Parathormone levels add prognostic ability to N-terminal pro-brain natriuretic peptide in stable coronary patients

Aims: There are controversial data on the ability of the components of mineral metabolism (vitamin D, phosphate, parathormone [PTH], fibroblast growth factor-23 [FGF23], and klotho) to predict cardiovascular events. In addition, it is unknown whether they add any prognostic value to other well-known biomarkers. Methods and results: In 969 stable coronary patients, we determined plasma levels of all the aforementioned components of mineral metabolism with a complete set of clinical and biochemical variables, including N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hs-TnI), and high-sensitivity C-reactive protein. Secondary outcomes were ischaemic events (any acute coronary syndrome, stroke, or transient ischaemic attack) and heart failure or death. The primary outcome was a composite of the secondary outcomes. Median follow-up was 5.39 years. Age was 60 (52–72) years. Median glomerular filtration rate was 80.4 (65.3–93.1) mL/min/1.73 m2. One-hundred and eighty-five patients developed the primary outcome. FGF23, PTH, hs-TnI, and NT-proBNP were directly related with the primary outcome on univariate Cox analysis, while Klotho and calcidiol were inversely related. On multivariate analysis, only PTH (HR 1.058 [CI 1.021–1.097]; P = 0.002) and NT-proBNP (HR 1.020 [CI 1.012–1.028]; P 85.5 RU/mL) (P < 0.001) but not in patients with low FGF23 levels (P = 0.551). There was a significant interaction between FGF23 and PTH (P = 0.002). However, there was no significant interaction between PTH and both klotho and calcidiol levels. Conclusions: Parathormone is an independent predictor of cardiovascular events in coronary patients, adding complimentary prognostic information to NT-proBNP plasma levels. This predictive value is restricted to patients with high FGF23 plasma levels. This should be considered in the design of future studies in this field.This work was supported by grants from Instituto de Salud Carlos III (ISCIII) and Fondos FEDER (Fondo Europeo de Desarrollo Regional) European Union (PI05/0451, PI14/1567, PI17/01615, and PI17/01495); Spanish Society of Cardiology; Spanish Society of Arteriosclerosis; RECAVA (Red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares) (RD06/0014/0035); and Instituto de Salud Carlos III FEDER (FJD biobank: RD09/0076/00101). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

Important abnormalities of bone mineral metabolism are present in patients with coronary artery disease with a mild decrease of the estimated glomerular filtration rate

The final publication is avilable at: Journal of Bone and Mineral Metabolism 30.9 (2015): 1-34Chronic kidney disease (CKD)–mineral and bone disorder (MBD) is characterized by increased circulating levels of parathormone (PTH) and fibroblast growth factor 23 (FGF23), bone disease, and vascular calcification, and is associated with adverse outcomes. We studied the prevalence of mineral metabolism disorders, and the potential relationship between decreased estimated glomerular filtration rate (eGFR) and CKD-MBD in coronary artery disease patients in a cross-sectional study of 704 outpatients 7.5 ± 3.0 months after an acute coronary syndrome. The mean eGFR (CKD Epidemiology Collaboration formula) was 75.8 ± 19.1 ml/min/1.73 m2. Our patients showed lower calcidiol plasma levels than a healthy cohort from the same geographical area. In the case of men, this finding was present despite similar creatinine levels in both groups and older age of the healthy subjects. Most patients (75.6 %) had an eGFR below 90 ml/min/1.73 m2 (eGFR categories G2–G5), with 55.3 % of patients exhibiting values of 60–89 ml/min/1.73 m2 (G2). PTH (r = −0.3329, p < 0.0001) and FGF23 (r = −0.3641, p < 0.0001) levels inversely correlated with eGFR, whereas calcidiol levels and serum phosphate levels did not. Overall, PTH levels were above normal in 34.9 % of patients. This proportion increased from 19.4 % in G1 category patients, to 33.7 % in G2 category patients and 56.6 % in G3–G5 category patients (p < 0.001). In multivariate analysis, eGFR and calcidiol levels were the main independent determinants of serum PTH. The mean FGF23 levels were 69.9 (54.6–96.2) relative units (RU)/ml, and 33.2 % of patients had FGF23 levels above 85.5 RU/ml (18.4 % in G1 category patients, 30.0 % in G2 category patients, and 59.2 % in G3–G5 category patients; p < 0.001). In multivariate analysis, eGFR was the main predictor of FGF23 levels. Increased phosphate levels were present in 0.7 % of the whole sample: 0 % in G1 category patients, 0.3 % in G2 category patients, and 2.8 % in G3–G5 category patients (p = 0.011). Almost 90 % of patients had calcidiol insufficiency without significant differences among the different degrees of eGFR. In conclusion, in patients with coronary artery disease there is a large prevalence of increased FGF23 and PTH levels. These findings have an independent relationship with decreased eGFR, and are evident at an eGFR of 60–89 ml/min/1.73 m2. Then, mild decreases in eGFR must be taken in consideration by the clinician because they are associated with progressive abnormalities of mineral metabolismFondo de Investigaciones Sanitarias (PI10/00072, PI14/00386, PIE13/00051, PI05/0451, PI05/1497, PI05/52475, PI05/1043, PS09/01405, PI14/1567) y FRIAT, Spanish Society of Cardiology, Spanish Heart Foundation, Spanish Society of Arteriosclerosis, REDINREN (RD012/0021), Biobank grants from Instituto de Salud Carlos III FEDER, RD09/0076/00101 (FJD Biobank) and Abbvie Laboratories. PN I+D+I 2008-2011 and ISCIII co-financed by FEDER, CIBERDEM and e-PREDIC

