Characteristics of participants who benefit most from personalised nutrition: findings from the pan-European Food4Me randomised controlled trial.

Little is known about who would benefit from Internet-based personalised nutrition (PN) interventions. This study aimed to evaluate the characteristics of participants who achieved greatest improvements (i.e. benefit) in diet, adiposity and biomarkers following an Internet-based PN intervention. Adults (n 1607) from seven European countries were recruited into a 6-month, randomised controlled trial (Food4Me) and randomised to receive conventional dietary advice (control) or PN advice. Information on dietary intake, adiposity, physical activity (PA), blood biomarkers and participant characteristics was collected at baseline and month 6. Benefit from the intervention was defined as ≥5 % change in the primary outcome (Healthy Eating Index) and secondary outcomes (waist circumference and BMI, PA, sedentary time and plasma concentrations of cholesterol, carotenoids and omega-3 index) at month 6. For our primary outcome, benefit from the intervention was greater in older participants, women and participants with lower HEI scores at baseline. Benefit was greater for individuals reporting greater self-efficacy for 'sticking to healthful foods' and who 'felt weird if [they] didn't eat healthily'. Participants benefited more if they reported wanting to improve their health and well-being. The characteristics of individuals benefiting did not differ by other demographic, health-related, anthropometric or genotypic characteristics. Findings were similar for secondary outcomes. These findings have implications for the design of more effective future PN intervention studies and for tailored nutritional advice in public health and clinical settings.

Fatty acids, epigenetic mechanisms and chronic diseases: a systematic review.

BACKGROUND: Chronic illnesses like obesity, type 2 diabetes (T2D) and cardiovascular diseases, are worldwide major causes of morbidity and mortality. These pathological conditions involve interactions between environmental, genetic, and epigenetic factors. Recent advances in nutriepigenomics are contributing to clarify the role of some nutritional factors, including dietary fatty acids in gene expression regulation. This systematic review assesses currently available information concerning the role of the different fatty acids on epigenetic mechanisms that affect the development of chronic diseases or induce protective effects on metabolic alterations. METHODS: A targeted search was conducted in the PubMed/Medline databases using the keywords "fatty acids and epigenetic". The data were analyzed according to the PRISMA-P guidelines. RESULTS: Consumption fatty acids like n-3 PUFA: EPA and DHA, and MUFA: oleic and palmitoleic acid was associated with an improvement of metabolic alterations. On the other hand, fatty acids that have been associated with the presence or development of obesity, T2D, pro-inflammatory profile, atherosclerosis and IR were n-6 PUFA, saturated fatty acids (stearic and palmitic), and trans fatty acids (elaidic), have been also linked with epigenetic changes. CONCLUSIONS: Fatty acids can regulate gene expression by modifying epigenetic mechanisms and consequently result in positive or negative impacts on metabolic outcomes.

Impact of dietary lipoic acid supplementation on liver mitochondrial bioenergetics and oxidative status on normally fed Wistar rats.

The aim of this study was to examine the effects of α-lipoic acid (α-LA) on liver mitochondrial bioenergetics and oxidative status for 8 weeks in normal-healthy animals. A pair-fed group was included to differentiate between α-LA direct effects and those changes due to reduced food intake. α-LA decreased body weight gain, liver weight and insulin levels with no differences compared to its pair-fed group. α-LA significantly reduced energy efficiency, the activity of the electron transport chain complexes and induced a lower efficiency of oxidative phosphorylation with reduced ATP production. α-LA supplementation directly decreased plasma triglycerides (TGs), free fatty acids and ketone bodies levels. A significant reduction in hepatic TG content was also observed. A significant up-regulation of Cpt1a, Acadl and Sirt3, all ß-oxidation genes, along with a significant deacetylation of the forkhead transcription factor 3a (FOXO3A) was found in α-LA-treated animals. Thus, α-LA along with a standard chow diet has direct actions on lipid metabolism and liver by modulating mitochondrial function in normal-weight rats. These results should be taken into account when α-LA is administered or recommended to a healthy population.

Clinical experience with ceftolozane/tazobactam in patients with serious infections due to resistant Pseudomonas aeruginosa.

