El libro está estructurado como soporte de un curso de introducción al lenguaje C++. Todas las explicaciones van acompañadas de ejemplos, seguidos de ejecuciones que muestran la entrada/salida del ...ejemplo para afianzar los conceptos. Es aconsejable que el lector lea este libro delante del ordenador, para que al realizar y modificar los ejemplos comprenda mejor su funcionamiento. Además, al final de cada capítulo se proponen ejercicios de autoevaluación y de programación, todos ellos con sus correspondientes soluciones. La principal aportación de este libro, frente a otros libros similares, es que en él hemos querido reflejar los problemas a los que se enfrenta un lector cuando aprende un lenguaje de programación nuevo. La mayoría de los textos suponen que el lector no va a cometer errores, por lo que no hacen ninguna referencia a los posibles problemas de compilación del código o de comprensión de los conceptos explicados. Sin embargo, en este libro hemos optado por incluir algunos ejemplos con errores para mostrar los mensajes que genera el compilador. Sergio Luján Mora es Doctor Ingeniero en Informática por la Universidad de Alicante. Desde 1999 forma parte del Departamento de Lenguajes y Sistemas Informáticos de la Universidad de Alicante. Las asignaturas que imparte en la actualidad son "Programación en Internet" y "Programación y Estructuras de Datos". Ha escrito los libros "Programación en Internet: Clientes Web", "Programación de servidores web con CGI, SSI, e IDC", "Programación de aplicaciones web: historia, principios básicos y cliente web" y "Cuestionario básico sobre Programación en Internet".
Abstract
Background and Aims
The antiaging factor α-Klotho (KL) has been related to cardiovascular diseases (CVD), including coronary artery disease, heart failure and peripheral arterial disease. ...The soluble form of this protein (sKL), which is mainly produced by the kidneys, have demonstrated to display different protective effects on the cardiovascular system, e.g., prevention of vascular calcification, oxidative stress, or cardiac fibrosis. Likewise, different clinical studies have pointed out that CVD is a state of sKL deficiency, even when the renal function is still preserved. It has been demonstrated that peripheral blood circulating cells (PBCCs) also express KL, but little is known about its expression profile during CVD. The aim of this work is to determinate if the expression of KL gene and its promoter methylation in PBCCs are correlated with serum levels of the soluble protein, and if there exist any association with the underlying inflammatory process that occurs during CVD.
Method
Forty-four patients diagnosed with clinical atherosclerotic vascular disease (case group) and 15 subjects without CVD background (control group) were included in the study. Whole blood and serum samples were obtained from all participants. We performed gene expression analysis for KL expression in PBCCs by qPCR, as well as for DNMT1 and DNMT3A (members of the DNA-methyltransferases family), TNF, IL10 and NFKB1 (inflammatory parameters). We assessed the degree of methylation of the KL gene promoter in these cells by bisulfite sequencing. Furthermore, we determined circulating levels of sKL, TNFα and IL10 by ELISA immunoassay in serum samples of both groups.
Results
Results showed a lower expression of KL gene in PBCCs of patients with CVD compared to controls (45% reduction, P<0.001), which was accompanied by a higher degree of methylation of its promoter (36.7±6.3% vs. 15.9±4.8%, P<0.05). The case group also presented significantly higher levels of DNMT1 and DNMT3A transcripts in these cells (P<0.0001 for both), as well as higher values of proinflammatory parameters (gene expression of TNF and NFKB1, and TNF/IL10 ratio; P<0.001 for all of them). Serum levels of sKL were decreased in the CVD group compared to controls (a reduction of 57.5%, P<0.0001). KL expression in PBCCs correlated directly with systemic levels of sKL (r=0.20, P<0.05), but inversely with expression of DNMT1 (r=-0.33, P<0.01) and inflammatory parameters (r=-0.37, P<0.01 for NFKB1 expression; r=-0.38, P<0.01 for TNF/IL10 expression ratio; and r=-0.39, P<0.01 for serum TNFα/IL10 ratio). No significant associations were found between inflammatory markers and methylation degree of KL gene promoter.
Conclusion
These results indicate an association between epigenetic regulation of KL gene in PBCC and systemic levels of the soluble protein in CVD, which could be influenced by the proinflammatory state present in these disorders.
Abstract
Background and Aims
Atherosclerosis, a vascular pathological process with an important inflammatory component, underlies most of the cardiovascular diseases (CVD). Deficiencies in the ...antiaging factor α-Klotho (KL) have been related to the appearance and progression of atherosclerotic damage associated with CVD. In addition, some studies have demonstrated that KL gene is expressed in human arteries and that low vascular KL expression levels are related with clinical atherosclerotic disease. Among the epigenetic mechanisms that regulate the expression of the KL gene, methylation of the CpG islands in the promoter region is one of the most studied. In this pilot study, we propose that this mechanism participates in the regulation of vascular KL expression and contributes to the deficiency in vascular KL levels observed in CVD. Moreover, we determined the influence of different inflammatory components in the methylation status of KL promoter.
Method
We developed a case-control study that included 25 patients with diagnosis of clinical atherosclerotic vascular disease undergoing elective vascular surgery and 15 cadaveric organ donors with no medical history of CVD, respectively. Vascular fragments were retrieved from all subjects, and the degree of methylation of the KL gene promoter was assessed by bisulfite sequencing. Additionally, vascular gene expression in both groups was assessed by qPCR for KL, two DNA methyltransferases (DNMT1 and DNMT3A), and three inflammatory-related loci (TNF, IL10 and NFKB1). Serum concentrations of TNFα and IL10 were measured by ELISA immunoassay, and complementary inflammatory parameters (CRP and neutrophil/lymphocyte ratio) by standardized routine methods.
Results
The vascular tissue of patients in the case group presented a higher percent level of methylated positions in the KL promoter region (71.4±8.3% vs. 39.4±12.3%, P<0.05), as well as a significant decrease in the expression of KL gene (a 40% reduction as compared to controls, P<0.05). Considering the whole study population, the methylation degree was inversely related to the endogenous transcript levels of KL gene (r=-0.66, P<0.0001). Moreover, the expression of DNMT1 was significantly increased in the case group (P<0.05), as well as those of the proinflammatory genes TNF and NFKB1 (P<0.0001 and P<0.05, respectively), being all of them directly associated with the vascular methylation levels of KL gene (r=0.51, P<0.0001 for DNMT1; r=0.45, P<0.001 for TNF; r= 0.37, P<0.05 for NFKB1). Furthermore, vascular expression of DNMT1 and DNMT3A directly correlated with both inflammatory markers in this tissue (P<0.0001, for all). Systemic levels of IL10 presented a direct association with vascular KL gene expression (r=0.28, P<0.05), while inverse associations were observed with the methylation degree of KL gene (r=-0.38, P<0.05) and DNMT1 expression (r=-0,29, P<0.05).
Conclusion
These results suggest that the methylation of KL gene promoter in the vasculature is a mechanism associated with the inflammatory response that would partly explain its reduction during atherosclerotic injury.
Abstract
Background and Aims
Mineral metabolism imbalances and inflammation are related to the development of vascular calcification (VC). Fibroblast growth factor-23 (FGF23) is the main regulator of ...phosphate homeostasis and various studies have shown the existence of an association between elevated levels of FGF23 and the appearance of cardiovascular disease (CVD). We conducted a case-control study to test the hypothesis that serum and vascular levels of FGF23 are associated with the presence of VC. In addition, we determined the influence of inflammation in these levels.
Method
One hundred and thirty-three patients diagnosed with clinical atherosclerotic disease undergoing elective vascular surgery, and 20 cadaveric organ donors with no medical history of CVD, were included in this study. Serum levels of intact FGF23 (iFGF23), together with tumor necrosis factor-alpha (TNFα), interleukin (IL)10, were determined by ELISA. Vascular fragments of aorta, carotid and femoral arteries were obtained for assaying the gene expression of FGF23, TNF, IL10 and RUNX2 by qPCR. Immunohistochemical procedures were employed to determine vascular protein levels of FGF23, TNFα and IL10. VC was diagnosed by imaging techniques and confirmed by histological procedures including von Kossa staining.
Results
Case group presented a higher prevalence of hypertension, hypercholesterolemia and reduced estimated glomerular filtration rate, with no differences regarding other parameters. Serum iFGF23 and TNFα/IL10 ratio were higher in the case group (P<0.01 and P<0.001, respectively). Vascular expression of FGF23 was detected in 58.6% of CVD patients vs 35% of donors, with mean expression levels significantly higher in the first group (P<0.01). Vascular expression of TNF/IL10 was also increased (P<0.001) in CVD patients. FGF23 immunoreactivity was detected in 84% of CVD patients and only in 35% of controls. Immunoreactivity for FGF23 and TNFα/IL10 ratio were significantly higher in CVD patients (P<0.001 and P<0.0001, respectively).
Stratified analysis according to serum iFGF23 levels showed a higher prevalence of VC in the upper tertiles. Patients with VC presented increased levels of all the FGF23 variables including serum 1.5 (1.2-1.6) vs. 1.4 (0.9-1.5) pg/mL, P<0.01, vascular mRNA 26.1 (14.3-67.4) vs. 18.8 (8.8-312.9) log AU, P<0.01 and vascular immunoreactivity 4.6 (3.8-4.9) vs. 3.7 (3.1-4.1) log µm2, P<0.05. Moreover, FGF23 immunoreactivity was detected in 92.3% of fragments with VC and only in 53.6% of those without VC. Serum TNFα/IL10 and RUNX2 mRNA levels were also higher in this group (P<0.01 for both).
Correlation analysis showed associations of serum iFGF23 with serum TNFα (r=0.375, P<0.001), neutrophil/lymphocyte (r=0.142, P<0.05), vascular RUNX2 mRNA (r=0.55, P<0.05), and vascular FGF23 immunoreactivity (r=0.281, P<0.05) in the CVD group. Vascular FGF23 expression correlated with RUNX2 mRNA (r=0.315, P<0.05) and FGF23 immunoreactivity (r=0.254, P<0.05). Multiple regression analysis showed that iFGF23 levels were determined by UAE, HDL, FGe, calcium and TNFα levels (adjusted R2= 0.473, P<0.0001) and that vascular FGF23 mRNA expression was determined by TNFα, PCR, glucose and age (adjusted R2= 0.795, P<0.0001). Multivariate logistic regression, with VC as dependent variable, showed that both iFGF23 and vascular mRNA constitute independent risk factors for the existence of VC OR (95% CI): 1.05 and 1.12, P<0.05 for both.
Conclusion
Patients with atherosclerosis and VC present significantly higher serum concentrations of FGF23, as well as higher immunoreactivity and gene expression levels in the vascular wall compared to patients without VC. Moreover, both serum and vascular mRNA levels of FGF23 are associated with the inflammatory status. Whether the increase in systemic and vascular FGF23 can directly promote or favor the calcifying process in the vascular bed is currently an issue under discussion.
A subgroup
H
of a group
G
is called ascendant-by-finite in
G
if there exists a subgroup
K
of
H
such that
K
is ascendant in
G
and the index of
K
in
H
is finite. It is proved that a locally finite ...group with every subgroup ascendant-by-finite is locally nilpotent-by-finite. As a consequence, it is shown that the Gruenberg radical has finite index in the whole group.
Background
infection (CDI) is a major cause of diarrhea in hospitalized adult patients. This study aims to evaluate the clinical characteristics, clinical cure, recurrence and mortality in patients ...with CDI treated with either fidaxomicin or vancomycin. Methods A retrospective case-control study was conducted on patients with CDI treated with either fidaxomicin or vancomycin at a hospital from January 2019 to March 2022. Results We assessed 140 patients with CDI episodes, 70 patients treated with fidaxomicin and 70 with vancomycin. Seventy (50%) were male. Median age was 70 years old (IQR: 56-81). Fidaxomicin group had more recurrent CDI episodes within six months (59% vs 11%, p ≤ 0.001), more severity (43% vs 16%, p ≤ 0.001) and less treatment response (84% vs 100%, p ≤ 0.002) compared with vancomycin group. Recurrence and mortality rates in the follow-up period did not differ in both groups. Conclusions Our study found fidaxomicin treatment had worse outcomes due to restricted usage, potentially impacting its effectiveness in CDI. This finding is especially significant for patients with severe or recurrent CDI, as prescribing of the drug was limited until May 2022 in Spain with the lifting of this restriction, further research is necessary to better understand the potential benefits of fidaxomicin in treating CDI.
