Thiadiazole-, selenadiazole- and triazole-fused anthraquinones as G-quadruplex targeting anticancer compounds.

G-quadruplex (G4) ligands attract considerable attention as potential anticancer therapeutics. In this study we proposed an original scheme for synthesis of azole-fused anthraquinones and prepared a series of G4 ligands carrying amino- or guanidinoalkylamino side chains. The heterocyclic core and structure of the terminal groups strongly affect on binding to G4-forming oligonucleotides, cellular accumulation and antitumor potency of compounds. In particular, thiadiazole- and selenadiazole- but not triazole-based ligands inhibit the proliferation of tumor cells (e.g. K562 leukemia) and stabilize primarily telomeric and c-MYC G4s. Anthraselenadiazole derivative 11a showed a good affinity to c-MYC G4 in vitro and down-regulated expression of c-MYC oncogene in cellular conditions. Further studies revealed that anthraselenadiazole 11a provoked cell cycle arrest and apoptosis in a dose- and time-dependent manner inhibiting K562 cells growth. Taken together, this work gives a valuable example that the closely related heterocycles may cause a significant difference in biological properties of G4 ligands.

High Ferritin and Low Total Iron-Binding Capacity in Plasma Predict All-Cause Mortality During the First 3 Years of Hemodialysis in Patients with End-Stage Chronic Kidney Disease.

Aim: To determine all-cause mortality rate and the predictive value of plasma ferritin and total iron-binding capacity (TIBC) concentrations for mortality during the first 3 years of hemodialysis in patients with end-stage chronic renal disease (ESRD). Methods: We conducted a study on 174 ESRD patients (estimated Glomerular Filtration Rate < 15 mL/min/1.73m2). The plasma TIBC level was quantified by the ELISA method in all patients at the time before hemodialysis. Based on TIBC concentration, patients were divided equally into 2 groups. Each group had 87 patients. Patients were initiated on hemodialysis, and patients who died from any cause during the first 3 years of hemodialysis were recorded. Results: The all-cause mortality rate of ESRD patients in the first 3 years of maintenance hemodialysis was 22.9%. Plasma high hs-CRP, high ferritin, and low TIBC concentrations were independent factors associated with all-cause mortality in the patients. Plasma ferritin (cut-off value = 454.2 ng/L) and TIBC (cut-off value = 39.84 µmol/L) were predictors of all-cause mortality, AUC is: 0.772; 0.723, p < 0.001. Conclusion: Plasma ferritin and TIBC were good predictors of all-cause mortality in ESRD patients during the first 3 years of hemodialysis.

Diagnosis of sudden cardiac arrest using principal component analysis in automated external defibrillators.

Sudden cardiac arrest (SCA) consisting of ventricular fibrillation and ventricular tachycardia considered as shockable rhythms is a life-threatening heart disease, which is treated efficiently by the automated external defibrillator (AED). This work proposes a novel design of the SAA, which includes a k-nearest neighbors model and a subset of 8 features extracted from the ECG segments, for the SCA diagnosis on the electrocardiogram (ECG) signal. These features are addressed as the most productive subset among 31 input features based on the evaluation of the feature correlation. The recursive feature elimination algorithm combined with the Boosting model and wise-patient fivefold cross-validation method is adopted for the calculation of the average feature importance, which shows the degree of feature correlation, to construct various input feature subsets. Moreover, component feature combinations known as the representatives of the input feature subsets with an enormous level of correlation and independence are transformed from the input subsets by the principal component analysis method. The wise-patient fivefold cross-validation procedure is used for the evaluation of these component feature combinations on the validation set. The proposed SAA is certainly efficient for SCA detection with a small number of the extracted feature and relatively high diagnosis performance such as accuracy of 99.52%, sensitivity of 97.69%, and specificity of 99.91%.

Perfluorocarbon Nanoemulsions with Fluorous Chlorin-Type Photosensitizers for Antitumor Photodynamic Therapy in Hypoxia.