OBJECTIVES: The incidence of infections caused by multidrug-resistant Pseudomonas aeruginosa (MDR-Pa) has become a concern of increasing relevance nowadays. Ceftolozane/tazobactam (C/T) is a novel fifth-generation cephalosporin/ß-lactamase inhibitor combination with activity against MDR-Pa. METHODS: The clinical records of all patients diagnosed from May 2016 to May 2017 with an infection due to a MDR-Pa treated with C/T were retrospectively reviewed. RESULTS: A total of 23 patients with 24 episodes of infection due to MDR-Pa were included. The minimum inhibitory concentration (MIC) of C/T against MDR-Pa ranged from 0.75-8µg/mL. In 14 cases (58%) the use of C/T was off-label, including 8 respiratory tract infections (RTIs) and 6 skin and soft-tissue infections, whilst in 10 cases the use was for approved indications, including 7 urinary tract infections and 3 intra-abdominal infections. C/T was the first-line therapy in only three cases with a mean±standard deviation treatment duration of 9.3±4 days, and it was associated with another active drug (aminoglycoside or colistin) in 16 cases. The global clinical cure rate was 88% (21/24 episodes), and the 6-week mortality rate was 22% (5/23 patients) being higher in RTIs (37%). In these infections, three patients received 2/1g every 8h (q8h) and were cured without mortality, whilst three (60%) of five patients receiving 1/0.5g q8h died. CONCLUSION: C/T had good clinical responses in different types of infection, including both FDA-accepted and off-label indications. The results support the use of higher doses in RTIs.

[Methodological aspects of integrated care pathways]. / Aspectos metodológicos de los procesos asistenciales integrados (PAI).

An Integrated Healthcare Pathway (PAI) is a tool which has as its aim to increase the effectiveness of clinical performance through greater coordination and to ensure continuity of care. PAI places the patient as the central focus of the organisation of health services. It is defined as the set of activities carried out by the health care providers in order to increase the level of health and satisfaction of the population receiving services. The development of a PAI requires the analysis of the flow of activities, the inter-relationships between professionals and care teams, and patient expectations. The methodology for the development of a PAI is presented and discussed in this article, as well as the success factors for its definition and its effective implementation. It also explains, as an example, the recent PAI for Hypoglycaemia in patients with Type 2 Diabetes Mellitus developed by a multidisciplinary team and supported by several scientific societies.

Comparison of the portion size and frequency of consumption of 156 foods across seven European countries: insights from the Food4ME study.

There are no standardised serving/portion sizes defined for foods consumed in the European Union (EU). Typical serving sizes can deviate significantly from the 100 g/100 ml labelling specification required by the EU legislation. Where the nutritional value of a portion is specified, the portion size is determined by the manufacturers. Our objective was to investigate the potential for standardising portion sizes for specific foods, thereby ensuring complementarity across countries. We compared portion size for 156 food items measured using a food frequency questionnaire across the seven countries participating in the Food4me study. The probability of consuming a food and the frequency of consumption differed across countries for 93% and 58% of the foods, respectively. However, the individual country mean portion size differed from the average across countries in only 16% of comparisons. Thus, although dietary choices vary markedly across countries, there is much less variation in portion sizes. Our results highlight the potential for standardisation of portion sizes on nutrition labels in the EU.

Peripheral neuron plasticity is enhanced by brief electrical stimulation and overrides attenuated regrowth in experimental diabetes.

Peripheral nerve regrowth is less robust than commonly assumed, particularly when it accompanies common clinical scenarios such as diabetes mellitus. Brief extracellular electrical stimulation (ES) facilitates the regeneration of peripheral nerves in part through early activation of the conditioning injury response and BDNF. Here, we explored intrinsic neuronal responses to ES to identify whether ES might impact experimental diabetes, where regeneration is attenuated. ES altered several regeneration related molecules including rises in tubulin, Shh (Sonic hedgehog) and GAP43 mRNAs. ES was associated with rises in neuronal intracellular calcium but its strict linkage to regrowth was not confirmed. In contrast, we identified PI3K-PTEN involvement, an association previously linked to diabetic regenerative impairment. Following ES there were declines in PTEN protein and mRNA both in vitro and in vivo and a PI3K inhibitor blocked its action. In vitro, isolated diabetic neurons were capable of mounting robust responsiveness to ES. In vivo, ES improved electrophysiological and behavioral indices of nerve regrowth in a chronic diabetic model of mice with pre-existing neuropathy. Regrowth of myelinated axons and reinnervation of the epidermis were greater following ES than sham stimulation. Taken together, these findings identify a role for ES in supporting regeneration during the challenges of diabetes mellitus.

Reshaping faecal gut microbiota composition by the intake of trans-resveratrol and quercetin in high-fat sucrose diet-fed rats.

Diet-induced obesity is associated to an imbalance in the normal gut microbiota composition. Resveratrol and quercetin, widely known for their health beneficial properties, have low bioavailability, and when they reach the colon, they are targets of the gut microbial ecosystem. Hence, the use of these molecules in obesity might be considered as a potential strategy to modulate intestinal bacterial composition. The purpose of this study was to determine whether trans-resveratrol and quercetin administration could counteract gut microbiota dysbiosis produced by high-fat sucrose diet (HFS) and, in turn, improve gut health. Wistar rats were randomised into four groups fed an HFS diet supplemented or not with trans-resveratrol [15 mg/kg body weight (BW)/day], quercetin (30 mg/kg BW/day) or a combination of both polyphenols at those doses. Administration of both polyphenols together prevented body weight gain and reduced serum insulin levels. Moreover, individual supplementation of trans-resveratrol and quercetin effectively reduced serum insulin levels and insulin resistance. Quercetin supplementation generated a great impact on gut microbiota composition at different taxonomic levels, attenuating Firmicutes/Bacteroidetes ratio and inhibiting the growth of bacterial species previously associated to diet-induced obesity (Erysipelotrichaceae, Bacillus, Eubacterium cylindroides). Overall, the administration of quercetin was found to be effective in lessening HFS-diet-induced gut microbiota dysbiosis. In contrast, trans-resveratrol supplementation alone or in combination with quercetin scarcely modified the profile of gut bacteria but acted at the intestinal level, altering the mRNA expression of tight-junction proteins and inflammation-associated genes.

Circulating irisin and glucose metabolism in overweight/obese women: effects of α-lipoic acid and eicosapentaenoic acid.

Irisin is a myokine/adipokine with potential role in obesity and diabetes. The objectives of the present study were to analyse the relationship between irisin and glucose metabolism at baseline and during an oral glucose tolerance test (OGTT) and to determine the effects of eicosapentaenoic acid (EPA) and/or α-lipoic acid treatment on irisin production in cultured human adipocytes and in vivo in healthy overweight/obese women following a weight loss program. Seventy-three overweight/obese women followed a 30% energy-restricted diet supplemented without (control) or with EPA (1.3 g/day), α-lipoic acid (0.3 g/day) or both EPA + α-lipoic acid (1.3 + 0.3 g/day) during 10 weeks. An OGTT was performed at baseline. Moreover, human adipocytes were treated with EPA (100-200 µM) or α-lipoic acid (100-250 µM) during 24 h. At baseline plasma, irisin circulating levels were positively associated with glucose levels; however, serum irisin concentrations were not affected by the increment in blood glucose or insulin during the OGTT. Treatment with α-lipoic acid (250 µM) upregulated Fndc5 messenger RNA (mRNA) and irisin secretion in cultured adipocytes. In overweight/obese women, irisin circulating levels decreased significantly after weight loss in all groups, while no additional differences were induced by EPA or α-lipoic acid supplementation. Moreover, plasma irisin levels were positively associated with higher glucose concentrations at beginning and at endpoint of the study. The data from the OGTT suggest that glucose is not a direct contributing factor of irisin release. The higher irisin levels observed in overweight/obese conditions could be a protective response of organism to early glucose impairments.

Perinatal maternal feeding with an energy dense diet and/or micronutrient mixture drives offspring fat distribution depending on the sex and growth stage.

Maternal nutrition during pregnancy and lactation influences offspring development and health. Novel studies have described the effects on next generation obesity-related features depending on maternal macro- and micro-nutrient perinatal feeding. We hypothesized that the maternal obesogenic diet during pregnancy and lactation programs an obese phenotype, while maternal micronutrient supplementation at these stages could partially prevent these features. Thus, the aim was to assess the influence of a perinatal maternal feeding with an obesogenic diet enriched in fat and sucrose and a micronutrient supplementation during pregnancy and lactation on offspring growth and obese phenotypical features during life course. Female Wistar rats were assigned to four dietary groups during pregnancy and lactation: control, control supplemented with micronutrients (choline, betaine, folic acid and vitamin B12 ), high-fat sucrose (HFS) and HFS supplemented. At weaning, the offspring were transferred to a chow diet, and weight and fat mass were measured at weeks 3, 12 and 20. At birth, both male and female offspring from mothers fed the obesogenic diet showed lower body weight (-5 and -6%, respectively), while only female offspring weight decreased by maternal micronutrient supplementation (-5%). During lactation, maternal HFS diet was associated with increased body weight, while micronutrient supplementation protected against body weight gain. Whole body fat mass content increased at weeks 3, 12 and 20 (from 16 to 65%) due to maternal HFS diet. Maternal micronutrient supplementation decreased offspring fat mass content at week 3 (-8%). Male offspring showed higher adiposity than females at weeks 12 and 20. In conclusion, maternal HFS feeding during pregnancy and lactation was associated with a low offspring weight at birth and obese phenotypical features during adult life in a sex- and time-dependent manner. Furthermore, maternal methyl donor supplementation protected against body weight gain in male offspring during lactation and in female offspring also during juvenile period.

