Dietary and Lifestyle Patterns in the Spanish Pediatric Population (One to <10 Years Old): Design, Protocol, and Methodology of the EsNuPI Study

The interest in a healthy diet and lifestyle during the early stages of life increased, pointing out its role in the development of noncommunicable chronic diseases throughout adult life. Dietary habits and dietary patterns begin to be established in early childhood and persist during adulthood. Therefore, the EsNuPI ("Nutritional Study in Spanish Pediatric Population") study aims to depict the dietary patterns, physical activity, and sedentary behaviors in Spanish children aged from one to 50,000 inhabitants, stratified by Nielsen areas. Participants were involved in one face-to-face survey, followed by a telephone survey after at least one week. Information about dietary intake and habits was obtained using a quantitative food frequency questionnaire and two 24-h dietary recalls. Physical activity and sedentary behaviors were registered using a specific questionnaire based on a seven-day record. Data were processed and stratified by categorical variables to be statistically analyzed in order to meet the study objectives. This study is the first of its kind in a Spanish reference population of this age range and the first to evaluate whether the consumption of adapted milk formulas and dairy products is associated with healthier dietary patterns and better diet quality and lifestyles in this group

Energy Intake, Macronutrient Profile and Food Sources of Spanish Children Aged One to <10 Years—Results from the EsNuPI Study

Abstract: The present study aimed to assess energy intake, nutrient profile and food sources in Spanish children participating in the EsNuPI (“Estudio Nutricional en Población Infantil Española”) study. Plausibility of energy intake and adequacy of nutrient intakes to international recommendations were analyzed in a final sample of 1448 subjects (728 boys and 720 girls) and one group representative of the 1 to <10 years old urban Spanish children (reference sample (n = 707)) who consumed milk and one of the same age who consumed adapted milk over the last year (adapted milk consumers sample (n = 741)) were compared. Both groups completed data of a face-to-face and a telephone 24-h dietary recalls. Both the reference and the adapted milk consumers samples reported an adequate daily energy intake (1503 kcal/day and 1404 kcal/day); and a high contribution to total energy from protein (16.5% and 15.6%) and fat (36.5% and 35.9%). Also, a high percentage of children from both samples were below the lower limit of the recommendations for carbohydrates (47.8% and 39.3%). As the percentage of plausible energy reporters was high for both groups (84.7% and 83.5%, respectively), data for the whole sample were analyzed. Milk and dairy, cereals, meat and derived products, fats and oils, bakery and pastry, fruits and vegetables contributed to about 80% of the total energy intake in both groups. However, the reference sample reported significantly more contribution to energy from cereals, meat and meat products, bakery and pastry and ready to cook/eat foods; meanwhile, the adapted milk consumers sample reported significantly more energy from milk and dairy products, fruits and eggs. Those results suggest that adapted milk consumers have better adherence to the food-based dietary guidelines. Further analyses are warranted to characterize food patterns and the quality of the diet in the EsNuPI study population

Dietary Intake, Nutritional Adequacy and Food Sources of Total Fat and Fatty Acids, and Relationships with Personal and Family Factors in Spanish Children Aged One to <10 Years: Results of the EsNuPI Study

We aimed to determine the usual intake of total fat, fatty acids (FAs), and their main food sources in a representative cohort of the Spanish pediatric population aged 1 to <10 years (n = 707) who consumed all types of milk and an age-matched cohort who consumed adapted milk over the last year (including follow-on formula, toddler’s milk, growing-up milk, and fortified and enriched milks) (n = 741) who were participants in the EsNuPI study (in English, Nutritional Study in the Spanish Pediatric Population). Dietary intake, measured through two 24 h dietary recalls, was compared to the European Food Safety Authority (EFSA) and the Food and Agriculture Organization of the United Nations (UN-FAO) recommendations. Both cohorts showed a high intake of saturated fatty acids (SFAs), according to FAO recommendations, as there are no numerical recommendations for SFAs at EFSA. Also, low intake of essential fatty acids (EFAs; linoleic acid (LA) and α-linolenic acid (ALA)) and long-chain polyunsaturated fatty acids (LC-PUFA) of the n-3 series, mainly docosahexaenoic acid (DHA) were observed according to EFSA and FAO recommendations. The three main sources of total fat and different FAs were milk and dairy products, oils and fats, and meat and meat products. The consumption of adapted milk was one of the main factors associated with better adherence to the nutritional recommendations of total fat, SFAs, EFAs, PUFAs; and resulted as the main factor associated with better adherence to n-3 fatty acids intake recommendations. Knowledge of the dietary intake and food sources of total fat and FAs in children could help in designing and promoting effective and practical age-targeted guidelines to promote the consumption of EFA- and n-3 PUFA-rich foods in this stage of life

Clustering of Dietary Patterns and Lifestyles among Spanish Children in the EsNuPI Study