Singlet oxygen triggers chloroplast rupture and cell death in the zeaxanthin epoxidase defective mutant aba1 of Arabidopsis thaliana under high light stress

[EN] The two Arabidopsis thaliana mutants, aba1 and max4, were previously identified as sharing a number of coregulated genes with both the flu mutant and Arabidopsis cell suspension cultures exposed to high light (HL). On this basis, we investigated whether aba1 and max4 were generating high amounts of singlet oxygen (1O2) and activating 1O2-mediated cell death. Thylakoids of aba1 produced twice as much 1O2 as thylakoids of max4 and wild type (WT) plants when illuminated with strong red light. 1O2 was measured using the spin probe 2,2,6,6-tetramethyl-4-piperidone hydrochloride. 77-K chlorophyll fluorescence emission spectra of thylakoids revealed lower aggregation of the light harvesting complex II in aba1. This was rationalized as a loss of connectivity between photosystem II (PSII) units and as the main cause for the high yield of 1O2 generation in aba1. Upregulation of the 1O2 responsive gene AAA-ATPase was only observed with statistical significant in aba1 under HL. Two early jasmonate (JA)-responsive genes, JAZ1 and JAZ5, encoding for two repressor proteins involved in the negative feedback regulation of JA signalling, were not up-regulated to the WT plant levels. Chloroplast aggregation followed by chloroplast rupture and eventual cell death was observed by confocal imaging of the fluorescence emission of leaf cells of transgenic aba1 plants expressing the chimeric fusion protein SSU-GFP. Cell death was not associated with direct 1O2 cytotoxicity in aba1, but rather with a delayed stress response. In contrast, max4 did not show evidence of 1O2-mediated cell death. In conclusion, aba1 may serve as an alternative model to other 1O2-overproducing mutants of Arabidopsis for investigating 1O2-mediated cell death

Mcp-1 predicts recurrent cardiovascular events in patients with persistent inflammation

Clinical data indicate that patients with C-reactive protein (CRP) levels higher than 2 mg per liter suffer from persistent inflammation, which is associated with high risk of cardiovascular disease (CVD). We determined whether a panel of biomarkers associated with CVD could predict recurrent events in patients with low or persistent inflammation and coronary artery disease (CAD). We followed 917 patients with CAD (median 4.59 ± 2.39 years), assessing CRP, galectin-3, monocyte chemoattractant protein-1 (MCP-1), N-terminal fragment of brain natriuretic peptide (NT-proBNP) and troponin-I plasma levels. The primary outcome was the combination of cardiovascular events (acute coronary syndrome, stroke or transient ischemic event, heart failure or death). Patients with persistent inflammation (n = 343) showed higher NT-proBNP and MCP-1 plasma levels compared to patients with CRP &lt; 2 mg/L. Neither MCP-1 nor NT-proBNP was associated with primary outcome in patients with CRP &lt; 2 mg/L. However, NT-proBNP and MCP-1 plasma levels were associated with increased risk of the primary outcome in patients with persistent inflammation. When patients were divided by type of event, MCP-1 was associated with an increased risk of acute ischemic events. A significant interaction between MCP-1 and persistent inflammation was found (synergy index: 6.17 (4.39–7.95)). In conclusion, MCP-1 plasma concentration is associated with recurrent cardiovascular events in patients with persistent inflammation.This research was funded by grants from Fondo de Investigaciones Sanitarias (PI14/1567, PI05/0451, PI16/01419, PI17/01615, PI17/01495, PI19/00128); RETOS-Colaboración (RTC2019-006826-1); Spanish Society of Arteriosclerosis; and Instituto de Salud Carlos III FEDER (FJD biobank: RD09/0076/00101

Salivary DNA Methylation as an Epigenetic Biomarker for Head and Neck Cancer. Part I: A Diagnostic Accuracy Meta-Analysis

DNA hypermethylation is an important epigenetic mechanism for gene expression inactivation in head and neck cancer (HNC). Saliva has emerged as a novel liquid biopsy representing a potential source of biomarkers. We performed a comprehensive meta-analysis to evaluate the overall diagnostic accuracy of salivary DNA methylation for detecting HNC. PubMed EMBASE, Web of Science, LILACS, and the Cochrane Library were searched. Study quality was assessed by the Quality Assessment for Studies of Diagnostic Accuracy-2, and sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (dOR), and their corresponding 95% confidence intervals (CIs) were calculated using a bivariate random-effect meta-analysis model. Meta-regression and subgroup analyses were performed to assess heterogeneity. Eighty-four study units from 18 articles with 8368 subjects were included. The pooled sensitivity and specificity of salivary DNA methylation were 0.39 and 0.87, respectively, while PLR and NLR were 3.68 and 0.63, respectively. The overall area under the curve (AUC) was 0.81 and the dOR was 8.34. The combination of methylated genes showed higher diagnostic accuracy (AUC, 0.92 and dOR, 36.97) than individual gene analysis (AUC, 0.77 and dOR, 6.02). These findings provide evidence regarding the potential clinical application of salivary DNA methylation for HNC diagnosisThis work was co-funded by the Instituto de Salud Carlos III (ISCIII) (PI20/01449) and the European Regional Development Fund (FEDER). A.D.-L. is funded by a “Juan Rodés” contract from ISCIII (JR17/00016). L.M.-R. is funded by a “Miguel Servet” contract from ISCIII (CP20/00129)S

The role of bioimpedance analysis in overweight and obese patients with acute heart failure: a pilot study.

AIMS Residual congestion at the time of hospital discharge is an important readmission risk factor, and its detection with physical examination and usual diagnostic techniques have strong limitations in overweight and obese patients. New tools like bioelectrical impedance analysis (BIA) could help to determine when euvolaemia is reached. The aim of this study was to investigate the usefulness of BIA in management of heart failure (HF) in overweight and obese patients. METHODS AND RESULTS Our study is a single-centre, single-blind, randomized controlled trial that included 48 overweight and obese patients admitted for acute HF. The study population was randomized into two arms: BIA-guided group and standard care. Serum electrolytes, kidney function, and natriuretic peptides were followed up during their hospital stay and at 90 days after discharge. The primary endpoint was development of severe acute kidney injury (AKI) defined as an increase in serum creatinine by >0.5 mg/dL during hospitalization, and the main secondary endpoint was the reduction of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels during hospitalization and within 90 days after discharge. The BIA-guided group showed a remarkable lower incidence of severe AKI, although no significant differences were found (41.4% vs. 16.7%; P = 0.057). The proportion of patients who achieved levels of NT-proBNP < 1000 pg/mL at 90 days was significantly higher in the BIA-guided group than in the standard group (58.8% vs. 25%; P = 0.049). No differences were observed in the incidence of adverse outcomes at 90 days. CONCLUSIONS Among overweight and obese patients with HF, BIA reduces NT-proBNP levels at 90 days compared with standard care. In addition, there is a trend towards lower incidence of AKI in the BIA-guided group. Although more studies are required, BIA could be a useful tool in decompensated HF management in overweight and obese patients.This research received no external funding.S