Supplementation with methyl donors during lactation to high-fat-sucrose-fed dams protects offspring against liver fat accumulation when consuming an obesogenic diet.

Methyl donor supplementation has been reported to prevent obesity-induced liver fat accumulation in adult rats. We hypothesized that this protection could be mediated by perinatal nutrition. For this purpose, we assessed the response to an obesogenic diet (high-fat-sucrose, HFS) during adulthood depending on maternal diet during lactation. Female Wistar rats fed control diet during pregnancy were assigned to four postpartum dietary groups: control, control supplemented with methyl donors (choline, betaine, folic acid, vitamin B12), HFS and HFS supplemented with methyl donors. At weaning, the male offspring was transferred to a chow diet and at week 12th assigned to a control or a HFS diet during 8 weeks. The offspring whose mothers were fed HFS during lactation showed increased adiposity (19%, P<0.001). When fed the HFS diet as adults, offspring whose mothers were HFS supplemented had more body fat (23%, P<0.001) than those from HFS non-supplemented. However, they showed lower liver fat accumulation (-18%, P<0.001). Srebf1, Dnmt1 and Lepr liver mRNA levels increased after adulthood HFS feeding. In those animals HFS fed during adulthood, previous maternal HFS decreased Lepr and Dnmt1 expression levels when compared with c-HFS offspring, while the supplementation of control and HFS-fed dams, respectively, induced higher hepatic Mme and Lepr mRNA levels after adult HFS intake compared with hfs-HFS offspring. In conclusion, maternal HFS diet during lactation influenced the response to an obesogenic diet in the adult progeny. Interestingly, dietary methyl donor supplementation in lactating mothers fed an obesogenic diet reduced liver fat accumulation, but increased adipose tissue storage in adult HFS-fed offspring.

A Fraxinus excelsior L. seeds/fruits extract benefits glucose homeostasis and adiposity related markers in elderly overweight/obese subjects: a longitudinal, randomized, crossover, double-blind, placebo-controlled nutritional intervention study.

PURPOSE: The aim of this study was to investigate the potential benefits of an extract obtained from seeds/fruits of an Oleaceae (Fraxinus excelsior L.) on glucose homeostasis and associated metabolic markers in non-diabetic overweight/obese subjects. MATERIALS AND METHODS: This study was performed in 22 participants (50-80 years-old; BMI 31.0 kg/m(2)). The design was a longitudinal, randomized, crossover, double-blind, placebo-controlled 7-week nutritional intervention. The participants received daily 3 capsules each containing either 333 mg of an extract from Fraxinus excelsior L. seeds (Glucevia(®)) or placebo capsules (control) in a random order for 3 weeks with 1 week of washout between treatments. Moreover, they followed a balanced covert energy-restricted diet (-15% energy). All variables were measured at the beginning and at the end of each period. RESULTS: Compared to baseline, the administration of 1 g of Glucevia(®) for 3 weeks resulted in significantly lower incremental glucose area under the curve (-28.2%; p<0.01), and significantly lower 2 h blood glucose values (-14%; p<0.01) following an oral glucose tolerance test. No significant changes were found in the control group (-7.9% AUC, -1.6% 2h blood glucose). Furthermore, significant differences were found between responses in the control and Glucevia(®) groups with respect to serum fructosamine and plasma glucagon levels (p<0.01 and p<0.05, respectively). Interestingly, administration of Glucevia(®) significantly increased the adiponectin:leptin ratio (p<0.05) and decreased fat mass (p<0.01) compared to control (p<0.05). CONCLUSION: The administration of an extract from Fraxinus excelsior L. seeds/fruits in combination with a moderate hypocaloric diet may be beneficial in metabolic disturbances linked to impaired glucose tolerance, obesity, insulin resistance and inflammatory status, specifically in older adults.

