Adaptación del classroom observation code en la población escolar para la evaluación de la hiperactividad infantil

En: Anuario de Psicología. ISSN. 0066-5126 n. 1 (1991), p. 55-6

Hepatocellular carcinoma risk-stratification based on ASGR1 in circulating epithelial cells for cancer interception

Purpose: Lack of diagnostic and prognostic biomarkers in hepatocellular carcinoma impedes stratifying patients based on their risk of developing cancer. The aim of this study was to evaluate phenotypic and genetic heterogeneity of circulating epithelial cells (CECs) based on asialoglycoprotein receptor 1 (ASGR1) and miR-122-5p expression as potential diagnostic and prognostic tools in patients with hepatocellular carcinoma (HCC) and liver cirrhosis (LC). Methods: Peripheral blood samples were extracted from LC and HCC patients at different disease stages. CECs were isolated using positive immunomagnetic selection. Genetic and phenotypic characterization was validated by double immunocytochemistry for cytokeratin (CK) and ASGR1 or by in situ hybridization with miR-122-5p and CECs were visualized by confocal microscopy. Results: The presence of CECs increased HCC risk by 2.58-fold, however, this was only significant for patients with previous LC (p = 0.028) and not for those without prior LC (p = 0.23). Furthermore, the number of CECs lacking ASGR1 expression correlated significantly with HCC incidence and absence of miR-122-5p expression (p = 0.014; r = 0.23). Finally, overall survival was significantly greater for patients at earlier cancer stages (p = 0.018), but this difference was only maintained in the group with the presence of CECs (p = 0.021) whereas progression-free survival was influenced by the absence of ASGR1 expression. Conclusion: Identification and characterization of CECs by ASGR1 and/or miR- 122-5p expression may be used as a risk-stratification tool in LC patients, as it was shown to be an independent prognostic and risk-stratification marker in LC and early disease stage HCC patients.Regional Ministry of Health of AndalusiaMinistry of Economy, Competitiveness, Enterprises and Universities PC-0522-2016 PC-0267-2017 PC-0033-2017Health Institute Carlos III (ISCIII) DOC_01682 CD18/0012

Deep Phenotypic Characterisation of CTCs by Combination of Microfluidic Isolation (IsoFlux) and Imaging Flow Cytometry (ImageStream)

Ines Aznar-Peralta holds a "Garantia Juvenil" fellowship (contract number 8040), and M. Carmen Garrido-Navas has a postdoctoral fellowship funded by the Ministry of Economy, Competitiveness, Enterprises and Universities (DOC_01682).The isolation of circulating tumour cells (CTCs) in colorectal cancer (CRC) mostly relies on the expression of epithelial markers such as EpCAM, and phenotypic characterisation is usually performed under fluorescence microscopy with only one or two additional markers. This limits the ability to detect different CTC subpopulations based on multiple markers. The aim of this work was to develop a novel protocol combining two platforms (IsoFluxTM and ImageStream®X) to improve CTC evaluation. Cancer cell lines and peripheral blood from healthy donors were used to evaluate the efficiency of each platform independently and in combination. Peripheral blood was extracted from 16 early CRC patients (before loco-regional surgery) to demonstrate the suitability of the protocol for CTC assessment. Additionally, peripheral blood was extracted from nine patients one month after surgery to validate the utility of our protocol for identifying CTC subpopulation changes over time. Results: Our protocol had a mean recovery efficiency of 69.5% and a limit of detection of at least four cells per millilitre. We developed an analysis method to reduce noise from magnetic beads used for CTC isolation. CTCs were isolated from CRC patients with a median of 37 CTCs (IQ 13.0–85.5) at baseline. CTCs from CRC patients were significantly (p < 0.0001) larger than cytokeratin (CK)-negative cells, and patients were stratified into two groups based on BRAFV600E and PD-L1 expression on CK-positive cells. The changes observed over time included not only the number of CTCs but also their distribution into four different subpopulations defined according to BRAFV600E and PD-L1 positivity. We developed a novel protocol for semi-automatic CTC isolation and phenotypic characterisation by combining two platforms. Assessment of CTCs from early CRC patients using our protocol allowed the identification of two clusters of patients with changing phenotypes over time."Garantia Juvenil" fellowship 8040Ministry of Economy, Competitiveness, Enterprises and Universities DOC_0168