Dietary patterns (DPs) are known to be tied to lifestyle behaviors. Understanding DPs and their relationships with lifestyle factors can help to prevent children from engaging in unhealthy dietary practices. We aimed to describe DPs in Spanish children aged 1 to <10 years and to examine their associations with sociodemographic and lifestyle variables. The consumption of toddler and young children milk formulas, enriched and fortified milk within the Spanish pediatric population is increasing, and there is a lack of evidence whether the consumption of this type of milk is causing an impact on nutrient intakes and if they are helping to reach the nutrient recommendations. Within the Nutritional Study in the Spanish Pediatric Population (EsNuPI), we considered two study cohorts and three different age groups in three year-intervals in each of them. The study cohort included 740 children in a representative sample of the urban non-vegan Spanish population and 772 children in a convenience cohort of adapted milk consumers (AMS) (including follow-on formula, toddler’s milk, growing up milk, and fortified and enriched milks) who provided information about sociodemographics, lifestyle, and dietary habits; a food frequency questionnaire was used for the latter. Principal component analysis was performed to identify DPs from 18 food groups. Food groups and sociodemographic/lifestyle variables were combined through a hierarchical cluster algorithm. Three DPs predominated in every age group and study sample: a palatable energy-dense food dietary pattern, and two Mediterranean-like DPs. However, children from the AMS showed a predominant dietary pattern markedly related to the Mediterranean diet, with high consumption of cereals, fruits and vegetables, as well as milk and dairy products. The age of children and certain lifestyle factors, namely level of physical activity, parental education, and household income, correlated closely with the dietary clusters. Thus, the findings provide insight into designing lifestyle interventions that could reverse the appearance of unhealthy DPs in the Spanish child population

Usual dietary intake, nutritional adequacy and food sources of calcium, phosphorus, magnesium and vitamin D of spanish children aged one to dagger

Bone problems in the population begin to be establish in childhood. The present study aims to assess the usual calcium, phosphorus, magnesium, and vitamin D intakes, along with the food sources of these nutrients, in Spanish children participating in the EsNuPI (Estudio Nutricional en Población Infantil Española) study. Two 24 h dietary recalls were applied to 1448 children (1 to <10 years) divided into two sub-samples: one reference sample (RS) of the general population [n = 707] and another sample which exclusively included children consuming enriched or fortified milks, here called “adapted milks” (AMS) [n = 741]. Estimation of the usual intake shows that nutrient intake increased with age for all nutrients except vitamin D. Using as reference the Dietary Reference Values from the European Food Safety Authority (EFSA), calcium and magnesium intakes were found to be below the average requirement (AR) and adequate intake (AI), respectively, in a considerable percentage of children. Furthermore, phosphorus exceeded the AI in 100% of individuals and vitamin D was lower than the AI in almost all children studied. The results were very similar when considering only plausible reporters. When analyzing the food sources of the nutrients studied, milk and dairy products contributed the most to calcium, phosphorus, magnesium, and vitamin D. Other sources of calcium were cereals and vegetables; for phosphorus: meat, meat products, and cereals; for magnesium: cereals and fruits; and, for vitamin D: fish and eggs. These results highlight the desirability of improving the intake concerning these nutrients, which are involved in bone and metabolic health in children. The AMS group appeared to contribute better to the adequacy of those nutrients than the RS group, but both still need further improvement. Of special interest are the results of vitamin D intakes, which were significantly higher in the AMS group (although still below the AI), independent of age

Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNA

The screening of the BCR::ABL1 kinase domain (KD) mutation has become a routine analysis in case of warning/failure for chronic myeloid leukemia (CML) and B-cell precursor acute lymphoblastic leukemia (ALL) Philadelphia (Ph)-positive patients. In this study, we present a novel DNA-based next-generation sequencing (NGS) methodology for KD ABL1 mutation detection and monitoring with a 1.0E−4 sensitivity. This approach was validated with a well-stablished RNA-based nested NGS method. The correlation of both techniques for the quantification of ABL1 mutations was high (Pearson r = 0.858, p < 0.001), offering DNA-DeepNGS a sensitivity of 92% and specificity of 82%. The clinical impact was studied in a cohort of 129 patients (n = 67 for CML and n = 62 for B-ALL patients). A total of 162 samples (n = 86 CML and n = 76 B-ALL) were studied. Of them, 27 out of 86 harbored mutations (6 in warning and 21 in failure) for CML, and 13 out of 76 (2 diagnostic and 11 relapse samples) did in B-ALL patients. In addition, in four cases were detected mutation despite BCR::ABL1 < 1%. In conclusion, we were able to detect KD ABL1 mutations with a 1.0E−4 sensitivity by NGS using DNA as starting material even in patients with low levels of disease.Tis project was funded in part by CRIS CANCER FOUNDATION

Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFN-α production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues