729 research outputs found

    Genomic characterization of individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced lung cancer

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    Single nucleotide polymorphisms (SNPs) may modulate individual susceptibility to carcinogens. We designed a genome-wide association study to characterize individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced non-small cell lung cancer (NSCLC), and we validated our results. We hypothesized that this strategy would enrich the frequencies of the alleles that contribute to the observed traits. We genotyped 2.37 million SNPs in 95 extreme phenotype individuals, that is: heavy smokers that either developed NSCLC at an early age (extreme cases); or did not present NSCLC at an advanced age (extreme controls), selected from a discovery set (n=3631). We validated significant SNPs in 133 additional subjects with extreme phenotypes selected from databases including >39,000 individuals. Two SNPs were validated: rs12660420 (p(combined)=5.66x10(-5); ORcombined=2.80), mapping to a noncoding transcript exon of PDE10A; and rs6835978 (p(combined)=1.02x10(-4); ORcombined=2.57), an intronic variant in ATP10D. We assessed the relevance of both proteins in early-stage NSCLC. PDE10A and ATP10D mRNA expressions correlated with survival in 821 stage I-II NSCLC patients (p=0.01 and p<0.0001). PDE10A protein expression correlated with survival in 149 patients with stage I-II NSCLC (p=0.002). In conclusion, we validated two variants associated with extreme phenotypes of high and low risk of developing tobacco-induced NSCLC. Our findings may allow to identify individuals presenting high and low risk to develop tobacco-induced NSCLC and to characterize molecular mechanisms of carcinogenesis and resistance to develop NSCLC

    Morbid liver manifestations are intrinsically bound to metabolic syndrome and nutrient intake based on a machine-learning cluster analysis

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    Metabolic syndrome (MetS) is one of the most important medical problems around the world. Identification of patient ' s singular characteristic could help to reduce the clinical impact and facilitate individualized management. This study aimed to categorize MetS patients using phenotypical and clinical variables habitually collected during health check-ups of individuals considered to have high cardiovascular risk. The selected markers to categorize MetS participants included anthropometric variables as well as clinical data, biochemical parameters and prescribed pharmacological treatment. An exploratory factor analysis was carried out with a subsequent hierarchical cluster analysis using the z-scores from factor analysis. The first step identified three different factors. The first was determined by hypercholesterolemia and associated treatments, the second factor exhibited glycemic disorders and accompanying treatments and the third factor was characterized by hepatic enzymes. Subsequently four clusters of patients were identified, where cluster 1 was characterized by glucose disorders and treatments, cluster 2 presented mild MetS, cluster 3 presented exacerbated levels of hepatic enzymes and cluster 4 highlighted cholesterol and its associated treatments Interestingly, the liver status related cluster was characterized by higher protein consumption and cluster 4 with low polyunsaturated fatty acid intake. This research emphasized the potential clinical relevance of hepatic impairments in addition to MetS traditional characterization for precision and personalized management of MetS patients