Identification of hereditary breast and ovarian cancer germline variants in Granada (Spain): NGS perspective

Funding for open access charge: Universidad de Granada/CBUA. Maria Molina-Zayas has been a recipient of the 2018 AEFA Post-residency Grant (Spanish Association of Clinical Laboratory) and Dr. Carmen Garrido-Navas holds a postdoctoral fellowship from the Ministry of Economy, Competitiveness, Enterprises and Universities (DOC_01682).The aim of this study was to assess the prevalence of germline variants in cancer-predisposing genes by either targeted (BRCA1/2) or multigene NGS panel in a high-risk Hereditary Breast and Ovarian Cancer (HBOC) cohort. Samples from 824 Caucasian probands were retrospectively collected and the impact of genetic diagnosis and genetic variants epidemiology in this cohort was evaluated. Performance of risk-reducing prophylactic measures, such as prophylactic mastectomy and/or prophylactic oophorectomy, was assessed through clinical follow-up of patients with a positive genetic result. Pathogenic variants predisposing to HBOC were identified in 11.9% (98/824) individuals at BRCA2 (47/98), BRCA1 (24/98), PALB2 (8/51), ATM (7/51), CHEK2 (6/51) MSH6, (2/51), RAD51C (2/51) and TP53 (2/386). Of them, 11 novel pathogenic variants and 12 VUS were identified, characterized, and submitted to ClinVar. Regarding clinical impact, the risk of developing basal or Her2 breast cancer was increased 15.7 times or 37.5 times for BRCA1 and MSH6 pathogenic variants respectively. On the contrary, the risk of developing basal or luminal A breast cancer was reduced to 81% or 77% for BRCA2 and BRCA1 pathogenic variants, respectively. Finally, 53.2% of individuals testing positive for class IV/V variants underwent prophylactic surgery (mastectomy, oophorectomy or both) being significantly younger at the cancer diagnosis than those undertaking prophylactic measures (p = 0.008). Of them, 8 carried a pathogenic/likely pathogenic variant in other genes different from BRCA1 and BRCA2, and the remaining (46.7%) decided to continue with clinical follow-up. No differences in pathogenicity or risk of developing cancer were found for BRCA1/2 between targeted and multigene sequencing strategies; however, NGS was able to resolve a greater proportion of high-risk patients.Universidad de Granada/CBUA2018 AEFA Post-residency Grant (Spanish Association of Clinical Laboratory)Ministry of Economy, Competitiveness, Enterprises and Universities DOC_0168

Maternal, fetal and perinatal alterations associated with obesity, overweight and gestational diabetes: an observational cohort study (PREOBE)