The efficacy of photodynamic therapy (PDT) strictly depends on the availability of molecular oxygen to trigger the light-induced generation of reactive species. Fluorocarbons have an increased ability to dissolve oxygen and are attractive tools for gas delivery. We synthesized three fluorous derivatives of chlorin with peripheral polyfluoroalkyl substituents. These compounds were used as precursors for preparing nanoemulsions with perfluorodecalin as an oxygen depot. Therefore, our formulations contained hydrophobic photosensitizers capable of absorbing monochromatic light in the long wavelength region and the oxygen carrier. These modifications did not alter the photosensitizing characteristics of chlorin such as the generation of singlet oxygen, the major cytocidal species in PDT. Emulsions readily entered HCT116 colon carcinoma cells and accumulated largely in mitochondria. Illumination of cells loaded with emulsions rapidly caused peroxidation of lipids and the loss of the plasma membrane integrity (photonecrosis). Most importantly, in PDT settings, emulsions potently sensitized cells cultured under prolonged (8 weeks) hypoxia as well as cells after oxygen depletion with sodium sulfite (acute hypoxia). The photodamaging potency of emulsions in hypoxia was significantly more pronounced compared to emulsion-free counterparts. Considering a negligible dark cytotoxicity, our materials emerge as efficient and biocompatible instruments for PDT-assisted eradication of hypoxic cells.

Learning meaningful latent space representations for patient risk stratification: Model development and validation for dengue and other acute febrile illness.

Background: Increased data availability has prompted the creation of clinical decision support systems. These systems utilise clinical information to enhance health care provision, both to predict the likelihood of specific clinical outcomes or evaluate the risk of further complications. However, their adoption remains low due to concerns regarding the quality of recommendations, and a lack of clarity on how results are best obtained and presented. Methods: We used autoencoders capable of reducing the dimensionality of complex datasets in order to produce a 2D representation denoted as latent space to support understanding of complex clinical data. In this output, meaningful representations of individual patient profiles are spatially mapped in an unsupervised manner according to their input clinical parameters. This technique was then applied to a large real-world clinical dataset of over 12,000 patients with an illness compatible with dengue infection in Ho Chi Minh City, Vietnam between 1999 and 2021. Dengue is a systemic viral disease which exerts significant health and economic burden worldwide, and up to 5% of hospitalised patients develop life-threatening complications. Results: The latent space produced by the selected autoencoder aligns with established clinical characteristics exhibited by patients with dengue infection, as well as features of disease progression. Similar clinical phenotypes are represented close to each other in the latent space and clustered according to outcomes broadly described by the World Health Organisation dengue guidelines. Balancing distance metrics and density metrics produced results covering most of the latent space, and improved visualisation whilst preserving utility, with similar patients grouped closer together. In this case, this balance is achieved by using the sigmoid activation function and one hidden layer with three neurons, in addition to the latent dimension layer, which produces the output (Pearson, 0.840; Spearman, 0.830; Procrustes, 0.301; GMM 0.321). Conclusion: This study demonstrates that when adequately configured, autoencoders can produce two-dimensional representations of a complex dataset that conserve the distance relationship between points. The output visualisation groups patients with clinically relevant features closely together and inherently supports user interpretability. Work is underway to incorporate these findings into an electronic clinical decision support system to guide individual patient management.

Performance of the 2019 ESC/EASD guideline strategy for the screening of silent coronary artery disease in patients with diabetes.

BACKGROUND: The 2019 guidelines for cardiovascular risk stratification by the European Society of Cardiology and European Association for the Study of Diabetes (ESC-EASD) suggested screening for silent coronary disease in very high risk patients with severe target organ damage (TOD) (i.e. peripheral occlusive arterial disease or severe nephropathy) or high coronary artery calcium (CAC) score. This study aimed to test the validity of this strategy. METHODS: In this retrospective study, we included 385 asymptomatic patients with diabetes and no history of coronary disease but with TOD or ≥ 3 risk factors in addition to diabetes. CAC score was measured using computed tomography scan and a stress myocardial scintigraphy was performed to detect silent myocardial ischemia (SMI), with subsequent coronary angiography in those with SMI. Various strategies to select patients to be screened for SMI were tested. RESULTS: CAC score was ≥ 100 Agatston units (AU) in 175 patients (45.5%). SMI was present in 39 patients (10.1%) and among the 30 patients who underwent angiography, 15 had coronary stenoses and 12 had a revascularization procedure. The most effective strategy consisted in performing myocardial scintigraphy in the 146 patients with severe TOD and, among the 239 other patients without severe TOD, in those with CAC ≥ 100 AU: this strategy provided 82% sensitivity for SMI diagnosis, and identified all the patients with stenoses. CONCLUSION: The ESC-EASD guidelines suggesting SMI screening in asymptomatic patients with very high risk assessed by severe TOD or high CAC score appears effective and could identify all the patients with stenoses eligible for revascularization.

Clinical relevance of coronary risk classification and reclassification with coronary artery calcium score in asymptomatic people living with diabetes. An observational study.

AIMS: To explore (i) in what proportion and direction coronary artery calcium (CAC) score reclassifies coronary risk in asymptomatic diabetic patients at high a priori coronary risk, and (ii) whether screening for asymptomatic myocardial ischemia / coronary stenosis only in patients at very high coronary risk - whether a priori or combined with those reclassified at very high risk according to their CAC score - has good sensitivity to detect these conditions. METHODS: We retrospectively selected 377 asymptomatic primary prevention diabetic patients at high or very high a priori coronary risk according to national guidelines. All had their CAC score measured and underwent stress myocardial scintigraphy to detect myocardial ischemia. Those identified with ischemia then had a coronary angiography to identify coronary stenoses. RESULTS: Of the selected patients, 242 and 135 patients had a high and very high a priori coronary risk, respectively. After taking into account their CAC score, the former were reclassified into three risk categories: moderate (n = 159, 66%), high (n = 38) and very high (45 patients) risk. Myocardial ischemia was identified in 35 patients and coronary stenoses in 14 of the latter. Had a stress scintigraphy been performed only in the 135 patients at very high risk a priori, 18 patients would have been detected with ischemia (sensitivity 51%), and 9 with coronary stenoses (sensitivity 64%). Had a scintigraphy also been performed on the 45 patients at very high risk after CAC-reclassification, an additional 7 and 5 patients with ischemia and coronary stenoses, respectively, would have been identified. CONCLUSION: Following national guidelines, 66% of our population of asymptomatic diabetic persons at high a priori coronary risk were reclassified into the moderate risk category, translating into less stringent goals for risk factor control. Eighteen percent were reclassified into the very high-risk category, leading to 100% detection sensitivity for patients with ischemia and coronary stenoses.

Detection of virulence, specific genes and antibiotic resistance of isolated Salmonella spp. strains from rabbits infected with salmonellosis

Salmonella spp. are pathogens involved in most salmonellosis in rabbits. This study examined Salmonella disease in rabbits raised in Thua Thien Hue, Vietnam. Two hundred and 56 rectal swabs of rabbits were taken, and a carrier rate of 33.98% was found. In addition, all the isolated Salmonella spp. strains were 100% motile; positive for H2S, catalase, Voges Proskauer, coagulase, citrate, maltose, and dextrose; and negative for indole, methyl red, urease, oxidase, sucrose, and lactose. The Kirby-Bauer method showed that these Salmonella strains were susceptible to doxycycline (93.2%), tetracycline (84.1%), and levofloxacin (65.9%). On the other hand, they were highly resistant to streptomycin (95.5%), ampicillin (93.2%), colistin (40.9%), and gentamicin (34.1%). Furthermore, polymerase chain reaction used to screen for virulence and specific genes of Salmonella strains showed that all Salmonella strains isolated carried InvA, fimA, and Stn.

Oligohexamethylene Guanidine Derivative as a Means to Prevent Biological Fouling of a Polymer-Based Composite Optical Oxygen Sensor.

The use of biocidal agents is a common practice for protection against biofouling in biomass-rich environments. In this paper, oligohexamethyleneguanidine (OHMG) polymer, known for its biocidal properties, was further modified with para-aminosalicylic acid (PAS) to enhance its properties against microorganisms coated with a lipid membrane. The structure of the product was confirmed by 1H NMR, 13C NMR, and FTIR spectroscopy. The values of the minimum inhibitory concentration (MIC) against Mycobacterium smegmatis ATCC 607 and Pseudomonas chlororaphis 449 were found to be 1.40 and 1.05 µg/mL, respectively. The synthesized substance was used as an additive to the polymer matrix of the composite optical oxygen sensor material. A series of samples with different contents of OHMG-PAS was prepared using a co-dissolution method implying the fabrication of a coating from a solution containing both polymers. It turned out that the mutual influence of the components significantly affects the distribution of the indicator in the matrix, surface morphology, and contact angle. The optimal polymer content turned out to be wt.3%, at which point the water contact angle reaches almost 122°, and the fouling rate decreases by almost five times, which is confirmed by both the respiratory MTT assay and confocal microscopy with staining. This opens up prospects for creating stable and biofouling-resistant sensor elements for use in air tanks or seawater.

Analysis of ESAFORM 2021 cup drawing benchmark of an Al alloy, critical factors for accuracy and efficiency of FE simulations.

This article details the ESAFORM Benchmark 2021. The deep drawing cup of a 1 mm thick, AA 6016-T4 sheet with a strong cube texture was simulated by 11 teams relying on phenomenological or crystal plasticity approaches, using commercial or self-developed Finite Element (FE) codes, with solid, continuum or classical shell elements and different contact models. The material characterization (tensile tests, biaxial tensile tests, monotonic and reverse shear tests, EBSD measurements) and the cup forming steps were performed with care (redundancy of measurements). The Benchmark organizers identified some constitutive laws but each team could perform its own identification. The methodology to reach material data is systematically described as well as the final data set. The ability of the constitutive law and of the FE model to predict Lankford and yield stress in different directions is verified. Then, the simulation results such as the earing (number and average height and amplitude), the punch force evolution and thickness in the cup wall are evaluated and analysed. The CPU time, the manpower for each step as well as the required tests versus the final prediction accuracy of more than 20 FE simulations are commented. The article aims to guide students and engineers in their choice of a constitutive law (yield locus, hardening law or plasticity approach) and data set used in the identification, without neglecting the other FE features, such as software, explicit or implicit strategy, element type and contact model.

A review of progress and an advanced method for shock advice algorithms in automated external defibrillators.

Shock advice algorithm plays a vital role in the detection of sudden cardiac arrests on electrocardiogram signals and hence, brings about survival improvement by delivering prompt defibrillation. The last decade has witnessed a surge of research efforts in racing for efficient shock advice algorithms, in this context. On one hand, it has been reported that the classification performance of traditional threshold-based methods has not complied with the American Heart Association recommendations. On the other hand, the rise of machine learning and deep learning-based counterparts is paving the new ways for the development of intelligent shock advice algorithms. In this paper, we firstly provide a comprehensive survey on the development of shock advice algorithms for rhythm analysis in automated external defibrillators. Shock advice algorithms are categorized into three groups based on the classification methods in which the detection performance is significantly improved by the use of machine learning and/or deep learning techniques instead of threshold-based approaches. Indeed, in threshold-based shock advice algorithms, a parameter is calculated as a threshold to distinguish shockable rhythms from non-shockable ones. In contrast, machine learning-based methods combine multiple parameters of conventional threshold-based approaches as a set of features to recognize sudden cardiac arrest. Noticeably, those features are possibly extracted from stand-alone ECGs, alternative signals using various decomposition techniques, or fully augmented ECG segments. Moreover, these signals can be also used directly as the input channels of deep learning-based shock advice algorithm designs. Then, we propose an advanced shock advice algorithm using a support vector machine classifier and a feature set extracted from a fully augmented ECG segment with its shockable and non-shockable signals. The relatively high detection performance of the proposed shock advice algorithm implies a potential application for the automated external defibrillator in the practical clinic environment. Finally, we outline several interesting yet challenging research problems for further investigation.