    La enseñanza del metabolismo: retos y oportunidades

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    En el marco del Proyecto de InnovaciĂłn Educativa de la Universidad de MĂĄlaga PIE15-163, cuya descripciĂłn y resultados incluimos, decidimos que esta era una excelente oportunidad para reflexionar acerca de la enseñanza del metabolismo y de poner por escrito dichas reflexiones en un libro. Quisimos y pudimos contar con la colaboraciĂłn de buena parte de los compañeros del Departamento de BiologĂ­a Molecular y BioquĂ­mica que apoyaron con su firma el proyecto PIE15-163 y extendimos nuestra invitaciones a otros compañeros de dentro y fuera de la Universidad de MĂĄlaga. Del Departamento de BiologĂ­a Molecular y BioquĂ­mica de la Universidad de MĂĄlaga hemos recibido aportaciones de los catedrĂĄticos Victoriano Valpuesta FernĂĄndez, Ana RodrĂ­guez Quesada y Antonio Heredia Bayona, los profesores titulares MarĂ­a Josefa PĂ©rez RodrĂ­guez, JosĂ© Luis Urdiales Ruiz e Ignacio Fajardo Paredes y la investigadora postdoctoral y profesora sustituta interina Beatriz MartĂ­nez Poveda. De otros departamentos de la Universidad de MĂĄlaga hemos contado con las aportaciones de la catedrĂĄtica del Departamento de Especialidades QuirĂșrgicas, BioquĂ­mica e InmunologĂ­a Pilar Morata Losa, del catedrĂĄtico del Departamento de Lenguajes y Ciencias de la ComputaciĂłn JosĂ© Francisco Aldana Montes y los componentes de su grupo de investigaciĂłn Khaos Ismael Navas Delgado, MarĂ­a JesĂșs GarcĂ­a Godoy, Esteban LĂłpez Camacho y Maciej Rybinski, del catedrĂĄtico Ángel Blanco LĂłpez, del Área de Conocimiento de DidĂĄctica de las Ciencias Experimentales y del Doctor en Ciencias QuĂ­micas y actual doctorando del Programa de Doctorado "EducaciĂłn y ComunicaciĂłn Social" Ángel Luis GarcĂ­a Ponce. De fuera de la Universidad de MĂĄlaga, hemos contado con las aportaciones del catedrĂĄtico de la Universidad de La Laguna NĂ©stor V. Torres Darias, de la catedrĂĄtica de la Universitat de les Illes Balears Pilar Roca Salom y de sus compañeros los profesores Jorge Sastre Serra y Jordi Oliver, de los catedrĂĄticos de la Universidad de Granada Rafael Salto GonzĂĄlez y MarĂ­a Dolores GirĂłn GonzĂĄlez y su colaborador el Dr. JosĂ© DĂĄmaso VĂ­lchez Rienda, del profesor titular de la Universidad de AlcalĂĄ Ángel HerrĂĄez, del investigador postdoctoral de la Universidad de Erlangen (Alemania) Guido Santos y del investigador postdoctoral de la empresa Brain Dynamics Carlos RodrĂ­guez Caso.Hemos estructurado los contenidos del libro en diversas secciones. La primera presenta el Proyecto en cuyo marco se ha gestado la iniciativa que ha conducido a la ediciĂłn del presente libro. La segunda secciĂłn la hemos titulado "ÂżQuĂ© metabolismo?" e incluye diversas aportaciones personales que reflexionan acerca de quĂ© metabolismo debe conocer un graduado en BioquĂ­mica, en BiologĂ­a, en QuĂ­mica, en Farmacia o en Medicina, asĂ­ como una aportaciĂłn acerca de quĂ© bioquĂ­mica estructural y enzimologĂ­a son Ăștiles y necesarias para un estudiante que vaya a afrontar el estudio del metabolismo. La tercera secciĂłn, "Bases conceptuales", analiza las aportaciones del aprendizaje colaborativo, el contrato de aprendizaje y el aprendizaje basado en la resoluciĂłn de casos prĂĄcticos a la mejora del proceso enseñanza-aprendizaje dentro del campo de la BioquĂ­mica y BiologĂ­a Molecular, mĂĄs concretamente en el estudio del metabolismo. La cuarta secciĂłn se titula "Herramientas", es la mĂĄs extensa e incluye las diversas aportaciones centradas en propuestas concretas de aplicaciĂłn relevantes y Ăștiles para la mejora de la docencia-aprendizaje del metabolismo. Sigue una secciĂłn dedicada a presentar de forma resumida los "Resultados" del proyecto PIE15-163. El libro concluye con una "coda final" en la que se reflexiona acerca del aprendizaje de la QuĂ­mica a la luz de la investigaciĂłn didĂĄctica.Patrocinado por el Proyecto de InnovaciĂłn Educativa de la Universidad de MĂĄlaga PIE15-16

    Mediterranean, DASH, and MIND Dietary Patterns and Cognitive Function: The 2-Year Longitudinal Changes in an Older Spanish Cohort

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    Background and Aims: Plant-forward dietary patterns have been associated with cardiometabolic health benefits, which, in turn, have been related to cognitive performance with inconsistent findings. The objective of this study was to examine the relationship between baseline adherence to three a priori dietary patterns (Mediterranean, DASH, and MIND diets) with 2-year changes in cognitive performance in older adults with overweight or obesity and high cardiovascular disease risk. Methods: A prospective cohort analysis was conducted within the PREDIMED-Plus trial, involving 6,647 men and women aged 55-75 years with overweight or obesity and metabolic syndrome. Using a validated, semiquantitative 143-item food frequency questionnaire completed at baseline, the dietary pattern adherence scores were calculated. An extensive neuropsychological test battery was administered at baseline and 2-year follow-up. Multivariable-adjusted linear regression models were used to assess associations between 2-year changes in cognitive function z-scores across tertiles of baseline adherence to the a priori dietary patterns. Results: Adherence to the Mediterranean diet at baseline was associated with 2-year changes in the general cognitive screening Mini-Mental State Examination (MMSE, ÎČ: 0.070; 95% CI: 0.014, 0.175, P-trend = 0.011), and two executive function-related assessments: the Trail Making Tests Part A (TMT-A, ÎČ: −0.054; 95% CI: −0.110, − 0.002, P-trend = 0.047) and Part B (TMT-B, ÎČ: −0.079; 95% CI: −0.134, −0.024, P-trend = 0.004). Adherence to the MIND diet was associated with the backward recall Digit Span Test assessment of working memory (DST-B, ÎČ: 0.058; 95% CI: 0.002, 0.114, P-trend = 0.045). However, higher adherence to the DASH dietary pattern was not associated with better cognitive function over a period of 2 years. Conclusion: In older Spanish individuals with overweight or obesity and at high cardiovascular disease risk, higher baseline adherence to the Mediterranean dietary pattern may be associated with better cognitive performance than lower adherence over a period of 2 years

    Ultra-processed foods consumption as a promoting factor of greenhouse gas emissions, water, energy, and land use: A longitudinal assessment

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    Background: Dietary patterns can produce an environmental impact. Changes in people's diet, such as the increased consumption of ultra-processed food (UPF) can not only influence human health but also environment sustainability. Objectives: Assessment of the impact of 2-year changes in UPF consumption on greenhouse gas emissions and water, energy and land use. Design A 2-year longitudinal study after a dietary intervention including 5879 participants from a Southern European population between the ages of 55-75 years with metabolic syndrome. Methods Food intake was assessed using a validated 143-item food frequency questionnaire, which allowed classifying foods according to the NOVA system. In addition, sociodemographic data, Mediterranean diet adherence, and physical activity were obtained from validated questionnaires. Greenhouse gas emissions, water, energy and land use were calculated by means of the Agribalyse¼ 3.0.1 database of environmental impact indicators for food items. Changes in UPF consumption during a 2-year period were analyzed. Statistical analyses were conducted using computed General Linear Models. Results: Participants with major reductions in their UPF consumption reduced their impact by −0.6 kg of CO2eq and −5.3 MJ of energy. Water use was the only factor that increased as the percentage of UPF was reduced. Conclusions: Low consumption of ultra-processed foods may contribute to environmental sustainability. The processing level of the consumed food should be considered not only for nutritional advice on health but also for environmental protection

    Isotemporal substitution of inactive time with physical activity and time in bed: cross-sectional associations with cardiometabolic health in the PREDIMEDPlus study

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    Background: This study explored the association between inactive time and measures of adiposity, clinical parameters, obesity, type 2 diabetes and metabolic syndrome components. It further examined the impact of reallocating inactive time to time in bed, light physical activity (LPA) or moderate-to-vigorous physical activity (MVPA) on cardio-metabolic risk factors, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults. Methods: This is a cross-sectional analysis of baseline data from 2189 Caucasian men and women (age 55-75 years, BMI 27-40 Kg/m2) from the PREDIMED-Plus study (http://www.predimedplus.com/). All participants had ≄3 components of the metabolic syndrome. Inactive time, physical activity and time in bed were objectively determined using triaxial accelerometers GENEActiv during 7 days (ActivInsights Ltd., Kimbolton, United Kingdom). Multiple adjusted linear and logistic regression models were used. Isotemporal substitution regression modelling was performed to assess the relationship of replacing the amount of time spent in one activity for another, on each outcome, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults. Results: Inactive time was associated with indicators of obesity and the metabolic syndrome. Reallocating 30 min per day of inactive time to 30 min per day of time in bed was associated with lower BMI, waist circumference and glycated hemoglobin (HbA1c) (all p-values < 0.05). Reallocating 30 min per day of inactive time with 30 min per day of LPA or MVPA was associated with lower BMI, waist circumference, total fat, visceral adipose tissue, HbA1c, glucose, triglycerides, and higher body muscle mass and HDL cholesterol (all p-values < 0.05). Conclusions: Inactive time was associated with a poor cardio-metabolic profile. Isotemporal substitution of inactive time with MVPA and LPA or time in bed could have beneficial impact on cardio-metabolic health

    Relationship between olive oil consumption and ankle-brachial pressure index in a population at high cardiovascular risk

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    The aim of this study was to ascertain the association between the consumption of different categories of edible olive oils (virgin olive oils and olive oil) and olive pomace oil and ankle-brachial pressure index (ABI) in participants in the PREDIMED-Plus study, a trial of lifestyle modification for weight and cardiovascular event reduction in individuals with overweight/obesity harboring the metabolic syndrome. Methods: We performed a cross-sectional analysis of the PREDIMED-Plus trial. Consumption of any category of olive oil and olive pomace oil was assessed through a validated food-frequency questionnaire. Multivariable linear regression models were fitted to assess associations between olive oil consumption and ABI. Additionally, ABI ≀1 was considered as the outcome in logistic models with different categories of olive oil and olive pomace oil as exposure. Results: Among 4330 participants, the highest quintile of total olive oil consumption (sum of all categories of olive oil and olive pomace oil) was associated with higher mean values of ABI (beta coefficient: 0.014, 95% confidence interval [CI]: 0.002, 0.027) (p for trend = 0.010). Logistic models comparing the consumption of different categories of olive oils, olive pomace oil and ABI ≀1 values revealed an inverse association between virgin olive oils consumption and the likelihood of a low ABI (odds ratio [OR] 0.73, 95% CI [0.56, 0.97]), while consumption of olive pomace oil was positively associated with a low ABI (OR 1.22 95% CI [1.00, 1.48]). Conclusions: In a Mediterranean population at high cardiovascular risk, total olive oil consumption was associated with a higher mean ABI. These results suggest that olive oil consumption may be beneficial for peripheral artery disease prevention, but longitudinal studies are needed

    In Vitro and In Vivo Efficacy of Ether Lipid Edelfosine against Leishmania spp. and SbV-Resistant Parasites

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    Leishmaniasis represents a major international health problem, has a high morbidity and mortality rate, and is classified as an emerging and uncontrolled disease by the World Health Organization. The migration of population from endemic to nonendemic areas, and tourist activities in endemic regions are spreading the disease to new areas. Unfortunately, treatment of leishmaniasis is far from satisfactory, with only a few drugs available that show significant side-effects. Here, we show in vitro and in vivo evidence for the antileishmanial activity of the ether phospholipid edelfosine, being effective against a wide number of Leishmania spp. causing cutaneous, mucocutaneous and visceral leishmaniasis. Our experimental mouse and hamster models demonstrated not only a significant antileishmanial activity of edelfosine oral administration against different wild-type Leishmania spp., but also against parasites resistant to pentavalent antimonials, which constitute the first line of treatment worldwide. In addition, edelfosine exerted a higher antileishmanial activity and a lower proneness to generate drug resistance than miltefosine, the first drug against leishmaniasis that can be administered orally. These data, together with our previous findings, showing an anti-inflammatory action and a very low toxicity profile, suggest that edelfosine is a promising orally administered drug for leishmaniasis, thus warranting clinical evaluation
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