Aging poses significant challenges to cardiovascular health necessitating novel therapeutic approaches. This study investigates the potential of the brown adipose tissue (BAT) derived lipokine 12,13-diHOME to mitigate age-induced impairments in cardiovascular function. Analysis of human and rodent plasma signaling lipids reveals a decline in 12,13-diHOME levels with age. Transplantation of BAT or sustained upregulation of 12,13-diHOME effectively preserved cardiac function in aged male and female mice. Bulk RNA-Seq of hearts from aged mice reveals significant increases in pathways involved in ER stress and fibrosis which were partially attenuated by BAT transplantation or sustained upregulation of 12,13-diHOME. Mechanistically, in vivo and in vitro models demonstrate that 12,13-diHOME alleviated ER stress through CaMKII inhibition, particularly in males. These findings underscore 12,13-diHOME as a promising candidate for combating age-related cardiovascular dysfunction, offering insights into potential therapeutic strategies for addressing cardiovascular diseases in aging populations.

BACKGROUND:The relative contribution of the different components of mechanical power to mortality is a subject of debate and has not been studied in COVID-19. The aim of this study is to evaluate both the total and the relative impact of each of the components of mechanical power on mortality in a well-characterized cohort of patients with COVID-19-induced acute respiratory failure undergoing invasive mechanical ventilation. This is a secondary analysis of the CIBERESUCICOVID project, a multicenter observational cohort study including fifty Spanish intensive care units that included COVID-19 mechanically ventilated patients between February 2020 and December 2021. We examined the association between mechanical power and its components (elastic static, elastic dynamic, total elastic and resistive power) with 90-day mortality after adjusting for confounders in seven hundred ninety-nine patients with COVID-19-induced respiratory failure undergoing invasive mechanical ventilation. RESULTS:At the initiation of mechanical ventilation, the PaO2/FiO2 ratio was 106 (78; 150), ventilatory ratio was 1.69 (1.40; 2.05), and respiratory system compliance was 35.7 (29.2; 44.5) ml/cmH2O. Mechanical power at the initiation of mechanical ventilation was 24.3 (18.9; 29.6) J/min, showing no significant changes after three days. In multivariable regression analyses, mechanical power and its components were not associated with 90-day mortality at the start of mechanical ventilation. After three days, total elastic and elastic static power were associated with higher 90-day mortality, but this relationship was also found for positive end-expiratory pressure. CONCLUSIONS:Neither mechanical power nor its components were independently associated with mortality in COVID-19-induced acute respiratory failure at the start of MV. Nevertheless, after three days, static elastic power and total elastic power were associated with lower odds of survival. Positive end-expiratory pressure and plateau pressure, however, captured this risk in a similar manner.

Given the vast and complex chemical search space, developing new techniques for identifying promising ligands that satisfy multiple objectives is highly desirable to reduce the costs and times required for effective drug discovery. Neural networks are frequently employed for this task, but they tend to generate molecules that are invalid both chemically and syntactically. As an alternative, metaheuristics have emerged as promising approaches, delivering notable results with reasonable computational costs. However, they often suffer from information loss during the process, leading to poor quality generations. In this work, we introduce a novel memetic algorithm that hybridizes Particle Swarm Optimization with Simulated Annealing. This approach aims to improve the balance between exploration and exploitation in the de-novo drug discovery process, ensuring that promising molecules are not overlooked during generation steps. We compare our approach against six state-of-the-art algorithms, and the results demonstrate that our algorithm enhances molecule generation quality, showing an increased diversity and improved chemical properties of the resulting ligands.