Inverse association between habitual polyphenol intake and incidence of cardiovascular events in the PREDIMED study.

BACKGROUND AND AIMS: Epidemiologic and biological evidence supports an inverse association between polyphenol consumption and the risk of cardiovascular disease (CVD). However, no previous studies have prospectively evaluated the relationship between polyphenol intake and the incidence of CVD in such a comprehensive way. The aim was to evaluate the association between intakes of total polyphenol and polyphenol subgroups, and the risk of major cardiovascular events (myocardial infarction, stroke or death from cardiovascular causes) in the PREDIMED study. METHODS AND RESULTS: The present work is an observational study within the PREDIMED trial. Over an average of 4.3 years of follow-up, there were 273 confirmed cases of CVD among the 7172 participants (96.3%) who completed a validated 137-item food frequency questionnaire (FFQ) at baseline. Polyphenol consumption was calculated by matching food consumption data from the FFQ with the Phenol-Explorer database on polyphenol content of each reported food. After multivariate adjustment, a 46% reduction in risk of CVD risk was observed comparing Q5 vs. Q1 of total polyphenol intake (HR = 0.54; 95% confidence interval [CI] = 0.33-0.91; P-trend = 0.04). The polyphenols with the strongest inverse associations were flavanols (HR = 0.40; CI 0.23-0.72; P-trend = 0.003), lignans (HR = 0.51; CI 0.30-0.86; P-trend = 0.007), and hydroxybenzoic acids (HR = 0.47; CI 0.26-0.86; P-trend 0.02). CONCLUSION: Greater intake of polyphenols, especially from lignans, flavanols, and hydroxybenzoic acids, was associated with decreased CVD risk. Clinical trials are needed to confirm this effect and establish accurate dietary recommendations.

Oxidised LDL levels decreases after the consumption of ready-to-eat meals supplemented with cocoa extract within a hypocaloric diet.

BACKGROUND AND AIMS: Cocoa flavanols are recognised by their favourable antioxidant and vascular effects. This study investigates the influence on health of the daily consumption of ready-to-eat meals supplemented with cocoa extract within a hypocaloric diet, on middle-aged overweight/obese subjects. METHODS AND RESULTS: Fifty healthy male and female middle-aged volunteers [57.26 ± 5.24 years and body mass index (BMI) 30.59 ± 2.33 kg/m(2)] were recruited to participate in a 4 week randomised, parallel and double-blind study. After following 3 days on a low-polyphenol diet, 25 volunteers received meals supplemented with 1.4 g of cocoa extract (645.3 mg of polyphenols) and the other 25 participants received control meals, within a 15% energy restriction diet. On the 4th week of intervention individuals in both dietary groups improved (p < 0.05) anthropometric, body composition, blood pressure and blood biochemical measurements. Oxidised LDL cholesterol (oxLDL), showed a higher reduction (p = 0.030) in the cocoa group. Moreover, myeloperoxidase (MPO) levels decreased only in the cocoa supplemented group (p = 0.007). Intercellular Adhesion Molecule-1 (sICAM-1) decreased significantly in both groups, while Vascular Cell Adhesion Molecule-1 (sVCAM-1) did not present differences after the 4 weeks of intervention. Interestingly, cocoa intake showed a different effect by gender, presenting more beneficial effects in men. CONCLUSIONS: The consumption of cocoa extract as part of ready-to-eat meals and within a hypocaloric diet improved oxidative status (oxLDL) in middle-aged subjects, being most remarkable in males. REGISTRATION NUMBER: Registered at www.clinicaltrials.gov (NCT01596309).

[Software for performing a global phenotypic and genotypic nutritional assessment]. / Programa informático para la realización de una valoración nutricional fenotípica y genotípica integral.