El objetivo de este trabajo es realizar un análisis estadístico y una validación de los resultados obtenidos de las simulaciones de un panel solar, con la herramienta Matlab/Simulink. Se realizaron ...una serie de mediciones de la potencia generada por el panel solar, bajo diferentes condiciones de radiación y temperatura de operación; luego se simuló el comportamiento del panel mediante el modelo matemático y el modelo del mismo establecido por Simulink; por último, se realizó un análisis de la aproximación de cada una de las simulaciones con los datos reales. Los resultados indican que, para la simulación por medio del modelo matemático del panel solar, se obtuvo un coeficiente de determinación de 0.9889, mientras que, para el modelo del panel solar establecido por Simulink fue de 0,8673. Lo anterior evidencia la buena correlación de cada una de las simulaciones realizadas con los valores reales, llegando a la conclusión que, aunque los dos métodos utilizados se acercan a la realidad, el modelo matemático del panel solar consigue una mejor aproximación.
TOMA DE DECISIONES AL FINAL DE LA VIDA Nicolás Jiménez, Pilar; Romeo Malanda, Sergio; Urruela Mora, Asier
Revista da Faculdade Mineira de Direito,
12/2020, Letnik:
23, Številka:
46
Journal Article
Recenzirano
El presente trabajo pretende abordar, desde una perspectiva eminentemente jurídica, una serie de iniciativas legislativas presentadas en el Congreso de los Diputados durante la presente legislatura ...orientadas a la regulación de la toma de decisiones al final de la vida. Con dicho fin, partiendo de la realidad legislativa actualmente vigente en España se procede a analizar, por un lado, sendas Proposiciones de Ley de derechos y garantías de la dignidad de la persona ante el proceso final de su vida (Grupo Parlamentario Popular y Grupo Parlamentario Ciudadanos) así como, por otro lado, la Proposición de Ley Orgánica de Regulación de la eutanasia (Grupo Parlamentario Socialista) que, a la vista de las mayorías parlamentarias concurrentes, está llamada a constituir la norma que regule dicha materia en el futuro próximo en España.
Posttranscriptional modifications of histones constitute an epigenetic mechanism that is closely linked to both gene silencing and activation events. Trimethylation of Histone3 at lysine 27 ...(H3K27me3) is a repressive mark that associates with developmental gene regulation during differentiation programs. In the developing pancreas, expression of the transcription factor Neurogenin3 in multipotent progenitors initiates endocrine differentiation that culminates in the generation of all pancreatic islet cell lineages, including insulin-producing beta cells. Previously, we showed that Neurogenin3 promoted the removal of H3K27me3 marks at target gene promoters in vitro, suggesting a functional connection between this factor and regulators of this chromatin mark. In the present study, we aimed to specifically evaluate whether targeting the activity of these histone modifiers can be used to modulate pancreatic endocrine differentiation. Our data show that chemical inhibition of the H3K27me3 demethylases Jmjd3/Utx blunts Neurogenin3-dependent gene activation in vitro. Conversely, inhibition of the H3K27me3 methyltransferase Ezh2 enhances both the transactivation ability of Neurogenin3 in cultured cells and the formation of insulin-producing cells during directed differentiation from pluripotent cells. These results can help improve current protocols aimed at generating insulin-producing cells for beta cell replacement therapy in diabetes.
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•Chemical inhibition of the demethylases Jmjd3/Utx impairs Neurogenin3-induced gene transactivation.•Chemical inhibition of the methyltransferase Ezh2 enhances Neurogenin 3-induced gene transactivation.•Inhibition of Ezh2 can be used to improve Neurogenin3-dependent cell transdifferentiation towards the endocrine lineage.•Ezh2 activity during formation of Neurogenin3+ cells improves derivation of insulin-producing cells from human iPSC.
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