Introduction and objectives: There are scarce data on the factors associated with impaired functional status after transcatheter aortic valve replacement (TAVR) and its clinical impact. This study aimed to determine the incidence, predictors, and prognostic implications of impaired functional class (NYHA class III-IV) following TAVR. Methods: This multicenter study included 3462 transarterial TAVR patients receiving newer generation devices. The patients were compared according to their NYHA class at 1 month of follow-up (NYHA I-II vs NYHA III-IV). A multivariate logistic regression was performed to identify the predictors of 30-day NYHA class III-IV. Patient survival was compared with the Kaplan-Meier method and factors associated with decreased survival were identified with Cox regression analysis. Results: The mean age of the study population was 80.3 +/- 7.3 years, with 47% of women, and a median Society of Thoracic Surgeons score of 3.8% [IQR, 2.5-5.8]. A total of 208 patients (6%) were in NYHA class III-IV 1 month after TAVR. Predictors of 30-day NYHA class III-IV were baseline NYHA class III-IV (OR, 1.76; 95%CI, 1.08-2.89; P = .02), chronic pulmonary obstructive disease (OR, 1.80; 95%CI, 1.13-2.83; P = .01), and postTAVR severe mitral regurgitation (OR, 2.00; 95%CI, 1.21-3.31; P < .01). Patients in NYHA class III-IV 1 month after TAVR were at higher risk of death (HR, 3.68; 95%CI, 2.39-5.70; P < .01) and heart failure-related hospitalization (HR, 6.00; 95%CI, 3.76-9.60; P < .01) at 1-year follow-up. Conclusions: Up to 6% of contemporary TAVR patients exhibited an impaired functional status following TAVR. Worse baseline NYHA class, chronic pulmonary obstructive disease, and severe mitral regurgitation predicted 30-day NYHA class III/IV, and this determined a higher risk of mortality and heart failure hospitalization at 1-year follow-up. Further studies on the prevention and treatment optimization of patients with impaired functional status after TAVR are needed. (c) 2023 Sociedad Espanola de Cardiologia. Published by Elsevier Espana, S.L.U. All rights reserved.

We assessed aging hallmarks in skin, muscle, and adipose in the genetically diverse HET3 mouse, and generated a broad dataset comparing these to individual animal diagnostic SNPs from the 4 founding inbred strains of the HET3 line. For middle- and old-aged HET3 mice, we provided running wheel exercise to ensure our observations were not purely representative of sedentary animals, but age-related phenotypes were not improved with running wheel activity. Adipose tissue fibrosis, peripheral neuropathy, and loss of neuromuscular junction integrity were consistent phenotypes in older-aged HET3 mice regardless of physical activity, but aspects of these phenotypes were moderated by the SNP% contributions of the founding strains for the HET3 line. Taken together, the genetic contribution of founder strain SNPs moderated age-related phenotypes in skin and muscle innervation and were dependent on biological sex and chronological age. However, there was not a single founder strain (BALB/cJ, C57BL/6J, C3H/HeJ, DBA/2J) that appeared to drive more protection or disease-risk across aging in this mouse line, but genetic diversity in general was more protective.

Introducción y objetivos: Existen pocos datos acerca del impacto pronóstico de una clase funcional NYHA III-IV después del implante percutáneo de válvula aórtica (TAVI). El objetivo del estudio es determinar la incidencia, los predictores y las implicaciones pronósticas de una clase NYHA III-IV al mes del TAVI.Métodos: Estudio multicéntrico que incluyó a 3.462 pacientes sometidos a TAVI que recibieron dispositivos de nueva generación. Se comparó a los pacientes en clase funcional de la NYHA I-II con pacientes en NYHA III-IV al mes de seguimiento. Los predictores de clase NYHA III-IV a 1 mes se identificaron mediante regresión logística multivariante. La supervivencia se evaluó con el método de Kaplan-Meier y los factores asociados a peor pronóstico se identificaron mediante la regresión de Cox.Resultados: La edad media de la población de estudio era de 80,3 ± 7,3 años, con el 47% de mujeres y un valor mediano en la escala de la Society of Thoracic Surgeons del 3,8% [2,5-5,8]). Un total de 208 pacientes (6%) presentaron NYHA III-IV al mes del TAVI. Los predictores de NYHA III-IV al mes fueron: NYHA basal III-IV (OR = 1,76; IC95%, 1,08-2,89; p = 0,02), enfermedad pulmonar obstructiva crónica (OR = 1,80; IC95%, 1,13-2,83; p = 0,01) e insuficiencia mitral grave post-TAVI (OR = 2,00; IC95%, 1,21-3,31; p < 0,01). Los pacientes en NYHA III-IV al mes del TAVI tenían un mayor riesgo de muerte (HR = 3,68; IC95%, 2,39-5,70; p < 0,01) y hospitalización por insuficiencia cardiaca (HR = 6,00; IC95%, 3,76-9,60; p < 0,01) durante el año que siguió al TAVI.Conclusiones: El 6% de los pacientes presentaban un estado funcional deteriorado después del TAVI. Una peor clase NYHA basal, la enfermedad pulmonar obstructiva crónica y la insuficiencia mitral grave se asociaron a un mayor riesgo de presentar NYHA III-IV a los 30 días, lo que determinó un mayor riesgo de muerte y hospitalización por insuficiencia cardiaca al año de seguimiento. Se necesitan más estudios sobre la prevención y optimización del tratamiento de pacientes con deterioro del estado funcional después del TAVI.

Exercise mediates tissue metabolic function through direct and indirect adaptations to acylcarnitine (AC) metabolism, but the exact mechanisms are unclear. We found that circulating medium-chain acylcarnitines (AC) (C12-C16) are lower in active/endurance trained human subjects compared to sedentary controls, and this is correlated with elevated cardiorespiratory fitness and reduced adiposity. In mice, exercise reduced serum AC and increased liver AC, and this was accompanied by a marked increase in expression of genes involved in hepatic AC metabolism and mitochondrial β-oxidation. Primary hepatocytes from high-fat fed, exercise trained mice had increased basal respiration compared to hepatocytes from high-fat fed sedentary mice, which may be attributed to increased Ca2+ cycling and lipid uptake into mitochondria. The addition of specific medium- and long-chain AC to sedentary hepatocytes increased mitochondrial respiration, mirroring the exercise phenotype. These data indicate that AC redistribution is an exercise-induced mechanism to improve hepatic function and metabolism.

Due to the Internet of Things (IoT) widespread adoption, data traffic to cloud servers for analysis has surged, impacting IoT system latency. Fog Computing emerged as a solution, bringing processing capabilities closer to data generation points, reducing data sent to the cloud, and improving response times. However, it intensifies security concerns due to the proximity of sensitive data to users and limited node computational resources. This research aims to study encryption and data verification algorithms using various datasets and the cryptography software OpenSSL. Testing is performed on Raspberry Pi hardware, facilitating the implementation of Fog nodes. Metrics such as CPU, memory, and energy consumption are evaluated using scripts. Results show that data type does not influence algorithm choice, and patterns related to data size behaviour are identified, aiding in defining security strategies.

Background Acute coronary syndrome (ACS), specifically ST-segment elevation myocardial infarction is a major cause of morbidity and mortality throughout Europe. Diagnosis in the acute setting is mainly based on clinical symptoms and physician's interpretation of an electrocardiogram (ECG), which may be subject to errors. ST-segment elevation is the leading criteria to activate urgent reperfusion therapy, but a clear ST-elevation pattern might not be present in patients with coronary occlusion and ST-segment elevation might be seen in patients with normal coronary arteries. Methods The ASSIST project is a retrospective observational study aiming to improve the ECG-assisted assessment of ACS patients in the acute setting by incorporating an artificial intelligence platform, Willem™ to analyze 12‑lead ECGs. Our aim is to improve diagnostic accuracy and reduce treatment delays. ECG and clinical data collected during this study will enable the optimization and validation of Willem™. A retrospective multicenter study will collect ECG, clinical, and coronary angiography data from 10,309 patients. The primary outcome is the performance of this tool in the correct identification of acute myocardial infarction with coronary artery occlusion. Model performance will be evaluated internally with patients recruited in this retrospective study while external validation will be performed in a second stage. Conclusion ASSIST will provide key data to optimize Willem™ platform to detect myocardial infarction based on ECG-assessment alone. Our hypothesis is that such a diagnostic approach may reduce time delays, enhance diagnostic accuracy, and improve clinical outcomes.

The immense amount of data managed during the diagnosis process overwhelms, by far, the clinicians’ processing capabilities. Artificial intelligence methods like Multi-Layer Perceptrons come to help by providing a second opinion based on powerful and reliable data processing. Unfortunately, these methods often suffer from problems related to their training methods, which can lead to poor performance. Metaheuristics are promising training alternatives because of their stochastic and general-purpose nature. This work introduces a new training method based on metaheuristics, called Genetic Ant Lion Optimiser. It includes new features for dealing with the convergence problems of the original Ant Lion Optimiser and integrates a novel crossover operator for avoiding stagnation. Experiments compare our proposal against 31 state-of-the-art algorithms, over 20 different medical datasets. Classification quality metrics reflect that our approach attains a robust and efficient behaviour with the majority of the datasets, obtaining highlighted results, such as an accuracy of 1.0 with the kidney dataset (bi-class) and 0.943 with the lung-cancer dataset (multi-class). Besides, it reaches adequate convergence rates and reasonable time consumption.

Obesity and its co-morbidities including type 2 diabetes are increasing at epidemic rates in the U.S. and worldwide. Brown adipose tissue (BAT) is a potential therapeutic to combat obesity and type 2 diabetes. Increasing BAT mass by transplantation improves metabolic health in rodents, but its clinical translation remains a challenge. Here, we investigated if transplantation of 2-4 million differentiated brown pre-adipocytes from mouse BAT stromal fraction (SVF) or human pluripotent stem cells (hPSCs) could improve metabolic health. Transplantation of differentiated brown pre-adipocytes, termed ‘committed pre-adipocytes’ from BAT SVF from mice or derived from hPSCs improves glucose homeostasis and insulin sensitivity in recipient mice under conditions of diet-induced obesity, and this improvement is mediated through the collaborative actions of the liver transcriptome, tissue AKT signaling and FGF21. These data demonstrate that transplantation of a small number of brown adipocytes has significant long-term translational and therapeutic potential to improve glucose metabolism.

Brown adipose tissue (BAT) is correlated to cardiovascular health in rodents and humans, but the physiological role of BAT in the initial cardiac remodeling at the onset of stress is unknown. Activation of BAT via 48 h cold (16°C) in mice following transverse aortic constriction (TAC) reduced cardiac gene expression for LCFA uptake and oxidation in male mice and accelerated the onset of cardiac metabolic remodeling, with an early isoform shift of carnitine palmitoyltransferase 1 (CPT1) toward increased CPT1a, reduced entry of long chain fatty acid (LCFA) into oxidative metabolism (0.59 ± 0.02 vs. 0.72 ± 0.02 in RT TAC hearts, p < .05) and increased carbohydrate oxidation with altered glucose transporter content. BAT activation with TAC reduced early hypertrophic expression of β-MHC by 61% versus RT-TAC and reduced pro-fibrotic TGF-β1 and COL3α1 expression. While cardiac natriuretic peptide expression was yet to increase at only 3 days TAC, Nppa and Nppb expression were elevated in Cold TAC versus RT TAC hearts 2.7- and 2.4-fold, respectively. Eliminating BAT thermogenic activation with UCP1 KO mice eliminated differences between Cold TAC and RT TAC hearts, confirming effects of BAT activation rather than autonomous cardiac responses to cold. Female responses to BAT activation were blunted, with limited UCP1 changes with cold, partly due to already activated BAT in females at RT compared to thermoneutrality. These data reveal a previously unknown physiological mechanism of UCP1-dependent BAT activation in attenuating early cardiac hypertrophic and profibrotic signaling and accelerating remodeled metabolic activity in the heart at the onset of cardiac stress.

Background Acute respiratory distress syndrome (ARDS) can be classified into sub-phenotypes according to different inflammatory/clinical status. Prognostic enrichment was achieved by grouping patients into hypoinflammatory or hyperinflammatory sub-phenotypes, even though the time of analysis may change the classification according to treatment response or disease evolution. We aimed to evaluate when patients can be clustered in more than 1 group, and how they may change the clustering of patients using data of baseline or day 3, and the prognosis of patients according to their evolution by changing or not the cluster. Methods Multicenter, observational prospective, and retrospective study of patients admitted due to ARDS related to COVID-19 infection in Spain. Patients were grouped according to a clustering mixed-type data algorithm (k-prototypes) using continuous and categorical readily available variables at baseline and day 3. Results Of 6205 patients, 3743 (60%) were included in the study. According to silhouette analysis, patients were grouped in two clusters. At baseline, 1402 (37%) patients were included in cluster 1 and 2341(63%) in cluster 2. On day 3, 1557(42%) patients were included in cluster 1 and 2086 (57%) in cluster 2. The patients included in cluster 2 were older and more frequently hypertensive and had a higher prevalence of shock, organ dysfunction, inflammatory biomarkers, and worst respiratory indexes at both time points. The 90-day mortality was higher in cluster 2 at both clustering processes (43.8% [ n = 1025] versus 27.3% [ n = 383] at baseline, and 49% [ n = 1023] versus 20.6% [ n = 321] on day 3). Four hundred and fifty-eight (33%) patients clustered in the first group were clustered in the second group on day 3. In contrast, 638 (27%) patients clustered in the second group were clustered in the first group on day 3. Conclusions During the first days, patients can be clustered into two groups and the process of clustering patients may change as they continue to evolve. This means that despite a vast majority of patients remaining in the same cluster, a minority reaching 33% of patients analyzed may be re-categorized into different clusters based on their progress. Such changes can significantly impact their prognosis.

Autologous adipose tissue is commonly used for tissue engraftment for the purposes of soft tissue reconstruction due to its relative abundance in the human body and ease of acquisition using liposuction methods. This has led to the adoption of autologous adipose engraftment procedures that allow for the injection of adipose tissues to be used as a "filler" for correcting cosmetic defects and deformities in soft tissues. However, the clinical use of such methods has several limitations, including high resorption rates and poor cell survivability, which lead to low graft volume retention and inconsistent outcomes. Here, we describe a novel application of milled electrospun poly(lactic-co-glycolic acid) (PLGA) fibers, which can be co-injected with adipose tissue to improve engraftment outcomes. These PLGA fibers had no significant negative impact on the viability of adipocytes in vitro and did not elicit long-term proinflammatory responses in vivo. Furthermore, co-delivery of human adipose tissue with pulverized electrospun PLGA fibers led to significant improvements in reperfusion, vascularity, and retention of graft volume compared to injections of adipose tissue alone. Taken together, the use of milled electrospun fibers to enhance autologous adipose engraftment techniques represents a novel approach for improving upon the shortcomings of such methods.

Although the prevalence of community-acquired respiratory bacterial coinfection upon hospital admission in patients with coronavirus disease 2019 (COVID-19) has been reported to be < 5

INTRODUCTION:Critical COVID-19 survivors have a high risk of respiratory sequelae. Therefore, we aimed to identify key factors associated with altered lung function and CT scan abnormalities at a follow-up visit in a cohort of critical COVID-19 survivors. METHODS:Multicenter ambispective observational study in 52 Spanish intensive care units. Up to 1327 PCR-confirmed critical COVID-19 patients had sociodemographic, anthropometric, comorbidity and lifestyle characteristics collected at hospital admission; clinical and biological parameters throughout hospital stay; and, lung function and CT scan at a follow-up visit. RESULTS:The median [p25-p75] time from discharge to follow-up was 3.57 [2.77-4.92] months. Median age was 60 [53-67] years, 27.8% women. The mean (SD) percentage of predicted diffusing lung capacity for carbon monoxide (DLCO) at follow-up was 72.02 (18.33)% predicted, with 66% of patients having DLCO<80% and 24% having DLCO<60%. CT scan showed persistent pulmonary infiltrates, fibrotic lesions, and emphysema in 33%, 25% and 6% of patients, respectively. Key variables associated with DLCO<60% were chronic lung disease (CLD) (OR: 1.86 (1.18-2.92)), duration of invasive mechanical ventilation (IMV) (OR: 1.56 (1.37-1.77)), age (OR [per-1-SD] (95%CI): 1.39 (1.18-1.63)), urea (OR: 1.16 (0.97-1.39)) and estimated glomerular filtration rate at ICU admission (OR: 0.88 (0.73-1.06)). Bacterial pneumonia (1.62 (1.11-2.35)) and duration of ventilation (NIMV (1.23 (1.06-1.42), IMV (1.21 (1.01-1.45)) and prone positioning (1.17 (0.98-1.39)) were associated with fibrotic lesions. CONCLUSION:Age and CLD, reflecting patients' baseline vulnerability, and markers of COVID-19 severity, such as duration of IMV and renal failure, were key factors associated with impaired DLCO and CT abnormalities.