Abstract Background: Maternal overweight, obesity, and gestational diabetes (GD) have been negatively associated with offspring development. Further knowledge regarding metabolic and nutritional alterations in these mother and their offspring are warranted. Methods: In an observational cohort study we included 331 pregnant women from Granada, Spain. The mothers were categorized into four groups according to BMI and their GD status; overweight (n:56), obese (n:64), GD (n:79), and healthy normal weight controls (n:132). We assessed maternal growth and nutritional biomarkers at 24 weeks (n = 269), 34 weeks (n = 310) and at delivery (n = 310) and the perinatal characteristics including cord blood biomarkers. Results: Obese and GD mothers had significantly lower weight gain during pregnancy and infant birth weight, waist circumference, and placental weight were higher in the obese group, including a significantly increased prevalence of macrosomia. Except for differences in markers of glucose metabolism (glucose, HbA1c, insulin and uric acid) we found at some measures that overweight and/or obese mothers had lower levels of transferrin saturation, hemoglobin, Vitamin B12 and folate and higher levels of C-reactive protein, erythrocyte sedimentation rate, ferritin, and cortisol. GD mothers had similar differences in hemoglobin and C-reactive protein but higher levels of folate. The latter was seen also in cord blood. Conclusions: We identified several metabolic alterations in overweight, obese and GD mothers compared to controls. Together with the observed differences in infant anthropometrics, these may be important biomarkers in future research regarding the programming of health and disease in children. Trial registration: The trial was registered at clinicaltrials.gov, identifier (NCT01634464). Keywords: Pregnancy, Maternal overweight, Maternal obesity, Gestational diabetes, Offspring, Fetal nutrition, Early programming, Vitamin B12, Folate, Iron status, Glucose metabolis

Changes in population age-structure obscure the temperature-size rule in marine cyanobacteria

The temperature-size Rule (TSR) states that there is a negative relationship between ambient temperature and body size. This rule has been independently evaluated for different phases of the life cycle in multicellular eukaryotes, but mostly for the average population in unicellular organisms. We acclimated two model marine cyanobacterial strains (Prochlorococcus marinus MIT9301 and Synechococcus sp. RS9907) to a gradient of temperatures and measured the changes in population age-structure and cell size along their division cycle. Both strains displayed temperature-dependent diel changes in cell size, and as a result, the relationship between temperature and average cell size varied along the day. We computed the mean cell size of new-born cells in order to test the prediction of the TSR on a single-growth stage. Our work reconciles previous inconsistent results when testing the TSR on unicellular organisms, and shows that when a single-growth stage is considered the predicted negative response to temperature is revealed.Versión del edito

Cooperative and Escaping Mechanisms between Circulating Tumor Cells and Blood Constituents

Metastasis is the leading cause of cancer-related deaths and despite measurable progress in the field, underlying mechanisms are still not fully understood. Circulating tumor cells (CTCs) disseminate within the bloodstream, where most of them die due to the attack of the immune system. On the other hand, recent evidence shows active interactions between CTCs and platelets, myeloid cells, macrophages, neutrophils, and other hematopoietic cells that secrete immunosuppressive cytokines, which aid CTCs to evade the immune system and enable metastasis. Platelets, for instance, regulate inflammation, recruit neutrophils, and cause fibrin clots, which may protect CTCs from the attack of Natural Killer cells or macrophages and facilitate extravasation. Recently, a correlation between the commensal microbiota and the inflammatory/immune tone of the organism has been stablished. Thus, the microbiota may affect the development of cancer-promoting conditions. Furthermore, CTCs may suffer phenotypic changes, as those caused by the epithelial–mesenchymal transition, that also contribute to the immune escape and resistance to immunotherapy. In this review,we discuss the findings regarding the collaborative biological events among CTCs, immune cells, and microbiome associated to immune escape and metastatic progression

Pre-Treatment of Fish By-Products to Optimize Feeding of Tenebrio molitor L. Larvae

Fish discards are organic waste with high and good-quality protein levels, as well as a fatty acid profile rich in n−3 LCPUFAs, mainly eicosapentaenoic acid and docosahexaenoic acid. These discards can be used as food for Tenebrio molitor (Linnaeus, 1758) larvae, thus increasing the nutritional value of this insect. This study focused on increasing larval acceptance of fish through different pre-treatments of the diets provided, as well as increasing the accumulation of EPA and DHA in fish-fed larvae. Four different diets were prepared: control (broiler feed), DGF50: 50% dried ground fish (Pagellus bogaraveo, Brünnich, 1768) + 50% broiler feed, for different periods, FGF100: 100% fresh ground P. bogaraveo and DUF100: 100% dried whole unground P. bogaraveo. Growth, mortality, proximate composition, fatty acid profile and lipid nutritional indices were determined. Larvae fed with FGF100 displayed better results among treatments, doubling the initial weight, as well as increasing their protein level and decreasing fat levels. Regarding fatty acids, eicosapentaenoic acid and docosahexaenoic acid were only detected in larvae fed with a fish-based diet for a period longer than 5 days. These results show that pre-treatment of fish-based diets causes changes in the growth and compositional parameters of T. molitor larvae

