Effects of calcium carbonate inclusion in low fishmeal diets on growth, gastrointestinal pH, digestive enzyme activity and gut bacterial community of European sea bass (Dicentrarchus labrax L.) juveniles

Fishmeal (FM) possesses one of the highest buffering capacities in comparison to most alternative vegetable aquafeed ingredients and its decreasing content in current formulations might affect the ideal gastrointestinal environment for digestive enzyme action and gut bacterial community of carnivorous fish species. A study was undertaken, therefore, to assess growth response, gastrointestinal pH, digestive enzyme activity and gut bacterial community of European sea bass (Dicentrarchus labrax L.) juveniles fed low FM diets (10% FM) with or without a feed buffering additive, calcium carbonate (FM10 + B and FM10, respectively) in comparison to a standard FM diet (20% FM, FM20). Three isonitrogenous and isolipidic extruded diets were fed to triplicate fish groups of 80 individuals (initial weight: 23 g) to overfeeding over 64 days. No significant differences due to low FM dietary levels were observed in final body weight, specific growth rate, feed intake, feed and protein efficiency. Low FM diet did not affect gastrointestinal pH in the stomach, anterior intestine, mid-intestine and hindgut at 0, 4, 8 and 12 hours post meal (hpm) while the inclusion of calcium carbonate in low FM diet seems to slightly increase the pH in the hindgut at 12 hpm. The absence of significant differences of pepsin, chymotrypsin, amylase and lipase activity suggests a comparable digestive efficiency among treatments although trypsin activity was slightly reduced in low FM diets after 4 hpm. Decreasing FM content seems to exert an effect on the overall gut bacterial community analysed by next-generation sequencing even if no significant effects on specific bacterial component were detected. The gut bacterial community in all the treatments was particularly rich in lactic acid bacteria such as Lactobacillus spp. which may provide important beneficial functions for the host and be associated with a healthy intestinal epithelium. According to the results, increasing the feed buffering capacity does not seem to improve digestive conditions while it is feasible to include 10% FM dietary level in practical formulation for European sea bass juveniles without negatively affecting growth, feed efficiency and digestive luminal conditions.info:eu-repo/semantics/publishedVersio

Vegetable and fruit intakes are associated with hs-CRP Levels in pre-pubertal girls

The influence of diet on inflammation in children remains unclear. We aimed to analyze the influence of diet on high-sensitivity C-reactive protein (hs-CRP) levels in a pre-pubertal population free of other influences that may affect hs-CRP levels. We determined hs-CRP levels in 571 six- to eight-year-old children using an hs-CRP ELISA kit. Information on food and nutrient intake was obtained through a food-frequency questionnaire. Overall dietary quality was assessed using the Healthy Eating Index (HEI). We found that girls in the highest tertile of hs-CRP levels had a higher intake of saturated fatty acid, and lower intakes of fiber and vitamin E and a lower HEI score when compared to those in tertiles 1 and 2. We also observed a significant decrease in fruit and vegetable intakes by hs-CRP tertile. Factor analysis showed that a dietary pattern that was loaded most strongly with vegetable, fruit, fiber and vitamin A and E intakes correlated negatively (−0.132, p < 0.05) with hs-CRP. No such association was found in boys. In conclusion, our data show that girls with a poorer quality diet show higher hs-CRP levels already at a pre-pubertal age

Impact of deoxynivalenol on rainbow trout: Growth performance, digestibility, key gene expression regulation and metabolism

The impact of deoxynivalenol (DON) on rainbow trout, Oncorhynchus mykiss, is mainly characterised by impaired growth performance and reduced feed intake, usually with the total absence of any visible clinical signs. Despite the high concentrations of DON in the present study (up to 11,412 ± 1141 μg kg−1), no clinical signs (except anorexia at the higher DON dosage) were observed, which confirms the difficulties of diagnosing DON ingestion. Compared to the control group, the proteolytic enzyme activities (pepsin, trypsin and chymotrypsin) in trout were altered by DON ingestion. However, it was not clear if the observed impact on digestive enzymes was due to the direct action of DON, or a consequence of the lower feed intake determined for DON-treated animals. The impact of DON on the abundance of specific measured mRNA transcripts was unexpected with higher expression levels for insulin-like growth factors, igf1 and igf2, which are directly related to elevated insulin levels in plasma. This can also in part be influenced by the trypsin activity and by npy, given its higher mRNA expression levels. The apparent digestibility of dry matter, protein and energy was not affected by dietary levels of DON, however, nutrient retention, protein, fat and energy retention were significantly affected in animals fed DON. Adenylate cyclase-activating polypeptide (PACAP) expression seems to play an important role in controlling feed intake in DON fed trout. In the present study, we have shown for the first time that DON is metabolized to DON-3-sulfate in trout. DON-3-sulfate is much less toxic than DON, which helps to explain the lack of clinical signs in fish fed DON. Being a novel metabolite identified in trout makes it a potential biomarker of DON exposure. Suppression of appetite due to DON contamination in feeds might be a defense mechanism in order to decrease the exposure of the animal to DON, therefore reducing the potential negative impacts of DON

Immune response generated with the administration of autologous dendritic cells pulsed with an allogenic tumoral cell lines lysate in patients with newly diagnosed DIPG

Background and objective. Diffuse intrinsic pontine glioma (DIPG) is a lethal brainstem tumor in children. Dendritic cells (DCs) have T-cell stimulatory capacity and, therefore, potential antitumor activity for disease control. DCs vaccines have been shown to reactivate tumor-specific T cells in both clinical and pre-clinical settings. We designed a phase Ib immunotherapy (IT) clinical trial with the use of autologous dendritic cells (ADCs) pulsed with an allogeneic tumors cell-lines lysate (ATCL) in patients with newly diagnosed DIPG after irradiation (RT). Methods. Nine patients with newly diagnosed DIPG met enrollment criteria. Autologous dendritic cell vaccines (ADCV) were prepared from monocytes obtained by leukapheresis. Five ADCV doses were administered intradermally during induction phase. In the absence of tumor progression, patients received 3 boosts of tumor lysate every three months during the maintenance phase. Results. Vaccine fabrication was feasible in all patients included in the study. Non-specific KLH (9/9 patients) and specific (8/9 patients) antitumor response was identified by immunologic studies in peripheral blood mononuclear cells (PBMC). Immunological responses were also confirmed in the T lymphocytes isolated from the cerebrospinal fluid (CSF) of 2 patients. Vaccine administration resulted safe in all patients treated with this schema. Conclusions. These preliminary results demonstrate that ADCV preparation is feasible, safe and generate a DIPG-specific immune response detected in PBMC and CSF. This strategy shows a promising backbone for future schemas of combination immunotherapy

Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.This work was supported by the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Health (FIS; PI16/00425 and PI19/00321), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER, 06/07/0036), IIS-FJD BioBank (PT13/0010/0012), Comunidad de Madrid (CAM, RAREGenomics Project, B2017/BMD-3721), European Regional Development Fund (FEDER), the Organización Nacional de Ciegos Españoles (ONCE), Fundación Ramón Areces, Fundación Conchita Rábago and the University Chair UAM-IIS-FJD of Genomic Medicine. Irene Perea-Romero is supported by a PhD fellowship from the predoctoral Program from ISCIII (FI17/00192). Ionut F. Iancu is supported by a grant from the Comunidad de Madrid (CAM, PEJ-2017-AI/BMD7256). Marta del Pozo-Valero is supported by a PhD grant from the Fundación Conchita Rábago. Berta Almoguera is supported by a Juan Rodes program from ISCIII (JR17/00020). Pablo Minguez is supported by a Miguel Servet program from ISCIII (CP16/00116). Marta Corton is supported by a Miguel Servet program from ISCIII (CPII17/00006). The funders played no role in study design, data collection, data analysis, manuscript preparation and/or publication decisions

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Desafíos de la inclusión en la educación universitaria desde la praxis educativa transformadora

The general objective of the research was to analyze the challenges of inclusion in university education from the transformative educational praxis. The methodology used was from the positivist paradigm and quantitative perspective, through the search, collection and critical analysis of documents, bibliographic references and refereed scientific works, based primarily on written documents such as refereed and scientific works, proposing a detailed review and reflection to obtain the necessary data for the theoretical development. As a result, it was determined that the term inclusion in university education is reduced by some to the inclusion in the university education system of vulnerable people or people with disabilities, while others propose the comprehensiveness of the incorporation of people from the cultural, ethnic, sexual and gender variety. It is concluded that social changes and evolutions demand the implementation and promotion of equity with facts of individual and group inclusion.El objetivo general de la investigación fue analizar los desafíos de la inclusión en la educación universitaria desde la praxis educativa transformadora. La metodología utilizada fue desde el paradigma positivista y perspectiva cuantitativa, a través de la búsqueda, recolección y análisis crítico documental, referencial bibliográfico y trabajos científicos arbitrados, se basó primordialmente en documentos escritos como trabajos arbitrados y científicos, planteándose una revisión y reflexión detallada obteniendo los datos necesarios para el desarrollo teórico. Como resultado se determinó que el término inclusión en la educación universitaria por cuanto unos lo reducen a incluir en el sistema educativo universitario a las personas vulnerables o con alguna discapacidad, mientras que otros plantean la integralidad de la incorporación de las personas desde a la variedad, cultural, étnica, sexual y género. Se concluye que los cambios y evoluciones sociales demandan que se implementen y promueva la equidad con hechos de inclusión individual y grupal

Plasma Retinol Levels and High-Sensitivity C-Reactive Protein in Prepubertal Children

The relationship between C-reactive protein (CRP) levels and plasma antioxidants has been established in adults. However, the association has been rarely investigated in healthy children. Thus, we examined the cross-sectional association of high-sensitivity CRP (hs-CRP) levels with fat-soluble plasma antioxidant concentrations in a cohort of healthy prepubertal children. We determined hs-CRP levels in 543 healthy six&ndash;eight-year-old children using a high-sensitivity CRP enzyme-linked immuno sorbent assay (ELISA) kit. The plasma concentrations of lipids, apolipoproteins and lipid-soluble antioxidants (&alpha;-tocopherol, &gamma;-tocopherol, lycopene, &alpha;-carotene, &beta;-carotene and retinol) were determined using standardized methods. Pearson correlation analysis showed significant correlations between plasma hs-CRP and &alpha;-carotene and retinol concentrations. After adjusting by sex, body mass index (BMI) and lipid levels, only the association with retinol remains significant, with children in the highest hs-CRP tertile group (hs-CRP &ge; 0.60 mg/dL) showing significantly lower levels of retinol than those from the tertiles 1 and 2. A stepwise linear regression selected retinol, BMI, apo A-I and sex as predictors of hs-CRP levels, in a model explaining 19.2% of the variability of hs-CRP. In conclusion, in healthy prepubertal children, after adjusting by sex, BMI and lipid levels, hs-CRP concentrations were highly associated with plasma retinol, which is transported in blood bound to retinol-binding protein but were not associated with the lipoprotein-bound antioxidants

Macroeconomia-AF66-201202

La Macroeconomía nos afecta a todos ya sea en el hogar en la empresa en el país y en el mundo en general es por eso que toda persona instruída debe tener un conocimiento básico del tema; éste nos ayuda a comprender las repercusiones que tienen en la empresa las principales variables macroeconómicas como son el PBI inflación empleo déficit fiscal balanza de pagos etc