Low serum prealbumin concentration predicts long-term mortality in maintenance hemodialysis patients with hepatitis B and/or C virus infections.

BACKGROUND AND AIM: A low serum prealbumin concentration is common in maintenance hemodialysis patients with hepatitis B and C and may be associated with mortality. In this study, we assessed Department of Nephrology and Hemodialysis predictive value of a low serum prealbumin concentration on mortality in HD patients using reused low-flux dialyzers who were infected with hepatitis B and/or C virus. METHODS: We used serum prealbumin levels to predict the long-term mortality of 326 hemodialysis patients. The patients were divided into two groups: group 1 (n = 140, with hepatitis B and/or C virus infections), and group 2 (n = 186, without hepatitis virus infections). RESULTS: During a 5-year follow-up, there were 75 deaths due to all-cause mortality (23.0%). Mortality was significantly higher (P < 0.001) in patients with hepatitis B and/or C infection (44%) than in those without hepatitis infection (8%). Serum prealbumin was lower in the hepatitis infected group and mortality group than in non-infected group and survival group. Multivariate Cox regression analysis showed that long duration of HD and lower serum prealbumin and albumin were related to mortality in patients undergoing maintenance HD. Receiver operating characteristic curves showed that serum prealbumin had a good prognostic value in predicting mortality in both groups with hepatitis B and/or C virus infection and without hepatitis infection (AUC = 0.792 [95% confidence interval: 0.714-0.87], P < 0.001; cut-off value = 24.5 mg/dl, sensitivity = 62.3%, and specificity = 88.6%). CONCLUSION: In HD patients, serum prealbumin was a good prognostic biomarker of mortality in both groups of patients with hepatitis B and/or C virus infections and without hepatitis infections.

Epicardial adipose tissue volume and myocardial ischemia in asymptomatic people living with diabetes: a cross-sectional study.

BACKGROUND: Epicardial adipose tissue (EAT) is considered a novel diagnostic marker for cardiometabolic disease. This study aimed to evaluate whether EAT volume was associated with stress-induced myocardial ischemia in asymptomatic people living with diabetes-independently of confounding factors-and whether it could predict this condition. METHODS: We included asymptomatic patients with diabetes and no coronary history, who had undergone both a stress a myocardial scintigraphy to diagnose myocardial ischemia, and a computed tomography to measure their coronary artery calcium (CAC) score. EAT volume was retrospectively measured from computed tomography imaging. Determinants of EAT volume and asymptomatic myocardial ischemia were evaluated. RESULTS: The study population comprised 274 individuals, including 153 men. Mean (± standard deviation) age was 62 ± 9 years, and 243, 23 and 8 had type 2, type 1, or another type of diabetes, respectively. Mean body mass index was 30 ± 6 kg/m2, and mean EAT volume 96 ± 36 cm3. Myocardial ischemia was detected in 32 patients (11.7%). EAT volume was positively correlated with age, body mass index and triglyceridemia, but negatively correlated with HbA1c, HDL- and LDL-cholesterol levels. Furthermore, EAT volume was lower in people with retinopathy, but higher in men, in current smokers, in patients with nephropathy, those with a CAC score > 100 Agatston units, and finally in individuals with myocardial ischemia (110 ± 37 cm3 vs 94 ± 37 cm3 in those without myocardial ischemia, p < 0.05). The association between EAT volume and myocardial ischemia remained significant after adjustment for gender, diabetes duration, peripheral macrovascular disease and CAC score. We also found that area under the ROC curve analysis showed that EAT volume (AROC: 0.771 [95% confidence interval 0.683-0.858]) did not provide improved discrimination of myocardial ischemia over the following classic factors: gender, diabetes duration, peripheral macrovascular disease, retinopathy, nephropathy, smoking, atherogenic dyslipidemia, and CAC score (AROC 0.773 [0.683-0.862]). CONCLUSIONS: EAT may play a role in coronary atherosclerosis and coronary circulation in patients with diabetes. However, considering EAT volume is not a better marker for discriminating the risk of asymptomatic myocardial ischemia than classic clinical data.

