novel BODIPY-based fluorescent probe bearing thiophene and a malononitrile moiety ( BOD-CN ) was designed and constructed to efficiently detect ClO - , which exhibited distinct features such as excellent selectivity, sensitivity (LOD = 83.3 nM), and rapid response (<30 s). Importantly, the probe successfully detected ClO - in various spiked water, milk, vegetable, and fruit samples. In all, BOD-CN offers a clearly promising approach to describe the quality of ClO - -added dairy products, water, fresh vegetables, and fruits., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Herein, the first triple-channel fluorescent probe, TTB, excited at the same wavelength (λ ex  = 360 nm) in the same sensing medium for the detection and discrimination of cyanide, hydrazine, and hypochlorite, is disclosed. While a fluorescent white color appeared (λ em  = 470 nm) with the addition of cyanide ion into the probe solution, upon addition of hydrazine and hypochlorite, green (λ em  = 503 nm) and orange (λ em  = 585 nm) fluorescent colors, respectively, were observed. A naked-eye detection for the three ions was documented. With the appearance of orange color, a mega Stokes shift of 175 nm was observed. The probe exhibited excellent selectivity and lower detection limits of 0.24 μM, 4.1 nM and 0.27 μM, and dynamic ranges of 0.0-2.0 μM, 0.0-0.05 μM and 0.0-2.0 μM for cyanide, hydrazine and hypochlorite, respectively. The sensing mechanism was investigated through computational studies before and after the addition of cyanide, hypochlorite, and hydrazine, applying density functional theory (DFT), along with the calculation of optical properties by time-dependent DFT (TD-DFT) method. The results were found to be in good agreement with the experimental values. Remarkably, the probe, TTB, successfully detected cyanide, hydrazine, and hypochlorite in complex water samples. Moreover, the detection of cyanide was successfully performed in apricot kernels, as well as hypochlorite in fruits and vegetables., 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 Elsevier B.V. All rights reserved.)

A novel fluorescent probe possessing anthracene with an indole unit was designed and synthesized to detect chromium(III) ions (Cr 3+ ) with high sensitivity and selectivity. The probe was synthesized in one step by mixing two commercially available chemicals, 2-aminoanthracene and Indole-5-carboxaldehyde. The probe molecule (ANT-In) demonstrates distinct properties, for instance, "turn-on" fluorescence response, high sensitivity and selectivity in less than one minute, and low detection limit (0.2 µM) via hydrolysis of the C = N bond. Additionally, the probe ANT-In was successfully used to identify the presence of chromium(III) ions in real water samples., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background Obesity is one of the leading risk factors for developing type 2 diabetes mellitus (T2DM). Body mass index (BMI), waist circumference, and waist/hip ratio are anthropometric measurements used to diagnose obesity. In recent years, neck circumference, one of the anthropometric indicators used in assessing obesity, has come to the fore. This study investigates the relationship between neck circumference and other anthropometric measurements and specific biochemical parameters in T2DM. Methods Four hundred sixty-four individuals with type 2 diabetes were included in the study. Subjects' body weight, height, and other anthropometric measurements like circumferences of the waist, hip, and neck were measured. BMI, waist/hip, and waist/height ratio were calculated. The biochemical tests of the subjects in the previous month from the study were accessed from the hospital information system. The relationship between anthropometric measurements and biochemical parameters with neck circumference was evaluated. Results The mean age of the subjects was 54.6±8.51 years. 56.2% were female and 43.8% were male, and the time from T2DM diagnosis was 9.9±7.49 years. Most male subjects were overweight (49.8%), and approximately one-third of the women were first-degree obese (33.0%). Body weight, BMI, waist, hip, and neck circumferences, and waist/hip and waist/height ratios were significantly higher in both male and female subjects in the neck circumference high-risk group than those in the low-risk group (p<0.05). In terms of biochemical parameters, fasting blood glucose and HbA1c values of men with neck circumference at risk were significantly higher than those in the low-risk group. Neck circumference measurements of the participants were positively correlated with body weight (r=0.543; p<0.001), height (r=0.260; p<0.001), waist circumference (r=0.562; p<0.001), hip circumference (r=0.293; p<0.001), BMI (r=0.366; p<0.001), waist/hip ratio (r=0.428, p<0.001), and waist/height ratio (r=0.393, p<0.001). Neck circumference had a low positive correlation with fasting blood glucose (r=0.165; p<0.001), HbA1c (r=0.281; p<0.001), and triglyceride (r=0.231; p<0.001) and a negative relationship with low-density lipoprotein cholesterol (r=-0.118; p=0.001). When the relationship between neck circumference and biochemical parameters was examined, it was seen that this correlation was only in men. Conclusion Neck circumference measurement is a simple and reliable method and is not affected by external factors. It correlates with other anthropometric measurements and can be used as a good indicator of the distribution of upper subcutaneous adipose tissue in T2DM. However, more studies with larger samples are needed on this subject., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Kamarli Altun et al.)