BACKGROUND: The nutritional assessment of a patient needs the simultaneous managing a extensive information and a great number of databases, as both aspects of the process of nutrition and the clinical situation of the patient are analyzed. The introduction of computers in the nutritional area constitutes an extraordinary advance in the administration of nutrition information, providing a complete assessment of nutritional aspects in a quick and easy way. OBJECTIVE: To develop a computer program that can be used as a tool for assessing the nutritional status of the patient, the education of clinical staff, for epidemiological studies and for educational purposes. DESIGN: Based on a computer program which assists the health specialist to perform a full nutritional evaluation of the patient, through the registration and assessment of the phenotypic and genotypic features. The application provides nutritional prognosis based on anthropometric and biochemical parameters, images of states of malnutrition, questionnaires to characterize diseases, diagnostic criteria, identification of alleles associated with the development of specific metabolic illnesses and questionnaires of quality of life, for a custom actuation. The program includes, as part of the nutritional assessment of the patient, food intake analysis, design of diets and promotion of physical activity, introducing food frequency questionnaires, dietary recalls, healthy eating indexes, model diets, fitness tests, and recommendations, recalls and questionnaires of physical activity. RESULT: A computer program performed under Java Swing, using SQLite database and some external libraries such as JfreeChart for plotting graphs. This brand new designed software is composed of five blocks categorized into ten modules named: Patients, Anthropometry, Clinical History, Biochemistry, Dietary History, Diagnostic (with genetic make up), Quality of life, Physical activity, Energy expenditure and Diets. Each module has a specific function which evaluates a different aspect of the nutritional status of the patient. CONCLUSIONS: UNyDIET is a global computer program, customized and upgradeable, easy to use and versatile, aimed to health specialists, medical staff, dietitians, nutritionists, scientists and educators. This tool can be used as a working instrument in programs promoting health, nutritional and clinical assessments as well as in the evaluation of health care quality, in epidemiological studies, in nutrition intervention programs and teaching.

Antecedentes: La evaluación nutricional del paciente requiere del manejo simultáneo de una extensa información y de numerosas bases de datos, ya que se analizan tanto aspectos relacionados con el proceso de la nutrición como la situación y evolución clínica del paciente. Con la introducción de la informática dentro del ámbito nutricional se ha producido un avance extraordinario en la administración de la información, permitiendo la realización de valoraciones exhaustivas del estado nutricional de forma rápida y sencilla. Objetivo: Desarrollar un programa informático que sirva como instrumento para la evaluación del estado nutricional del paciente, la educación del personal clínico, en estudios epidemiológicos y con fines pedagógicos. Diseño: Un programa informático que ayude al especialista de la salud a realizar una evaluación nutricional completa del paciente, mediante el registro y valoración de las características fenotípicas y genotípicas. La aplicación ofrece pronósticos nutricionales basados en parámetros antropométricos y bioquímicos, imágenes de estados de desnutrición, cuestionarios de caracterización de enfermedades, criterios de diagnóstico, identificación de alelos relacionados con el desarrollo de ciertas enfermedades metabólicas y cuestionarios de calidad de vida, para una actuación personalizada. El programa incluye como parte de la valoración nutricional del paciente el análisis de la ingesta alimentaria, la elaboración de dietas y la promoción de la actividad física, introduciendo cuestionarios de frecuencia alimentaria, recordatorios dietéticos, índices de alimentación saludable, dietas modelo, test de condición física así como recomendaciones, recordatorios y cuestionarios de actividad física. Resultado: Un programa informático diseñado mediante el lenguaje de programación Java Swing, usando la base de datos SQLite y algunas librerías externas como JFreeChart para el diseño de gráficos. Está formado por cinco bloques categorizados en diez módulos denominados: Pacientes, Antropometría, Historia clínica, Bioquímica, Historia dietética, Diagnóstico (incluyendo genética), Calidad de vida, Actividad física, Gasto energético y Dietas. Cada módulo tiene una funcionalidad específica que permite valorar un aspecto diferente del estado nutricional del paciente. Conclusiones: UNyDIET es un programa integral, personalizado y actualizable, fácil de usar y versátil, orientado para especialistas de la salud como personal sanitario, dietistas, nutricionistas, científicos y educadores. Esta herramienta se puede utilizar como instrumento de trabajo en programas de promoción de la salud, en valoraciones clínicas y nutricionales, en la evaluación de la calidad asistencial, en estudios epidemiológicos, en programas de intervención nutricional y en docencia.

TNF-alpha promoter methylation in peripheral white blood cells: relationship with circulating TNFα, truncal fat and n-6 PUFA intake in young women.

The aim of this article is to assess the potential relationships between TNFα gene promoter methylation in peripheral white blood cells and central adiposity (truncal fat), metabolic features and dietary fat intake. A group of 40 normal-weight young women (21 ± 3y; BMI 21.0 ± 1.7 kg/m(2)) was included in this cross-sectional study. Anthropometric, biochemical and dietary data were assessed using validated procedures. DNA from white blood cells was isolated and 5-methylcytosine levels of the CpGs sites present in TNFα gene promoter (from -170 to +359 pb) were analyzed by Sequenom EpiTyper. Those women with high truncal fat (≥52.3%) showed lower 5-methylcytosine levels (P<0.05) in the site CpG13 (at position +207) and CpG19 (+317 pb) of the TNFα gene promoter when were compared to women with lower truncal adiposity. The methylation levels of CpG13 were also correlated with circulating TNFα levels, which were higher in those women with greater truncal adiposity. In a linear regression model, truncal fat, HDL-cholesterol, insulin, plasma TNFα, and daily n-6 PUFA intake explained the methylation levels of CpG13 site +207 by 48% and the average of CpG13 and CpG19 by 43% (P<0.001). In conclusion, women with higher truncal fat showed lower methylation levels of TNFα promoter in peripheral white blood cells and higher plasma TNFα concentrations. DNA methylation levels of TNFα promoter were associated with some metabolic features and with n-6 PUFA intake, suggesting a complex nutriepigenomic network in the regulation of this recognized pro-inflammatory marker.

Virgin olive oil supplementation and long-term cognition: the PREDIMED-NAVARRA randomized, trial.

OBJECTIVE: To assess the effect on cognition of a controlled intervention testing Mediterranean diets (MedDiet). DESIGN: Randomized trial after 6.5 years of nutritional intervention. SETTING: Eight primary care centers affiliated to the University of Navarra. PARTICIPANTS: A random subsample of 285 participants (95 randomly allocated to each of 3 groups) of the PREDIMED-NAVARRA trial. All of them were at high vascular risk (44.8% men, 74.1±5.7 years at cognitive evaluation). INTERVENTIONS: Nutritional intervention comparing two MedDiets (supplemented with extra-virgin olive oil [EVOO] or mixed nuts) versus a low-fat control diet. Participants received intensive education to increase adherence to the intended intervention. Participants allocated to the MedDiet groups received EVOO (1 l/week) or 30 g/day of mixed nuts. Dietary habits were evaluated using a validated 137-item food frequency questionnaire (FFQ). Additionally, adherence to MedDiet was appraised using a 14-item questionnaire both at baseline and yearly thereafter. MEASUREMENTS: Cognitive performance as a main outcome and cognitive status (normal, mild cognitive impairment [MCI] or dementia) as a secondary outcome were evaluated by two neurologists blinded to group assignment after 6.5 years of nutritional intervention. RESULTS: Better post-trial cognitive performance versus control in all cognitive domains and significantly better performance across fluency and memory tasks were observed for participants allocated to the MedDiet+EVOO group. After adjustment for sex, age, education, apolipoprotein E genotype, family history of cognitive impairment/dementia, smoking, physical activity, body mass index, hypertension, dyslipidaemia, diabetes, alcohol and total energy intake, this group also showed lower MCI (OR=0.34 95% CI: 0.12-0.97) compared with control group. Participants assigned to MedDiet+Nuts group did not differ from controls. CONCLUSION: A long-term intervention with an EVOO-rich MedDiet resulted in a better cognitive function in comparison with a control diet. However, non-significant differences were found for most cognitive domains. Participants allocated to an EVOO-rich MedDiet had less MCI than controls.

Predictive factors for mortality in patients with methicillin-resistant Staphylococcus aureus bloodstream infection: impact on outcome of host, microorganism and therapy.

Mortality related to methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) remains high, despite changes in the epidemiology. To analyze the current predictive factors for mortality we conducted a prospective study in a large cohort of patients with MRSA-BSI from 21 Spanish hospitals. Epidemiology, clinical data, therapy and outcome were recorded. All MRSA strains were analysed, including susceptibility to antibiotics and molecular characterization. Vancomycin MICs (V-MIC) were tested by the E-test and microdilution methods. Time until death was the dependent variable in a Cox regression analysis. Overall, 579 episodes were included. Acquisition was nosocomial in 59% and vascular catheter was the most frequent source (38%). A dominant PFGE genotype was found in 368 (67%) isolates, which belonged to Clonal Complex (CC)5 and carried SCCmecIV and agr2. Microdilution V-MIC50 and V-MIC90 were 0.7 and 1.0 mg/L, respectively. Initial therapy was appropriate in 66% of episodes. Overall mortality was observed in 179 (32%) episodes. The Cox-regression analysis identified age >70 years (HR 1.88), previous fatal disease (HR 2.16), Pitt score >1 (HR 3.45), high-risk source (HR 1.85) and inappropriate initial treatment (HR 1.39) as independent predictive factors for mortality. CC5 and CC22 (HR 0.52 and 0.45) were associated with significantly lower mortality rates than CC8. V-MIC ≥1.5 did not have a significant impact on mortality, regardless of the method used to assess it.

Essential oils from clove affect growth of Penicillium species obtained from lemons.

Continuous use of fungicides to control citrus postharvest diseases has led to increasing resistant strains of pathogens. Since the appearance of fungicide resistance has become an important factor in limiting the efficacy fungicide treatments, new studies have been needed in order to improve control methods. There is a growing consumer's concern about the possible harmful effects of synthetic fungicides on the human health and the environment. Alternatives to synthetic fungicides for citrus decay control include essential oils. These compounds are known for their natural components and they are searched for potential bioactive plant extracts against fungi. In this study, two isolates of P. digitatum and P. italicum each were collected from lemon fruits affected by green and blue mould, respectively. Isolates were purified in potato dextrose agar (PDA) in order to separate the two species which we are demonstrated that they commonly grow together in nature. In vitro assays, in which isolates were grown at 26 degrees C on Petri dishes containing PDA for up to 17 days, were carried out by pouring several doses of essential oils from clove (Syzygium aromaticum L.) on PDA to obtain the following concentrations (v/v): 1.6; 8, 40, 200 and 500 microL L(-1) + tween 80 (0.1 mL L(-1)). Mycelial growth curves and growth, conidiation, mass of aerial mycelium and conidial size were measured. Penicillium isolates showed a slight degree of variability in their growth kinetics, depending on the isolate. 500 microL L(-1) inhibited the growth of all the isolates, whereas concentrations lower than 40 microL L(-1) slightly increased the growth. 200 microL L(-1) reduced both growth and conidiation in all isolates. Aerial mycelium of P. digitatum was not affected by clove, whereas reduced the mass of mycelium of P. italicum at concentrations higher than 8 microL L(-1). In vivo experiment was carried out inoculating a drop of an extract of conidia with a hypodermal syringe though a puncture reaching the albedo. Fruits inoculated were stored at 23 degrees C and 74% RH for 25 days. Imazalil was used as a fungicide control. The treatment composed by 25% of commercial dose of imazalil plus 200 microL L(-1) of clove was the best to reduce decay until 10% of commercial dose of imazalil. In addition, this experimental treatment significantly reduced conidiation, therefore could inhibit the decay dispersion during storage. This suggests that treatments based on both imazalil and clove essential oils may have potential effect in controlling both green and blue mould.

Dietary supplementation with methyl donors reduces fatty liver and modifies the fatty acid synthase DNA methylation profile in rats fed an obesogenic diet.

Non-alcoholic fatty liver disease (NAFLD) is one of the first hepatic manifestations of metabolic syndrome, whose progression can lead to cirrhosis and hepatic carcinoma. Interestingly, methyl donor supplementation could improve obesogenic diet-induced hepatic triglyceride accumulation. The aim of this research is to describe methyl donor effects on a high-fat-sucrose (HFS) diet in both sexes and epigenetic changes induced on fatty acid synthase (FASN) promoter methylation pattern as well as gene expression of NAFLD key metabolic genes. Twenty-four male and 28 female Wistar rats were assigned to three dietary groups: control, HFS, and HFS supplemented with methyl donors (choline, betaine, vitamin B12, and folic acid). After 8 weeks of treatment, somatic, biochemical, mRNA, and epigenetic measurements were performed. Rats fed the HFS diet presented an overweight phenotype and alterations in plasma biochemical measurements. Methyl donor supplementation reverted the HFS-diet-induced hepatic triglyceride accumulation. Analysis of FASN promoter cytosine methylation showed changes in both sexes due to the obesogenic diet at -1,096, -780, -778, and -774 CpG sites with respect to the transcriptional start site. Methyl donor supplementation modified DNA methylation at -852, -833, -829, -743, and -733 CpGs depending on the sex. RT-PCR analysis confirmed that FASN expression tended to be altered in males. Our findings reinforce the hypothesis that methyl donor supplementation can prevent hepatic triglyceride accumulation induced by obesogenic diets in both sexes. Changes in liver gene expression profile and epigenetic-mediated mechanisms related to FASN DNA hypermethylation could be involved in methyl donor-induced NAFLD improvement.