High Serum Uric Acid and High-Sensitivity C Reactive Protein Concentrations Predict Three-Year Cardiovascular Mortality in Patients Treated With Continuous Ambulatory Peritoneal Dialysis.

AIMS: This study aims to access the predicting value of serum uric acid (UA) and high-sensitivity C reactive protein (hs-CRP) concentration on three-year cardiovascular-related mortality in patients performing continuous ambulatory peritoneal dialysis (CAPD). METHODS: A total of267 CAPD patients [150 male (56.2%); mean age 48.93 ± 13.58 years] were included in our study. All patients had measured serum UA and hs-CRP concentration. A high-sensitivity particle-enhanced immunoturbidimetric assay determined serum hs-CRP; serum UA levels were determined using an enzymatic colorimetric assay. All patients were followed for three years to detect cardiovascular-related mortality by cardiologists and stroke specialists. RESULTS: Mean serum UA level was 415.16 ± 84.28 µmol/L, 58.4% of patients had increased serum UA level. Median serum hs-CRP level was 2 (1-4) mg/L, 12.4% of patients had increased serum hs-CRP level. During 36 months of follow-up, 41 patients (15.4%) had cardiovascular-related mortality. The results of Cox proportional hazards regression showed that hypertension, diabetes, high serum UA and hs-CRP were risk factors that related to cardiovascular-related mortality (p<0.05). The receiver operating characteristic (ROC) curve and Kaplan-Meier analysis results showed that UA and hs-CRP level had predictive value for three-year cardiovascular-related mortality in CAPD patients [uric acid: area under the curve (AUC)=0.822; hs-CRP: AUC=0.834, p < 0.001]. CONCLUSION: High serum UA and hs-CRP levels were predictive factors of cardiovascular-related mortality in CAPD patients.

Association of serum adiponectin and leptin levels with renal function in kidney transplant recipients with or without new-onset diabetes after transplantation.

PURPOSE: To evaluate serum adiponectin and leptin concentration in new-onset diabetes after transplantation (NODAT) and non-NODAT patients and association with renal function in kidney transplant recipients (KTRs). PATIENTS AND METHODS: A study of 314 consecutive adults KTRs divided into four groups: 236 individuals without NODAT who had renal insufficiency (RI; n = 56) or normal renal function (n = 180) and 78 patients with NODAT who had RI (n = 17) or normal renal function (n = 61). NODAT was diagnosed based on venous fasting blood glucose or HbA1c with the criteria of the American Diabetes Association. Renal insufficiency was defined according to KDOQI 2002 guidelines. RESULTS: In the NODAT group, the median level of serum adiponectin was lower than that of non-NODAT one (30 µg/ml vs 37.15 µg/ml, p < 0.001); in contrast, the median leptin concentration was higher (4.27 ng/ml vs 4.05 ng/ml, p = 0.024). In the RI group, both median serum adiponectin and leptin levels were higher than those of non-RI one (Adiponectin: 40.01 µg/ml vs 33.7 µg/ml; Leptin: 4.51 ng/ml vs 3.91 ng/ml, p < 0.001 both). We found that BMI was related to both adiponectin and leptin levels in both NODAT, non-NODAT, and all subject groups, based on univariate and multivariate linear regression analysis. CONCLUSION: New-onset diabetes after transplantation, BMI, and renal insufficiency were affected to the serum level of adiponectin and leptin in KTRs.