BACKGROUND The burden of cardiac death after transcatheter aortic valve replacement (TAVR), particularly from advanced heart failure (HF) and sudden cardiac death (SCD), remains largely unknown. OBJECTIVES This study sought to evaluate the incidence and predictors of SCD and HF-related death in TAVR recipients treated with newer-generation devices.METHODS This study included a total of 5,421 consecutive patients who underwent TAVR with newer-generation devices using balloon (75.7%) or self-expandable (24.3%) valves.RESULTS After a median follow-up of 2 (IQR: 1-3) years, 976 (18.0%) patients had died, 50.8% from cardiovascular causes. Advanced HF and SCD accounted for 11.6% and 7.5% of deaths, respectively. Independent predictors of HF-related death were atrial fibrillation (HR: 2.17; 95% CI: 1.47-3.22; P < 0.001), prior pacemaker (HR: 1.79; 95% CI: 1.10-2.92; P = 0.01), reduced left ventricular ejection fraction (HR: 1.08 per 5% decrease; 95% CI: 1.01-1.14; P = 0.02), transthoracic approach (HR: 2.50; 95% CI: 1.37-4.55; P = 0.003), and new-onset persistent left bundle branch block (HR: 1.85; 95% CI: 1.14-3.02; P = 0.01). Two baseline characteristics (diabetes, HR: 1.81; 95% CI: 1.13-2.89; P = 0.01; and chronic kidney disease, HR: 1.72; 95% CI: 1.02-2.90; P = 0.04) and 3 procedural findings (valve in valve, HR: 2.17; 95% CI: 1.01-4.64; P = 0.04; transarterial nontransfemoral approach, HR: 2.23; 95% CI: 1.23-4.48; P = 0.01; and periprocedural ventricular arrhythmia, HR: 7.19; 95% CI: 2.61-19.76; P < 0.001) were associated with an increased risk of SCD after TAVR.CONCLUSIONS Advanced HF and SCD accounted for a fifth of deaths after TAVR in contemporary practice. Potentially treatable factors leading to increased risk of HF deaths and SCD were identified, such as arrhythmia/ dyssynchrony factors for HF and valve-in-valve TAVR or periprocedural ventricular arrhythmias for SCD. (J Am Coll Cardiol Intv 2023;16:2277-2290) (c) 2023 by the American College of Cardiology Foundation.

Fast and precise medical diagnosis of human cancer is crucial for treatment decisions. Gene selection consists of identifying a set of informative genes from microarray data to allow high predictive accuracy in human cancer classification. This task is a combinatorial search problem, and optimisation methods can be applied for its resolution. In this paper, two memetic micro-genetic algorithms (MμV1 and MμV2) with different hybridisation approaches are proposed for feature selection of cancer microarray data. Seven gene expression datasets are used for experimentation. The comparison with stochastic state-of-the-art optimisation techniques concludes that problem-dependent local search methods combined with micro-genetic algorithms improve feature selection of cancer microarray data.

The use of electronic nicotine delivery systems, specifically electronic cigarettes (e-cig), has risen dramatically within the last few years; the demographic purchasing these devices is now predominantly adolescents that are not trying to quit the use of traditional combustible cigarettes, but rather are new users. The composition and appearance of these devices has changed since their first entry into the market in the late 2000s, but they remain composed of a battery and aerosol delivery system that is used to deliver breakdown products of propylene glycol/vegetable glycerin, flavorings, and potentially nicotine or other additives. Manufacturers have also adjusted the type of nicotine that is used within the liquid to make the inhalation more palatable for younger users, further affecting the number of youth who use these devices. Although the full spectrum of cardiovascular and cardiometabolic consequences of e-cig use is not fully appreciated, data is beginning to show that e-cigs can cause both short- and long-term issues on cardiac function, vascular integrity and cardiometabolic issues. This review will provide an overview of the cardiovascular, cardiometabolic, and vascular implications of the use of e-cigs, and the potential short- and long-term health effects. A robust understanding of these effects is important in order to inform policy makers on the dangers of e-cigs use.