Study of maternal nutrition and genetic on the foetal adiposity programming (The PREOBE Study)

Introducción: La genética y la alimentación de la madre antes y durante el embarazo, las distintas patologías metabólicas maternas, así como la ingesta de nutrientes en los primeros meses de vida del recién nacido parecen estar implicados en la etiología de la obesidad y sus consecuencias a largo plazo. La posible contribución de estos y otros factores, los mecanismos y sus efectos en el metabolismo y desarrollo de la enfermedad están aún en fase de investigación. Objetivo: Obtener un mayor conocimiento del desarrollo del tejido adiposo fetal y la influencia de factores genéticos, dietéticos y ambientales sobre el riesgo a largo plazo de padecer obesidad. Metodología: Se han establecido cuatro grupos de estudio de 30 madres gestantes cada uno: 1) grupo control; 2) madres con intolerancia a la glucosa/diabetes gestacional; 3) madres con escasa ganancia ponderal durante el embarazo, y 4) madres con sobrepeso/obesidad al inicio del embarazo. Se realizará un análisis de los siguientes parámetros: 1) ingesta dietética; 2) hábitos y estilo de vida; 3) actividad física; 4) antropometría y composición corporal; 5) estudio hematológico; 6) estudio bioquímico (biomarcadores lipídicos y metabólicos); 7) perfil inmunológico; 8) perfil psicológico; 9) marcadores genéticos, y 10) marcadores microbiológicos; todos ellos relacionados con la formación del tejido adiposo fetal en las primeras etapas de la vida y el riesgo de padecer obesidad en el futuro. Conclusión: En este proyecto, coordinado por el Departamento de Pediatría de la Facultad de Medicina de asegula Universidad de Granada y que cuenta con la participación de otros grupos de investigación de larga y acreditada experiencia, se pretende obtener un mayor conocimiento de los orígenes de la obesidad en la infancia y posterior desarrollo de esta enfermedad en etapas posteriores de la vida.Background: Maternal genetics and feeding before and during pregnancy, different maternal metabolic pathologies, as well as nutrient intakes of newborns in their first months of life may be involved in the obesity aetiology and its long-term consequences. The possible role of these and others factors, the mechanisms and the effects on the metabolism, and the development of this disease need further research. Objective: To acquire more knowledge about foetal adipose tissue development and the influence of genetic, dietetic and environmental factors on the risk to suffer from obesity. Methodology: Four study groups have been established with 30 pregnant women in each one: 1) control group; 2) mothers with glucose intolerance/gestational diabetes; 3) women with low weight gain during pregnancy, and 4) women with overweight/obesity at the beginning of the pregnancy. The magnitudes to be studied are: 1) dietary intake; 2) life-style habits; 3) physical activity; 4) anthropometry and body composition; 5) haematological study; 6) biochemical study (lipid and metabolic biomarkers); 7) immune function profile related to nutritional status; 8) psychological profile; 9) genetic biomarkers, and 10) microbiological markers; all of them in relation to the development of the foetal adipose tissue in the first stages of life and the risk of suffering from obesity in the future. Conclusion: This project, coordinated by the Department of Paediatrics of the School of Medicine in the University of Granada, and with the collaboration of well-known and expert research groups, tries to contribute to the knowledge about the obesity aetiology in infancy and its subsequent development in later periods of life.El proyecto PREOBE está financiado por la Consejería de Innovación, Ciencia y Empresa de la Junta de Andalucía (Proyecto de Excelencia n.º P06-CTS-02341)