Serum osteoprotegerin level in hemodialysis patients using low-flux reused dialyzer in relation to atherosclerosis.

AIMS: To assess the relation of high serum OPG level and carotid atherosclerosis in maintenance hemodialysis (MHD) patients using low-flux reused dialyzer. MATERIALS AND METHODS: We examined 209 MHD patients with and without carotid atherosclerosis (83 patients and 126 patients) to establish the relation between OPG and atherosclerosis. RESULTS: The proportion of carotid atherosclerosis was 39.7%. The median serum OPG level was 45.3 pmol/L. Serum OPG had a good predicting value for atherosclerosis in MHD patients using low-flux reused dialyzer (AUC = 0.934, p < 0.001, cutoff value = 43.35 pmol/L, Se = 81.3%, Sp = 90.9%). CONCLUSIONS: In this study, serum OPG had a good predicting value for atherosclerosis in MHD patients using low-flux reused dialyzer.

Epicardial adipose tissue volume and coronary calcification among people living with diabetes: a cross-sectional study.

BACKGROUND: Epicardial adipose tissue (EAT) has anatomic and functional proximity to the heart and is considered a novel diagnostic marker and therapeutic target in cardiometabolic diseases. The aim of this study was to evaluate whether EAT volume was associated with coronary artery calcification (CAC) in people living with diabetes, independently of confounding factors. METHODS: We included all consecutive patients with diabetes whose EAT volume and CAC score were measured using computed tomography between January 1, 2019 and September 30, 2020 in the Department of Diabetology-Endocrinology-Nutrition at Avicenne Hospital, France. Determinants of EAT volume and a CAC score ≥ 100 Agatston units (AU) were evaluated. RESULTS: The study population comprised 409 patients (218 men). Mean (± standard deviation) age was 57 ± 12 years, and 318, 56 and 35 had type 2 (T2D), type 1 (T1D), or another type of diabetes, respectively. Mean body mass index (BMI) was 29 ± 6 kg/m2, mean AET volume 93 ± 38 cm3. EAT volume was positively correlated with age, BMI, pack-year smoking history and triglyceridaemia, but negatively correlated with HDL-cholesterol level. Furthermore, it was lower in people with retinopathy, but higher in men, in Caucasian people, in patients on antihypertensive and lipid-lowering medication, in people with nephropathy, and finally in individuals with a CAC ≥ 100 AU (CAC < 100 vs CAC ≥ 100: 89 ± 35 vs 109 ± 41 cm3, respectively, p < 0.05). In addition to EAT volume, other determinants of CAC ≥ 100 AU (n = 89, 22%) were age, T2D, ethnicity, antihypertensive and lipid-lowering medication, cumulative tobacco consumption, retinopathy, macular edema and macrovascular disease. Multivariable analysis considering all these determinants as well as gender and BMI showed that EAT volume was independently associated with CAC ≥ 100 AU (per 10 cm3 increase: OR 1.11 [1.02-1.20]). CONCLUSIONS: EAT volume was independently associated with CAC. As it may play a role in coronary atherosclerosis in patients with diabetes, reducing EAT volume through physical exercise, improved diet and pharmaceutical interventions may improve future cardiovascular risk outcomes in this population.

Ethacrynic acid, a loop diuretic, suppresses epithelial-mesenchymal transition of A549 lung cancer cells via blocking of NDP-induced WNT signaling.

