Oxidación e inflamación en la hiperlipidemia familiar combinada.

RESUMEN La hiperlipidemia familiar combinada (HFC) es una enfermedad muy frecuente, con una prevalencia estimada del 1-3% en la población general y hasta del 20% en pacientes con cardiopatía isquémica precoz. Su base metabólica y genética no ha sido todavía identificada, siendo el mecanismo más probable la interacción de diferentes genes y el ambiente. Se caracteriza por presentar varios fenotipos lipoproteicos en la misma familia, e incluso en el mismo individuo, a lo largo de su evolución, generalmente por cambios en los factores exógenos. El diagnóstico se basa en el estudio familiar y la expresión fenotípica variable con elevación de la apo B plasmática. Los mecanismos patogénicos implicados en la HFC son muy heterogéneos y no totalmente conocidos. Se consideran fundamentalmente los siguientes: hiperproducción hepática de VLDL, defecto en la actividad de la lipoprotein lipasa, alteraciones en la esterificación de los ácidos grasos en el tejido adiposo y la presencia de resistencia a la insulina (RI). Sin embargo, el daño orgánico y el inicio y desarrollo de la enfermedad cardiovascular es heterogéneo en este grupo de pacientes, lo que indica que necesariamente deben existir otros factores de riesgo, además de la dislipemia, que justifiquen esta variabilidad. En este sentido, dos factores poco estudiados y emergentes son el nivel de estrés oxidativo (EO) y la inflamación. La HFC es un modelo genético de hiperlipidemia mixta con RI, alteración de la lipemia postprandial y aterosclerosis precoz. En este sentido, la hipótesis de trabajo es: en la HFC debe existir estrés oxidativo y activación de factores inflamatorios implicados en el inicio y desarrollo de la AE que estarán relacionados con el grado de RI y sus determinantes clínicos. Para evaluar dicha hipótesis, se plantearon dos objetivos fundamentales: 1. Conocer el nivel de EO y factores de inflamación relacionados con la AE en sujetos con HFC y controles. 2. Analizar la relación entre parámetros antropométricos y grado de RI con el EO y la inflamación en sujetos con HFC y controles. Se estudiaron 42 sujetos con HFC en prevención primaria, no diabéticos, no fumadores, no hipertensos y sin tratamiento (dado que todas estas situaciones son capaces de generar EO e inflamación) seleccionados de forma consecutiva, y 24 controles. En todos ellos se determinaron parámetros clínicos y antropométricos (presión arterial, edad, peso, talla e IMC), parámetros bioquímicos (perfil lipídico e hidrocarbonado), parámetros de estrés oxidativo (8-oxo-dG, MDA, GSSG y GSSG/GSH, como marcadores de oxidación sistémica; SOD, catalasa y GPX, como sistemas antioxidantes; y GSH, como marcador de reducción) y parámetros de inflamación (NF-κβ, adiponectina, IL-1, IL-6 y PCRas). Tras analizar los resultados observamos que: - La HFC es un modelo genético de dislipemia mixta con RI. - En los sujetos con HFC existe elevación de los productos de oxidación y descenso de los sistemas antioxidantes. - En los sujetos con HFC existe elevación de la inflamación sistémica. - NF-κβ, como factor clave en la regulación de los procesos de inflamación y oxidación, está elevado en sujetos con HFC. - Las variables antropométricas (tipo y grado de obesidad) no tienen efecto significativo en la inflamación y oxidación en sujetos con HFC, ni en el grupo completo. - La RI se relaciona de forma independiente con parámetros de inflamación y oxidación en sujetos con HFC. - La inflamación es el factor predictor independiente de la RI en sujetos con HFC y no el tipo y grado de obesidad ni la dislipemia. __________________________________________________________________________________________________Familial combined hyperlipidemia (FCH) is a frequent disease with a prevalence of 1-3% in general population, characterized by different familial lipoproteic phenotypes, usually related with changes in exogen factors. Diagnosis is based in familial evaluation and elevated plasmatic apo B. Main pathogenic pathways, although not completely known, are: VLDL overproduction in liver, decreased lipoprotein lipase activity, defect in adipose tissue metabolism and insulin resistance (IR). Nevertheless organic damage, the beginning and appearance of cardiovascular disease is heterogeneous in these patients so other risk factors (not only dyslipidaemia) should exist to explain this variability. Two emergent and non studied factors are oxidative stress (OE) and inflammation. FCH is a genetic model of mixed hyperlipidaemia with insulin resistance, defect in postprandial lipaemia and early atherosclerosis. The hypothesis proposed is: in FCH should exist OE and activation of inflammatory markers implicated in the beginning and progression of atherosclerosis and them should be related to IR degree. Forty-two FCH, non diabetic, non smoker, non hypertensive and non treated subjects in primary prevention consecutively selected and twenty-four controls were studied. Clinical and anthropometric parameters (blood pressure, age, weight, height and body mass index), biochemical parameters (lipid and glucose profile), OE parameters (8-oxo-dG, MDA, GSSG and GSSG/GSH as markers of systemic oxidation; SOD, catalase and GPX as antioxidant systems; and GSH as reduction marker) and markers of inflammation (NF-κβ, adiponectine, IL-1, IL-6 and hsCRP) were determined. The analysis of results showed: - FCH is a genetic model of mixed dyslipidaemia with IR. - In FCH subjects oxidative markers are elevated and antioxidant systems are decreased. - Systemic inflammation is elevated in FCH subjects. - NF-κβ as clue regulator of inflammatory and oxidative process is elevated in FCH subjects. - Anthropometric parameters (type and degree of obesity) do not influence oxidation and inflammation in FCH subjects neither control subjects. - IR is independently related to inflammation and oxidation parameters in FCH subjects. - Inflammatory state is a independent predictor factor of IR in FCH subjects without relation to type and degree of obesity and dyslipidaemia

Evaluación de la influencia de los recursos computacionales en la QoE del servicio.

The new generation of mobile networks goes beyond radio communications by providing a resilient and flexible architecture. In this context, the virtualization of Radio Access Networks (vRAN) completes the Network Func4on Virtualization (NFV) milestone, enabling a distributed and scalable network architecture. However, this approach increases the complexity of management tasks as computing resources start to play an essential role in the network provisioning process. In this sense, this work aims to assess the impact of computational resources on the delivery of video streaming services. The results obtained prove that inadequate resource assignment to vRAN instances leads to degradation of the Quality of Experience (QoE), even if the allocation of radio resources is adequate for the service.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Assessment of the impact of limited computing resources on vRAN deployment.

The new generation of mobile networks goes beyond radio communications by providing a resilient and flexible architecture. In this context, the virtualization of Radio Access Networks (vRAN) completes the Network Function Virtualization (NFV) milestone, enabling a distributed and scalable network architecture. However, this approach increases the complexity of management tasks where computing resources start to play an essential role in the network provisioning process. In this sense, this work aims to assess the impact of computational resources on network performance. The results obtained prove that inadequate resource assignment to vRAN instances leads to service degradation that may remain unnoticed by the network operator. Furthermore, the importance of the vRAN configuration in these scenarios is highlighted, as allocated compute resources can have unintended effects on the quality of service (QoS).Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Lipoprotein hydrophobic core lipids are partially extruded to surface in smaller HDL : "Herniated" HDL, a common feature in diabetes

Recent studies have shown that pharmacological increases in HDL cholesterol concentrations do not necessarily translate into clinical benefits for patients, raising concerns about its predictive value for cardiovascular events. Here we hypothesize that the size-modulated lipid distribution within HDL particles is compromised in metabolic disorders that have abnormal HDL particle sizes, such as type 2 diabetes mellitus (DM2). By using NMR spectroscopy combined with a biochemical volumetric model we determined the size and spatial lipid distribution of HDL subclasses in a cohort of 26 controls and 29 DM2 patients before and after two drug treatments, one with niacin plus laropiprant and another with fenofibrate as an add-on to simvastatin. We further characterized the HDL surface properties using atomic force microscopy and fluorescent probes to show an abnormal lipid distribution within smaller HDL particles, a subclass particularly enriched in the DM2 patients. The reduction in the size, force cholesterol esters and triglycerides to emerge from the HDL core to the surface, making the outer surface of HDL more hydrophobic. Interestingly, pharmacological interventions had no effect on this undesired configuration, which may explain the lack of clinical benefits in DM2 subjects

Type 1 diabetic mellitus patientswith increased atherosclerosisriskdisplay decreased CDKN2A/2B/2BAS gene expression in leukocytes

Background: Type 1 diabetes mellitus (T1DM) patients display increased risk of cardiovascular disease (CVD) and are characterized by a diminished regulatory T (Treg) cell content or function. Previous studies have shown an association between decreased CDKN2A/2B/2BAS gene expression and enhanced CVD. In the present study the potential relationship between CDKN2A/2B/2BAS gene expression, immune cell dysfunction and increased cardiovascular risk in T1DM patients was explored. Methods: A cross-sectional study was performed in 90 subjects divided into controls and T1DM patients. Circulating leukocyte subpopulations analysis by flow cytometry, expression studies on peripheral blood mononuclear cell by qPCR and western blot and correlation studies were performed in both groups of subjects. Results: Analysis indicated that, consistent with the described T cell dysfunction, T1DM subjects showed decreased circulating CD4+CD25+CD127- Treg cells. In addition, T1DM subjects had lower mRNA levels of the transcription factors FOXP3 and RORC and lower levels of IL2 and IL6 which are involved in Treg and Th17 cell differentiation, respectively. T1DM patients also exhibited decreased mRNA levels of CDKN2A (variant 1 p16Ink4a), CDKN2A (p14Arf, variant 4), CDKN2B (p15Ink4b) and CDKN2BAS compared with controls. Notably, T1DM patients had augmented pro-atherogenic CD14++CD16+-monocytes, which predict cardiovascular acute events and enhanced common carotid intima-media thickness (CC-IMT). Conclusions: Decreased expression of CDKN2A/2B/2BAS in leukocytes associates with increased CC-IMT atherosclerosis surrogate marker and proatherogenic CD14++CD16+ monocytes in T1DM patients. These results suggest a potential role of CDKN2A/2B/2BAS genes in CVD risk in T1DM

Impacto de la asignación de recursos CPU sobre el rendimiento de la vRAN en O-Cloud.

The need for mobile operators to have an infrastructure that can handle everincreasing traffic and support the development of more demanding services at lower costs has led to the emergence of the O-RAN paradigm. This organiza.on proposes an unbundled and virtualized Radio Access Network (vRAN) running on commodity servers, moving away from tradi.onal monolithic network environments. In this context, managing the available compu.ng resources at the host machine is key for mee.ng network requirements without was.ng resources. In this regard, this work abempts to evaluate the impact of computa.onal and radio resources on network performance under different radio configura.ons. The results prove that misalloca.ng resources to vRAN instances can lead to network performance degrada.on and that addi.onal dedicated resources do not always translate into beber performance.Trabajo financiado por el Ministerio de Asuntos Económicos y Transformación Digital y la Unión Europea a través de fondos NextGenerationEU, en el marco del Plan de Recuperación, Transformación y Resiliencia y el Mecanismo de Recuperación y Resiliencia bajo el proyecto MAORI. Además, ha sido apoyado por el Ministerio de Ciencia e Innovación a través de las becas FPU19/04468 y FPU21/04472. También ha sido parcialmente financiado a través del II Plan Propio de Investigación y Transferencia de la Universidad de Málaga (Campus de Excelencia Internacional Andalucía Tech). - Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Novel Immune Features of the Systemic Inflammation Associated with Primary Hypercholesterolemia: Changes in Cytokine/Chemokine Profile, Increased Platelet and Leukocyte Activation

Primary hypercholesterolemia (PH) is associated with a low grade systemic inflammation that is likely the main driver of premature atherosclerosis. Accordingly, we characterized the immune cell behaviour in PH and its potential consequences. Whole blood from 22 PH patients and 21 age-matched controls was analysed by flow cytometry to determine the percentage of leukocyte immunophenotypes, activation, and platelet-leukocyte aggregates. Plasma markers were determined by Enzyme-Linked ImmunoSorbent Assay (ELISA). The adhesion of platelet-leukocyte aggregates to tumor necrosis factor-α (TNFα)-stimulated arterial endothelium was investigated using the dynamic model of the parallel-plate flow chamber. PH patients presented greater percentage of Mon 3 monocytes, Th2 and Th17 lymphocytes, activated platelets, and leukocytes than controls. The higher percentages of circulating platelet-neutrophil, monocyte and lymphocyte aggregates in patients caused increased platelet-leukocyte adhesion to dysfunctional arterial endothelium. Circulating CXCL8, CCL2, CX3CL1, and IL-6 levels positively correlated with key lipid features of PH, whereas negative correlations were found for IL-4 and IL-10. We provide the first evidence that increased platelet and leukocyte activation leads to elevated platelet-leukocyte aggregates in PH and augmented arterial leukocyte adhesiveness, a key event in atherogenesis. Accordingly, modulation of immune system behavior might be a powerful target in the control of further cardiovascular disease in PH

Epidemiological trends of HIV/HCV coinfection in Spain, 2015-2019

Altres ajuts: Spanish AIDS Research Network; European Funding for Regional Development (FEDER).Objectives: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. Methods: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. Results: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). Conclusions: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population

Tema 12_Cas clínic_Avaluació de l'estat nutricional

El document forma part dels materials docents programats mitjançant l'ajut del Servei de Política Lingüística de la Universitat de València.Es tracta de material docent de l’assignatura endocrinologia i nutrició II del Grau de Medicina. S’inclou el cas clínic comentat corresponent al tema 12 de l’assignatura. Es tracta d’una pacient amb ingressada a l’hospital amb sospita de malnutrició. Es desenvolupa el cribratge de malnutrició, així com l'etiologia, el diagnòstic, el diagnòstic diferencial i el tractament.This is teaching material for the endocrinology and nutrition II subject of the Degree in Medicine. The commented clinical case corresponding to topic 12 of the subject is included. This is a patient admitted to the hospital with suspected malnutrition. Malnutrition screening is developed, as well as etiology, diagnosis, differential diagnosis, and treatment