We have designed and synthesised a novel fluorescent probe with a tetraphenylethylene (TPE) scaffold as an active fluorescent unit and thiosemicarbazide (TSC) group as a recognition unit. The probe, TPE-TSC, exhibited superior selectivity towards hypochlorite (ClO - ) with a low limit of detection (2.0 nM). It also demonstrated a turn-off response for a brief period (<30 s) via an oxidation reaction. Furthermore, high-resolution mass spectrometry (HRMS) revealed that TPE-TSC reacted with ClO - by forming a carboxylic acid moiety in nearly 100% aqueous environments. More significantly, the probe detected ClO - in disinfectant, spiked milk samples, and spiked water samples. In all, TPE-TSC proposes an optimistic approach precisely for the determining the quality of milk and water contaminated with ClO - and trace amounts of ClO - in disinfectants., (Copyright © 2022 Elsevier B.V. All rights reserved.)

A novel fluorescent probe bearing triphenylamine, thiophene and thiosemicarbazide (TPA-TSC) was developed, and its distinct features were investigated. TPA-TSC demonstrated excellent selectivity towards Hg 2+ ions, with a limit of detection (0.14 nM) among the lowest reported to date. It also exhibited a turn-off response by forming stable complex for a brief period (<30 s). Job plot analysis and high-resolution mass spectrometry (HRMS) revealed that TPA-TSC bound to Hg 2+ with a 2:1 stoichiometry in an aqueous environment, remarkably the probe successfully detected Hg 2+ ions in seabass, swordfish and different samples of water. In all, TPA-TSC offers a promising method for accurately determining the quality of seafood and water samples polluted with Hg 2+ ., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The role of sleep in eating behavior has received increasing attention in recent years. This paper aimed to determine the prevalence and associations between sleep quality and mental health, anthropometric measurements, and disordered eating in university students. This cross-sectional research was conducted among 568 students (78.7% women) aged 18-25 years. Students completed a survey including demographic information, Pittsburgh Sleep Quality Index (PSQI), Eating Attitude Test-26 (EAT-26), Night Eating Questionnaire (NEQ), and Beck Depression Inventory (BDI). Anthropometric measurements were taken. Students were grouped based on poor (PSQI > 5) and good (PSQI ≤ 5) sleep quality. The students' average age was 20.32 ± 1.61 years. Additionally, 36.3% ( n  = 206) of the students had PSQI > 5, and these students had more frequent night eating syndrome (NES) and depressive symptoms. Students with PSQI > 5 had significantly higher total NEQ and BDI scores than students with PSQI ≤ 5. Significant positive correlations were found between sleep quality and its subscale scores with NEQ and BDI scores. When anthropometric measurements were evaluated according to gender, a significant difference was found between sleep quality and body mass index and waist/hip ratio in men only. There was a significant association between PSQI > 5 and NES after adjusting for age, sex, class standing, residency, smoking status, and alcohol consumption on logistic regression. Our results suggest that PSQI > 5 is a significant risk for the NES, but not other disordered eating behaviors or obesity. The relationship between sleep, depression, anthropometric measurements, and disordered eating should be further evaluated in future studies., (© The Author(s), under exclusive licence to Japanese Society of Sleep Research 2022.)