Lung cancer is one of the leading causes of death in cancer patients. Epithelial-mesenchymal transition (EMT) plays an important role in lung cancer progression. Therefore, for lung cancer treatment, it is crucial to find substances that inhibit EMT. Ethacrynic acid (ECA) is a diuretic that inhibits cellular ion flux and exerts anticancer effects. However, the effects of ECA on EMT in lung cancer remain unclear. We examined the effects of ECA on sphingosylphosphorylcholine (SPC) or TGF-ß1-induced EMT process in A549 and H1299 cells via reverse transcription polymerase chain reaction and Western blotting. We found that ECA inhibited SPC-induced EMT and SPC-induced WNT signalling in EMT. We observed that SPC induces the expression of NDP [Norrie disease protein] and WNT-2, whereas ECA suppressed their expression. SPC-induced WNT activation, EMT, migration, and invasion were suppressed by NDP small-interfering RNA (siNDP), but NDP overexpression (pNDP) enhanced these events in A549 and H1299 cells. Accordingly, NDP expression may influence lung cancer prognosis. In summary, our results revealed that ECA inhibited SPC or TGF-ß1-induced EMT in A549 and H1299 lung cancer cells by downregulating NDP expression and inhibiting WNT activation. Therefore, ECA might be a new drug candidate for lung cancer treatment.

Clinical, Virological, and Cytokine Profiles of Children Infected with Dengue Virus during the Outbreak in Southern Vietnam in 2017.

Dengue virus (DENV) infection is a major cause of morbidity and mortality in Vietnam, and the incidence is higher and more consistent in the southern part of the country. This study investigated the circulation of DENV serotypes, viremia levels, immunological status, and cytokine levels, with disease severities among children infected in 2017 in Ho Chi Minh City, Southern Vietnam. Acute and convalescent serum samples were collected from clinically diagnosed dengue children. They were confirmed to have DENV infection by NS1 antigen, IgM and IgG ELISAs, virus isolation, and conventional and real-time RT-PCR. Measurement of 10 cytokine levels was performed in the serum samples. All the children were dengue IgM positive; 28% and 72% of them had primary and secondary DENV infections, respectively, whereas 54% of those with secondary infection were children with dengue with warning signs and with severe dengue. Any or mixed infection of the four serotypes of DENV RNA was detected in 58 children. Twenty DENV strains (DENV-1 = 16 and DENV-4 = 4) were isolated. Levels of IFN-γ, TNF-α, MCP-1, IL-10, and IL-6 were significantly higher in severe dengue cases. We report the predominance of DENV-1 over other serotypes in the 2017 dengue outbreak in Southern Vietnam. Our data showed that cytokine expressions were correlated with dengue pathogenesis and may help in identifying an effective therapeutic strategy.

Diagnostic Accuracy of a Novel On-site Virtual Fractional Flow Reserve Parallel Computing System.

PURPOSE: To evaluate the diagnostic accuracy of a novel on-site virtual fractional flow reserve (vFFR) derived from coronary computed tomography angiography (CTA). MATERIALS AND METHODS: We analyzed 100 vessels from 57 patients who had undergone CTA followed by invasive FFR during coronary angiography. Coronary lumen segmentation and three-dimensional reconstruction were conducted using a completely automated algorithm, and parallel computing based vFFR prediction was performed. Lesion-specific ischemia based on FFR was defined as significant at ≤0.8, as well as ≤0.75, and obstructive CTA stenosis was defined that ≥50%. The diagnostic performance of vFFR was compared to invasive FFR at both ≤0.8 and ≤0.75. RESULTS: The average computation time was 12 minutes per patient. The correlation coefficient (r) between vFFR and invasive FFR was 0.75 [95% confidence interval (CI) 0.65 to 0.83], and Bland-Altman analysis showed a mean bias of 0.005 (95% CI -0.011 to 0.021) with 95% limits of agreement of -0.16 to 0.17 between vFFR and FFR. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 78.0%, 87.1%, 72.5%, 58.7%, and 92.6%, respectively, using the FFR cutoff of 0.80. They were 87.0%, 95.0%, 80.0%, 54.3%, and 98.5%, respectively, with the FFR cutoff of 0.75. The area under the receiver-operating characteristics curve of vFFR versus obstructive CTA stenosis was 0.88 versus 0.61 for the FFR cutoff of 0.80, respectively; it was 0.94 versus 0.62 for the FFR cutoff of 0.75. CONCLUSION: Our novel, fully automated, on-site vFFR technology showed excellent diagnostic performance for the detection of lesion-specific ischemia.