Development of a new detection algorithm to identify acute coronary syndrome using electrochemical biosensors for real-world long-term monitoring

Electrochemically based technologies are rapidly moving from the laboratory to bedside applications and wearable devices, like in the field of cardiovascular disease. Major efforts have focused on the biosensor component in contrast with those employed in creating more suitable detection algorithms for long-term real-world monitoring solutions. The calibration curve procedure presents major limitations in this context. The objective is to propose a new algorithm, compliant with current clinical guidelines, which can overcome these limitations and contribute to the development of trustworthy wearable or telemonitoring solutions for home-based care. A total of 123 samples of phosphate buffer solution were spiked with different concentrations of troponin, the gold standard method for the diagnosis of the acute coronary syndrome. These were classified as normal or abnormal according to established clinical cut-off values. Off-the-shelf screen-printed electrochemical sensors and cyclic voltammetry measurements (sweep between −1 and 1 V in a 5 mV step) was performed to characterize the changes on the surface of the biosensor and to measure the concentration of troponin in each sample. A logistic regression model was developed to accurately classify these samples as normal or abnormal. The model presents high predictive performance according to specificity (94%), sensitivity (92%), precision (92%), recall (92%), negative predictive value (94%) and F-score (92%). The area under the curve of the precision-recall curve is 97% and the positive and negative likelihood ratios are 16.38 and 0.082, respectively. Moreover, high discriminative power is observed from the discriminate odd ratio (201) and the Youden index (0.866) values. The promising performance of the proposed algorithm suggests its capability to overcome the limitations of the calibration curve procedure and therefore its suitability for the development of trustworthy home-based care solutions

A review of biophysiological and biochemical indicators of stress for connected and preventive healthcare

Stress is a known contributor to several life-threatening medical conditions and a risk factor for triggering acute cardiovascular events, as well as a root cause of several social problems. The burden of stress is increasing globally and, with that, is the interest in developing effective stress-monitoring solutions for preventive and connected health, particularly with the help of wearable sensing technologies. The recent development of miniaturized and flexible biosensors has enabled the development of connected wearable solutions to monitor stress and intervene in time to prevent the progression of stress-induced medical conditions. This paper presents a review of the literature on different physiological and chemical indicators of stress, which are commonly used for quantitative assessment of stress, and the associated sensing technologies

Cardiovascular fitness in youth: association with obesity and metabolic abnormalities.

Therapies currently implemented for obesity are focused on nutritional aspects and on physical activity. In order to make physical activity a positive therapy instead of triggering disabilities it is relevant to accurately assess cardiovascular fitness. Objective: To assess the cardiovascular fitness by measuring the peak oxygen consumption and to asses their relationship with classical cardiometabolic parameters. Methods: A modified Balke protocol was applied to one hundred and twenty-six Caucasians (60% males),ranging between 9 and 16 years old, who underwent an assessment of obesity. The non-obese group consisted of healthy age and sex matched subjects who were invited to participate from the general population. Results: Significant differences in consumption of oxygen peak between non-obese and obese individuals were observed. In contrast, no significant differences existed between the categories of obesity. Furthermore in obese subjects consumption of oxygen peak was inversely correlated with parameters of cardiometabolic risk,particularly insulin and HOMA index. In addition, two predictive equations of consumption of oxygen peak, with an R2 of 0.74 and 0.84, respectively, have been developed. Conclusion: The consumption of oxygen peak is a relevant clinical parameter that should be included in the routine clinical assessment of obese subjects. Therefore, it is crucial to make exercise tests more affordable which can be achieved by employing predictive equations Las terapias que se implantan actualmente para la obesidad se centran en los aspectos nutricionales y sobre la actividad física. Con el fin de hacer que la actividad física sea una terapia positiva en vez de un desencadenador de discapacidades, es relevante evaluar de forma precisa el entrenamiento cardiovascular. Objetivo: evaluar el entrenamiento cardiovascular midiendo el consumo máximo de oxígeno y evaluar su relación con los parámetros cardiometabólicos clásicos. Métodos: se aplicó el protocolo modificado de Balke a 126 individuos caucásicos (60 % de varones), con edades entre 9 y 16 años, que se sometieron a una evaluación de obesidad. El grupo de no obesos consistía de individuos sanos, de la población general, emparejados por edad y sexo y a los que se les invitó a participar. Resultados: se observaron diferencias significativas en el consumo máximo de oxígeno entre los indiviudos obesos y no obesos. Por contra, no existían diferencias significativas entre las categorías de obesidad. Además, en los sujetos obesos, el consumo máximo de oxígeno se correlacionó de forma inversa con los parámetros de riesgo cardiometabólico, particularmente con la insulina y el índice HOMA. Además, se han desarrollado dos ecuaciones predictivas del consumo máximo de oxígeno con una R2 de 0,74 y de 0,84, respectivamente. Conclusión: el consumo máximo de oxígeno es un parámetro clínico relevante que debería incluirse en la evaluación clínica rutinaria de los sujetos obesos. Por lo tanto, es crucial hacer que las pruebas de esfuerzo sean más asequibles, que puedan alcanzarse empleando las ecuaciones predictivas

Longitudinal genome-wide DNA methylation analysis uncovers persistent early-life DNA methylation changes

BACKGROUND: Early life is a period of drastic epigenetic remodeling in which the epigenome is especially sensitive to extrinsic and intrinsic influence. However, the epigenome-wide dynamics of the DNA methylation changes that occur during this period have not been sufficiently characterized in longitudinal studies. METHODS: To this end, we studied the DNA methylation status of more than 750,000 CpG sites using Illumina MethylationEPIC arrays on 33 paired blood samples from 11 subjects at birth and at 5 and 10 years of age, then characterized the chromatin context associated with these loci by integrating our data with histone, chromatin-state and enhancer-element external datasets, and, finally, validated our results through bisulfite pyrosequencing in two independent longitudinal cohorts of 18 additional subjects. RESULTS: We found abundant DNA methylation changes (110,726 CpG sites) during the first lustrum of life, while far fewer alterations were observed in the subsequent 5 years (460 CpG sites). However, our analysis revealed persistent DNA methylation changes at 240 CpG sites, indicating that there are genomic locations of considerable epigenetic change beyond immediate birth. The chromatin context of hypermethylation changes was associated with repressive genomic locations and genes with developmental and cell signaling functions, while hypomethylation changes were linked to enhancer regions and genes with immunological and mRNA and protein metabolism functions. Significantly, our results show that genes that suffer simultaneous hyper- and hypomethylation are functionally distinct from exclusively hyper- or hypomethylated genes, and that enhancer-associated methylation is different in hyper- and hypomethylation scenarios, with hypomethylation being more associated to epigenetic changes at blood tissue-specific enhancer elements. CONCLUSIONS: These data show that epigenetic remodeling is dramatically reduced after the first 5 years of life. However, there are certain loci which continue to manifest DNA methylation changes, pointing towards a possible functionality beyond early development. Furthermore, our results deepen the understanding of the genomic context associated to hyper- or hypomethylation alterations during time, suggesting that hypomethylation of blood tissue-specific enhancer elements could be of importance in the establishment of functional states in blood tissue during early-life

Longitudinal study of DNA methylation during the first 5 years of life.

Background: Early life epigenetic programming influences adult health outcomes. Moreover, DNA methylation levels have been found to change more rapidly during the first years of life. Our aim was the identification and characterization of the CpG sites that are modified with time during the first years of life. We hypothesize that these DNA methylation changes would lead to the detection of genes that might be epigenetically modulated by environmental factors during early childhood and which, if disturbed, might contribute to susceptibility to diseases later in life. Methods: The study of the DNA methylation pattern of 485577 CpG sites was performed on 30 blood samples from 15 subjects, collected both at birth and at 5 years old, using Illumina® Infinium 450 k array. To identify differentially methylated CpG (dmCpG) sites, the methylation status of each probe was examined using linear models and the Empirical Bayes Moderated t test implemented in the limma package of R/Bioconductor. Surogate variable analysis was used to account for batch effects. Results: DNA methylation levels significantly changed from birth to 5 years of age in 6641 CpG sites. Of these, 36.79 % were hypermethylated and were associated with genes related mainly to developmental ontology terms, while 63.21 % were hypomethylated probes and associated with genes related to immune function. Conclusions: Our results suggest that DNA methylation alterations with age during the first years of life might play a significant role in development and the regulation of leukocyte-specific functions. This supports the idea that blood leukocytes experience genome remodeling related to their interaction with environmental factors, underlining the importance of environmental exposures during the first years of life and suggesting that new strategies should be take into consideration for disease prevention

Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as novel risk factors for Alzheimers Disease

The genetic component of Alzheimer’s disease (AD) has been mainly assessed using Genome Wide Association Studies (GWAS), which do not capture the risk contributed by rare variants. Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals —16,036 AD cases and 16,522 controls— in a two-stage analysis. Next to known genes TREM2, SORL1 and ABCA7, we observed a significant association of rare, predicted damaging variants in ATP8B4 and ABCA1 with AD risk, and a suggestive signal in ADAM10. Next to these genes, the rare variant burden in RIN3, CLU, ZCWPW1 and ACE highlighted these genes as potential driver genes in AD-GWAS loci. Rare damaging variants in these genes, and in particular loss-of-function variants, have a large effect on AD-risk, and they are enriched in early onset AD cases. The newly identified AD-associated genes provide additional evidence for a major role for APP-processing, Aβ-aggregation, lipid metabolism and microglial function in AD

Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer’s disease

Alzheimer’s disease (AD), the leading cause of dementia, has an estimated heritability of approximately 70%1. The genetic component of AD has been mainly assessed using genome-wide association studies, which do not capture the risk contributed by rare variants2. Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals—16,036 AD cases and 16,522 controls. Next to variants in TREM2, SORL1 and ABCA7, we observed a significant association of rare, predicted damaging variants in ATP8B4 and ABCA1 with AD risk, and a suggestive signal in ADAM10. Additionally, the rare-variant burden in RIN3, CLU, ZCWPW1 and ACE highlighted these genes as potential drivers of respective AD-genome-wide association study loci. Variants associated with the strongest effect on AD risk, in particular loss-of-function variants, are enriched in early-onset AD cases. Our results provide additional evidence for a major role for amyloid-β precursor protein processing, amyloid-β aggregation, lipid metabolism and microglial function in AD

Anàlisi, disseny i implementació d'un gestor per facilitar la feina d'agrupar i desagrupar productes a Mango

Actualmente en Mango se realizan gran parte de acciones mediante el uso de gestores, subida de productos a la tienda online, consulta de información sobre productos, realización de acciones como bloqueos o devoluciones... Una funcionalidad que no existe actualmente es la de poder agrupar y desagrupar productos para que, a la hora de mostrarse en la tienda online, se pueda acceder fácilmente a sus tallas y colores. La funcionalidad mencionada anteriormente, se realiza manualmente a la hora de subir un producto a la tienda y si se produce alguna equivocación o en el futuro se quieren añadir nuevas tallas o colores se tiene que contactar a los empleados encargados de la gestión de la tienda online para que realicen la modificación de manera manual mediante accesos a la base de datos, un proceso que, aparte de ser tedioso, si se tienen que realizar muchos accesos de manera manual no hay manera de asegurar que no haya equivocaciones y, además, como se tiene que asignar a un empleado, o bien se retrasa la realización de la agrupación porque el empleado está ocupado o bien el empleado tiene que aplazar el trabajo que esté haciendo para realizar la agrupación. Este proyecto se basa en el análisis, diseño e implementación de una herramienta que permita facilitar la tarea de realizar agrupaciones y automatice el proceso, librando así a los empleados del sector online de realizar tareas tediosas y repetitivas y poder centrarse en tareas que aporten más valor a la empresa.Currently at Mango most functionalities are carried out with the use of managers, upload of products to the online store, inquiries about product information, execution of features such as blocking or refunds... A functionality that currently does not exist is the ability to group and ungroup products so that, when these need to be shown on the online store, their sizes and colors can be easily accessed. The functionality mentioned above is performed manually when a product is uploaded to the online store, and if a mistake is made or there is a future need to add sizes and/or colors, the employees tasked with the managing of the online store must be contacted so they can make the necessary modifications manually by accessing the database. A process which in addition to being tedious, lacks the capability of checking for errors when multiple manual accesses are required, and furthermore, because an employee must be assigned to the task, the completion of the process is either delayed because said employee is unavailable, or the employee has to put off whatever they were currently doing to carry out the grouping. This project is based on the analysis, design and implementation of a tool that improves the task of grouping and automates the process, freeing the online sector employees from tedious and repetitive tasks so they can focus on assignments which provide more value to the company

Uric acid is linked to cardiometabolic risk factors in overweight and obese youths

Objective:Observational studies have indicated that high levels of serum uric acid are associated with the risk of cardiovascular disease. The aim of the present study is to investigate the association of uric acid with individual cardiometabolic risk factors, as well as their degree of clustering, in overweight and moderate obese youth.Methods:Three hundred and thirty-three Caucasians of both sexes (149 women), from 5-18 years of age from those who underwent an assessment of overweight/obesity. Anthropometric parameters, office and 24-h blood pressure measurements and metabolic profile, including HDL-cholesterol, triglycerides, insulin, HOMA index and uric acid were assessed.Results:Uric acid was significantly higher in boys than in girls. A positive significant association between uric acid, and office, daytime and night-time SBP, insulin and triglycerides was observed. When boys and girls were grouped by sex-specific uric acid tertiles, a progressive increment was observed in BMI, BMI z-score and waist circumference as well as fasting insulin and HOMA index. In boys, this was also present in office and ambulatory SBP. Likewise, the number of abnormal metabolic risk factors also increases with the uric acid values and the higher the number of metabolic components the higher the uric acid values. Moreover, in a multiple regression analysis, uric acid was significantly related with male sex, waist circumference, both office and night-time SBP and birth weight.Conclusion:The present study found a positive association between uric acid and blood pressure, insulin and triglycerides. As uric acid levels increase there is a relevant clustering of metabolic risk factors, whereas elevated blood pressure is the risk factor less frequently present. Further studies need to assess the mechanistic link between uric acid and the cardiometabolic risk factors