We have constructed a novel fluorescein-based fluorescent chemosensor, FL-In, functionalised with an indole moiety and capable of sensing by both the optical "turn-on" and electrochemical detection of carbonate ions (CO 3 2- ) in aqueous media. The probe exhibits excellent selectivity and a low detection limit (0.27 µM) regarding carbonate ions by a possible coordination and hydrolysis reaction mechanism. The developed probe successfully detected CO 3 2- ions in different samples of water. Also, in a simple filter paper experiment, we documented its ability to allow the monitoring of CO 3 2- with the naked eye., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: Brugada syndrome (BrS) is characterized by a unique electrocardiogram (ECG) pattern and life-threatening arrhythmias. However, the Type 1 Brugada ECG pattern is often transient, and a genetic cause is only identified in <25% of patients. We sought to identify an additional biomarker for this rare condition. As myocardial inflammation may be present in BrS, we evaluated whether myocardial autoantibodies can be detected in these patients., Methods and Results: For antibody (Ab) discovery, normal human ventricular myocardial proteins were solubilized and separated by isoelectric focusing (IEF) and molecular weight on two-dimensional (2D) gels and used to discover Abs by plating with sera from patients with BrS and control subjects. Target proteins were identified by mass spectrometry (MS). Brugada syndrome subjects were defined based on a consensus clinical scoring system. We assessed discovery and validation cohorts by 2D gels, western blots, and ELISA. We performed immunohistochemistry on myocardium from BrS subjects (vs. control). All (3/3) 2D gels exposed to sera from BrS patients demonstrated specific Abs to four proteins, confirmed by MS to be α-cardiac actin, α-skeletal actin, keratin, and connexin-43, vs. 0/8 control subjects. All (18/18) BrS subjects from our validation cohorts demonstrated the same Abs, confirmed by western blots, vs. 0/24 additional controls. ELISA optical densities for all Abs were elevated in all BrS subjects compared to controls. In myocardium obtained from BrS subjects, each protein, as well as SCN5A, demonstrated abnormal protein expression in aggregates., Conclusion: A biomarker profile of autoantibodies against four cardiac proteins, namely α-cardiac actin, α-skeletal actin, keratin, and connexin-43, can be identified from sera of BrS patients and is highly sensitive and specific, irrespective of genetic cause for BrS. The four involved proteins, along with the SCN5A-encoded Nav1.5 alpha subunit are expressed abnormally in the myocardium of patients with BrS., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: Patients' demographic and epidemiological characteristics, local variations in clinicians' knowledge and experience and types of surgery can influence peri-operative transfusion practices. Sharing data on transfusion practices and recipients may improve patients' care and implementation of Patient Blood Management (PBM)., Materials and Methods: This was a multicentre, prospective, observational, cross-sectional study that included 61 centres. Clinical and transfusion data of patients undergoing major elective surgery were collected; transfusion predictors and patients' outcomes were analysed., Results: Of 6,121 patients, 1,579 (25.8%) received a peri-operative transfusion. A total of 5,812 blood components were transfused: red blood cells (RBC), fresh-frozen plasma and platelets in 1,425 (23.3%), 762 (12.4%) and 88 (1.4%) cases, respectively). Pre-operative anaemia was identified in 2,019 (33%) patients. Half of the RBC units were used by patients in the age group 45-69 years. Specific procedures with the highest RBC use were coronary artery bypass grafting (16.9% of all units) and hip arthroplasty (14.9%). Low haemoglobin concentration was the most common indication for intra-operative RBC transfusion (57%) and plasma and platelet transfusions were mostly initiated for acute bleeding (61.3% and 61.1%, respectively). The RBC transfusion rate in study centres varied from 2% to 72%. RBC transfusion was inappropriate in 99% (n=150/151) of pre-operative, 23% (n=211/926) of intra-operative and 43% (n=308/716) of post-operative RBC transfusion episodes. Pre-operative haemoglobin, increased blood loss, open surgery and duration of surgery were the main independent predictors of intra-operative RBC transfusion. Low pre-operative haemoglobin concentration was independently associated with post-operative pulmonary complications., Conclusions: These findings identified areas for improvement in peri-operative transfusion practice and PBM implementation in Turkey.

Aims: To determine the bioequivalence of several T1 mapping sequences in myocardial characterization of diffuse myocardial fibrosis., Methods and Results: We performed an intra-individual sequence comparison of three types of T1 mapping sequences [MOdified Look-Locker Inversion recovery (MOLLI), Shortened MOdified Look-Locker Inversion recovery ((sh)MOLLI), and SAturation recovery single-SHot Acquisition (SASHA)]. We employed two model diseases of diffuse interstitial fibrosis [patients with non-ischaemic dilated cardiomyopathy (NIDCM), n = 32] and aortic stenosis [(AS), n = 25)]. Twenty-six healthy individuals served as controls. Relationship with collagen volume fraction (CVF) was assessed using endomyocardial biopsies (EMB) intraoperatively in 12 AS patients. T2 mapping (GraSE) was also performed. Myocardial native T1 with MOLLI and shMOLLI showed, firstly, an excellent discriminatory accuracy between health and disease [area under the curves (P-value): 0.94 (0.88-0.99); 0.87 (0.79-0.94); 0.61 (0.49-0.72)], secondly, relationship between histological CVF [native T1 MOLLI vs. shMOLLI vs. SASHA: r = 0.582 (P = 0.027), r = 0.524 (P = 0.046), r = 0.443 (P = 0.150)], and thirdly, with native T2 [r = 0.628(P < 0.001), r = 0.459 (P = 0.003), r = 0.211 (P = 0.083)]. The respective relationships for extracellular volume fraction with CVF [r = 0.489 (P = 0.044), r = 0.417 (0.071), r = 0.353 (P = 0.287)] were significant for MOLLI, but not other sequences. In AS patients, native T2 was significantly higher compared to controls, and associated with levels of C-reactive protein and troponin., Conclusion: T1 mapping sequences differ in their bioequivalence for discrimination between health and disease as well as associations with diffuse myocardial fibrosis.

Background: Extracellular matrix (ECM) remodeling contributes to in-stent restenosis and thrombosis. Despite its important clinical implications, little is known about ECM changes post-stent implantation., Methods: Bare-metal and drug-eluting stents were implanted in pig coronary arteries with an overstretch under optical coherence tomography guidance. Stented segments were harvested 1, 3, 7, 14, and 28 days post-stenting for proteomics analysis of the media and neointima., Results: A total of 151 ECM and ECM-associated proteins were identified by mass spectrometry. After stent implantation, proteins involved in regulating calcification were upregulated in the neointima of drug-eluting stents. The earliest changes in the media were proteins involved in inflammation and thrombosis, followed by changes in regulatory ECM proteins. By day 28, basement membrane proteins were reduced in drug-eluting stents in comparison with bare-metal stents. In contrast, the large aggregating proteoglycan aggrecan was increased. Aggrecanases of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family contribute to the catabolism of vascular proteoglycans. An increase in ADAMTS-specific aggrecan fragments was accompanied by a notable shift from ADAMTS1 and ADAMTS5 to ADAMTS4 gene expression after stent implantation. Immunostaining in human stented coronary arteries confirmed the presence of aggrecan and aggrecan fragments, in particular, at the contacts of the stent struts with the artery. Further investigation of aggrecan presence in the human vasculature revealed that aggrecan and aggrecan cleavage were more abundant in human arteries than in human veins. In addition, aggrecan synthesis was induced on grafting a vein into the arterial circulation, suggesting an important role for aggrecan in vascular plasticity. Finally, lack of ADAMTS-5 activity in mice resulted in an accumulation of aggrecan and a dilation of the thoracic aorta, confirming that aggrecanase activity regulates aggrecan abundance in the arterial wall and contributes to vascular remodeling., Conclusions: Significant differences were identified by proteomics in the ECM of coronary arteries after bare-metal and drug-eluting stent implantation, most notably an upregulation of aggrecan, a major ECM component of cartilaginous tissues that confers resistance to compression. The accumulation of aggrecan coincided with a shift in ADAMTS gene expression. This study provides the first evidence implicating aggrecan and aggrecanases in the vascular injury response after stenting., (© 2017 The Authors.)

Background: The identification of patients with high-risk atherosclerotic plaques prior to the manifestation of clinical events remains challenging. Recent findings question histology- and imaging-based definitions of the "vulnerable plaque," necessitating an improved approach for predicting onset of symptoms., Methods: We performed a proteomics comparison of the vascular extracellular matrix and associated molecules in human carotid endarterectomy specimens from 6 symptomatic versus 6 asymptomatic patients to identify a protein signature for high-risk atherosclerotic plaques. Proteomics data were integrated with gene expression profiling of 121 carotid endarterectomies and an analysis of protein secretion by lipid-loaded human vascular smooth muscle cells. Finally, epidemiological validation of candidate biomarkers was performed in two community-based studies., Results: Proteomics and at least one of the other two approaches identified a molecular signature of plaques from symptomatic patients that comprised matrix metalloproteinase 9, chitinase 3-like-1, S100 calcium binding protein A8 (S100A8), S100A9, cathepsin B, fibronectin, and galectin-3-binding protein. Biomarker candidates measured in 685 subjects in the Bruneck study were associated with progression to advanced atherosclerosis and incidence of cardiovascular disease over a 10-year follow-up period. A 4-biomarker signature (matrix metalloproteinase 9, S100A8/S100A9, cathepsin D, and galectin-3-binding protein) improved risk prediction and was successfully replicated in an independent cohort, the SAPHIR study., Conclusion: The identified 4-biomarker signature may improve risk prediction and diagnostics for the management of cardiovascular disease. Further, our study highlights the strength of tissue-based proteomics for biomarker discovery., Funding: UK: British Heart Foundation (BHF); King's BHF Center; and the National Institute for Health Research Biomedical Research Center based at Guy's and St Thomas' NHS Foundation Trust and King's College London in partnership with King's College Hospital. Austria: Federal Ministry for Transport, Innovation and Technology (BMVIT); Federal Ministry of Science, Research and Economy (BMWFW); Wirtschaftsagentur Wien; and Standortagentur Tirol.

Objectives: The study sought to examine prognostic relevance of T1 mapping parameters (based on a T1 mapping method) in nonischemic dilated cardiomyopathy (NIDCM) and compare them with conventional markers of adverse outcome., Background: NIDCM is a recognized cause of poor clinical outcome. NIDCM is characterized by intrinsic myocardial remodeling due to complex pathophysiological processes affecting myocardium diffusely. Lack of accurate and noninvasive characterization of diffuse myocardial disease limits recognition of early cardiomyopathy and effective clinical management in NIDCM. Cardiac magnetic resonance (CMR) supports detection of diffuse myocardial disease by T1 mapping., Methods: This is a prospective observational multicenter longitudinal study in 637 consecutive patients with dilated NIDCM (mean age 50 years [interquartile range: 37 to 76 years]; 395 males [62%]) undergoing CMR with T1 mapping and late gadolinium enhancement (LGE) at 1.5-T and 3.0-T. The primary endpoint was all-cause mortality. A composite of heart failure (HF) mortality and hospitalization was a secondary endpoint., Results: During a median follow-up period of 22 months (interquartile range: 19 to 25 months), we observed a total of 28 deaths (22 cardiac) and 68 composite HF events. T1 mapping indices (native T1 and extracellular volume fraction), as well as the presence and extent of LGE, were predictive of all-cause mortality and HF endpoint (p < 0.001 for all). In multivariable analyses, native T1 was the sole independent predictor of all-cause and HF composite endpoints (hazard ratio: 1.1; 95% confidence interval: 1.06 to 1.15; hazard ratio: 1.1; 95% confidence interval: 1.05 to 1.1; p < 0.001 for both), followed by the models including the extent of LGE and right ventricular ejection fraction, respectively., Conclusions: Noninvasive measures of diffuse myocardial disease by T1 mapping are significantly predictive of all-cause mortality and HF events in NIDCM. We provide a basis for a novel algorithm of risk stratification in NIDCM using a complementary assessment of diffuse and regional disease by T1 mapping and LGE, respectively., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

In an endotoxaemic mouse model of sepsis, a tissue-based proteomics approach for biomarker discovery identified long pentraxin 3 (PTX3) as the lead candidate for inflamed myocardium. When the redox-sensitive oligomerization state of PTX3 was further investigated, PTX3 accumulated as an octamer as a result of disulfide-bond formation in heart, kidney, and lung-common organ dysfunctions seen in patients with sepsis. Oligomeric moieties of PTX3 were also detectable in circulation. The oligomerization state of PTX3 was quantified over the first 11 days in critically ill adult patients with sepsis. On admission day, there was no difference in the oligomerization state of PTX3 between survivors and non-survivors. From day 2 onward, the conversion of octameric to monomeric PTX3 was consistently associated with a greater survival after 28 days of follow-up. For example, by day 2 post-admission, octameric PTX3 was barely detectable in survivors, but it still constituted more than half of the total PTX3 in non-survivors (p < 0.001). Monomeric PTX3 was inversely associated with cardiac damage markers NT-proBNP and high-sensitivity troponin I and T. Relative to the conventional measurements of total PTX3 or NT-proBNP, the oligomerization of PTX3 was a superior predictor of disease outcome., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)