2023 26th Conference on Innovation in Clouds, Internet and Networks and Workshops (ICIN)

Network Slicing (NS) is a key enabler of the 5G network ecosystem due to its potential to provide distinct services over the same physical infrastructure. However, the necessity to optimally orchestrate resources for heterogeneous demands is crucial when dealing with resource constraints and Quality-of-Service (QoS) requirements. We consider a radio access network scenario providing NS over multiple base stations (BS) with limited resources, and we design an efficient resource orchestration technique, based on reinforcement learning, which optimizes resource utilization among different services while satisfying the constraints and complying with Service Level Agreement (SLA) and QoS requirements. The proposed technique makes use of the Trust Region Method to formulate the orchestration objective function and satisfy the constraints and is then optimized via Kronecker Factored Approximate Curvature (K-FAC). Extensive simulations demonstrate that the proposed technique outperforms other Reinforcement Learning (RL) algorithms, reaching 99% of QoS and SLA satisfaction while assuring bandwidth constraints.EU H2020 MSCA ITN-ETN IoTalentum (grant no. 953442)Consejería de Educación de la Junta de Castilla y León y FEDER (VA231P20)Ministerio de Ciencia e Innovación y Agencia Estatal de Investigación (Proyecto PID2020-112675RB-C42 financiado por MCIN/AEI/10.13039/501100011033

Monocyte chemoattractant protein-1 Is an independent predictor of coronary artery ectasia in patients with acute coronary syndrome

Our purpose was to assess a possible association of inflammatory, lipid and mineral metabolism biomarkers with coronary artery ectasia (CAE) and to determine a possible association of this with acute atherotrombotic events (AAT).We studied 270 patients who underwent coronary angiography during an acute coronary syndrome 6 months before. Plasma levels of several biomarkers were assessed, and patients were followed during a median of 5.35 (3.88–6.65) years. Two interventional cardiologists reviewed the coronary angiograms, diagnosing CAE according to previously published criteria in 23 patients (8.5%). Multivariate binary logistic regression analysis was used to search for independent predictors of CAE. Multivariate analysis revealed that, aside from gender and a diagnosis of dyslipidemia, only monocyte chemoattractant protein-1 (MCP-1) (OR = 2.25, 95%CI = (1.35–3.76) for each increase of 100 pg/mL, p = 0.001) was independent predictor of CAE, whereas mineral metabolism markers or proprotein convertase subtilisin/kexin type 9 were not. Moreover, CAE was a strong predictor of AAT during follow-up after adjustment for other clinically relevant variables (HR = 2.67, 95%CI = (1.22–5.82), p = 0.013). This is the first report showing that MCP-1 is an independent predictor of CAE, suggesting that CAE and coronary artery disease may share pathogenic mechanisms. Furthermore, CAE was associated with an increased incidence of AATThis work was supported by grants from the following: Fondo de Investigaciones Sanitarias (PI05/0451, PI05/1497, PI05/52475, PI05/1043, PS09/01405, and PI10/00072, PI14/01567, PI17/01615): http://www.isciii.es/ISCIII/ es/contenidos/fd-investigacion/fd-financiacion/convocatorias-ayudas-accion-estrategica-salud.shtml; Spanish Society of Cardiology; Spanish Heart Foundation. http://www.secardiologia.es/; Spanish Society of Arteriosclerosis.www.searteriosclerosis.org; CiberCV. http://www.cibercv.es/; RECAVA (RD06/0014/0035); www.recava.com; Fundación Lilly. https://www.lilly.es/nuestra-compania/fundacion-lilly-folder; Instituto de Salud Carlos III FEDER (FJD biobank: RD09/0076/00101); http://www.isciii.es/; and AbbVie Laboratories. http://www.abbvie.es/

Differential profile in inflammatory and mineral metabolism biomarkers in patients with ischemic heart disease without classical coronary risk factors

AbstractBackgroundPatients with coronary heart disease (CHD) without classical cardiovascular risk factors (CRFs) are uncommon, and their profile has not been thoroughly studied. In CHD patients, we have assessed the differences in several biomarkers between those with and without CRF.MethodsWe studied 704 patients with CHD, analyzing plasma levels of biomarkers related to inflammation, thrombosis, renal damage, and heart failure: high-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1), galectin-3, N-terminal fragment of brain natriuretic peptide (NT-pro-BNP), calcidiol (vitamin D metabolite), fibroblast growth factor-23 (FGF-23), parathormone, and phosphate.ResultsTwenty patients (2.8%) exhibited no CRFs. Clinical variables were well balanced in both groups, with the logical exceptions of no use of antidiabetic drugs, lower triglyceride and glucose, and higher high-density lipoprotein cholesterol in no-CRF patients.No-CRF patients showed lower hs-CRP (2.574±3.120 vs. 4.554±9.786mg/L; p=0.018), MCP-1 (114.75±36.29 vs. 143.56±65.37pg/ml; p=0.003), and FGF-23 (79.28±40.22 vs. 105.17±156.61RU/ml; p=0.024), and higher calcidiol (23.66±9.12 vs. 19.49±8.18ng/ml; p=0.025) levels. At follow-up, 10.0% vs. 11.0% patients experienced acute ischemic event, heart failure, or death in the non-CRF and CRF groups, respectively (p=0.815, log-rank test). The limited number of non-CRF patients may have influenced this finding. A Cox regression analysis in the whole population showed that high calcidiol, and low MCP-1 and FGF-23 plasma levels are associated with a better prognosis.ConclusionsCHD patients without CRFs show a favorable biomarker profile in terms of inflammation and mineral metabolism. Further studies are needed to investigate whether this difference translates into a better prognosis

Millimeter-wave channel measurements and path loss characterization in a typical indoor office environment

In this paper, a path loss characterization at millimeter-wave (mmWave) frequencies is performed in a typical indoor office environment. Path loss results were derived from propagation channel measurements collected in the 25–40 GHz frequency band, in both line-of-sight (LOS) and obstructed-LOS (OLOS) propagation conditions. The channel measurements were performed using a frequency-domain channel sounder, which integrates an amplified radio over fiber (RoF) link to avoid the high losses at mmWave. The path loss was analyzed in the 26 GHz, 28 GHz, 33 GHz and 38 GHz frequency bands through the close-in free space reference distance (CI) and the floating-intercept (FI) models. These models take into account the distance dependence of the path loss for a single frequency. Nevertheless, to jointly study the distance and frequency dependence of the path loss, multi-frequency models were considered. The parameters of the ABG (A-alpha, B-beta and G-gamma) and the close-in free space reference distance with frequency path loss exponent (CIF) models were derived from the channel measurements in the whole 25–40 GHz band under the minimum mean square error (MMSE) approach. The results show that, in general, there is some relationship between the model parameters and the frequency. Path loss exponent (PLE) values smaller than the theoretical free space propagation were obtained, showing that there are a waveguide effect and a constructive interference of multipath components (MPCs). Since the measurements were obtained in the same environment and with the same configuration and measurement setup, it is possible to establish realistic comparisons between the model parameters and the propagation behavior at the different frequencies considered. The results provided here allow us to have a better knowledge of the propagation at mmWave frequencies and may be of interest to other researchers in the simulation and performance evaluation of future wireless communication systems in indoor hotspot environments.This work has been funded in part by the MCIN/AEI/10.13039/501100011033/ through the I+D+i Project under Grant PID2020-119173RB-C21 and Grant PID2020-119173RB-C22, and by COLCIENCIAS in Colombia