Péptidos implicados en la regulación de la homeostasis de la energía e inflamación crónica de bajo grado en edad pediátrica

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Pediatría. Fecha de Lectura: 25-06-2021Dentro del origen multifactorial de la obesidad, la regulación de la homeostasis de la energía constituye un factor clave en su desarrollo. Así, el hipotálamo desempeña un papel fundamental en el control del equilibrio energético, respondiendo tanto a señales centrales como periféricas que informan sobre el estado energético, modulando la ingesta de alimentos, el gasto energético y el metabolismo de los hidratos de carbonos y de los lípidos. La obesidad se caracteriza por una acumulación excesiva de tejido adiposo que provoca una alteración de sus funciones endocrinas y un estado de inflamación crónica de bajo grado que desencadena el desarrollo de comorbilidades como el síndrome metabólico. En nuestro estudio, en edad pediátrica, hemos profundizado el papel de leptina e insulina como señales de adiposidad implicadas en la regulación de la ingesta dietética y de nesfatina-1 y adropina como “nuevas señales” que podrían estar implicadas en la homeostasis de la energía. Además, hemos ahondado en el estudio de la proteína C-reactiva (PCR) como marcador de inflamación crónica, investigando factores reguladores de sus niveles plasmáticos, y su probable implicación en la etiopatogenia de alteraciones metabólicas. Nuestros resultados han demostrado una acción anorexigénica de leptina dependiente de los valores sanguíneos de insulina en niñas. También hemos evidenciado una relación de la obesidad tanto con los niveles de nesfatina-1 como con los de adropina, presentando ambos péptidos una diferente regulación dependiente del sexo. La asociación observada de leptina con nesfatina-1 y adropina sugiere la posible regulación de la secreción de estos péptidos a nivel central por la leptina. Con referencia a la PCR como marcador de inflamación crónica y de alteraciones metabólicas, hemos confirmado que el tejido adiposo es una fuente extrahepática de PCR, cuya expresión estaría asociada potencialmente con la gravedad de la inflamación. Al analizar la validez de PCR como marcador de síndrome metabólico, hemos constatado su utilidad como biomarcador en niñas adolescentes, pero no en niños, en los que su asociación parece estar influenciada por leptina. Siguiendo esta línea, en esta misma población, hemos observado que la leptina también participaría como mediador de la acción inflamatoria de la testosterona en los niños adolescentes. Por último, hemos demostrado que, a diferencia de otros antioxidantes liposolubles, los niveles de retinol plasmático se asocian negativamente de manera significativa con las concentraciones de PCR. En conclusión, nuestros datos corroboran la existencia de un importante dimorfismo sexual en la fisiopatología de la obesidad que ha de tenerse en cuenta ya en la edad pediátrica.Trabajo realizado gracias a una Beca de la Fundación Conchita Rábago y a la financiación del Instituto de Salud Carlos III a través de los proyectos FIS 14/00344 y 18/01016

Pasta de tomate de árbol

En la cartilla se enseña la forma corriente de elaborar la Pasta de Tomate de árbol (bocadillo), así como materiales, métodos e ingredientes del procesoThe primer shows the usual way to make the Tomato Tree Pasta (sandwich), as well as materials, methods and ingredients of the processIntroducción – Objetivo general – Proceso – Determinar costo de producción – Higiene y segurida

Sex-dependent relationship of C-reactive protein levels with HDL-cholesterol and HDL-phospholipid concentrations in children

Obesity has been consistently associated with inflammation but the influence of HDL on this association remains under study. Our study analyzes the influence of obesity-related parameters in the relationship of high-sensitivity C-reactive protein (hs-CRP) with HDL-cholesterol and HDL-phospholipid in male and female adolescents. The study sample population comprised 350 males and 401 females aged 12 to 16 years. Information regarding anthropometric parameters, HDL-cholesterol, HDL-phospholipid, adiponectin, leptin, insulin, and hs-CRP concentrations was available. hs-CRP levels were inversely related to HDL-cholesterol and HDL-phospholipid in males but not in females, and were positively related to leptin concentrations in both sexes but were not related to adiponectin levels. In regression analyses, HDL-phospholipid and leptin appeared significantly associated to hs-CRP in males in a model explaining 14.3% of hs-CRP variation. In females, only leptin appeared related to hs-CRP concentrations. After adjusting by leptin and adiponectin, males in the highest hs-CRP tertile showed significantly lower levels of HDL-cholesterol and HDL-phospholipid than those in tertiles 1 and 2, while no significant differences in HDL-cholesterol and HDL-phospholipid concentrations by hs-CRP tertile were observed in females. In summary, high hs-CRP levels were associated with lower plasma HDL-cholesterol and HDL-phospholipid concentrations in male adolescents irrespective of adipokines, while in females, HDL-related parameters are not associated with hs-CRP concentrationsTis research was funded by the Fondo de Investigación Sanitaria, Grant Number PI 18/01016, and by Biobank Grant Number FEDERRD09/0076/00101. Claudia Vales-Villamarín is recipient of a research contract from Carlos III Institute of Health (pFIS).Te article is dedicated to the late Prof. Manuel de Oya as the warmest homage to his memor

Advanced immunotherapies for glioblastoma: tumor neoantigen vaccines in combination with immunomodulators

Correction to: Advanced immunotherapies for glioblastoma: tumor neoantigen vaccines in combination with immunomodulators. Acta Neuropathol Commun. 2023 Jul 12;11(1):116. doi: 10.1186/s40478-023-01600-2. PMID: 37438824.Glial-origin brain tumors, including glioblastomas (GBM), have one of the worst prognoses due to their rapid and fatal progression. From an oncological point of view, advances in complete surgical resection fail to eliminate the entire tumor and the remaining cells allow a rapid recurrence, which does not respond to traditional therapeutic treatments. Here, we have reviewed new immunotherapy strategies in association with the knowledge of the immune micro-environment. To understand the best lines for the future, we address the advances in the design of neoantigen vaccines and possible new immune modulators. Recently, the efficacy and availability of vaccine development with different formulations, especially liposome plus mRNA vaccines, has been observed. We believe that the application of new strategies used with mRNA vaccines in combination with personalized medicine (guided by different omic's strategies) could give good results in glioma therapy. In addition, a large part of the possible advances in new immunotherapy strategies focused on GBM may be key improving current therapies of immune checkpoint inhibitors (ICI), given the fact that this type of tumor has been highly refractory to ICI.This study has been funded by Instituto de Salud Carlos III (ISCIII) through the project “CP21/00116 and PI22/0117” and co-funded by the European Union to RG, by “Asociación Española contra el Cancer (AECC) grant: INVES192GARG to RG and by Ministerio de Ciencia e Innovación and FEDER funds: PI21/01406 to JMSS.S

Children with type 1 diabetes have elevated high-sensitivity C-reactive protein compared with a control group

Introduction Our objective was to compare high-sensitivity C-reactive protein (hsCRP) levels in children with type 1 diabetes, healthy controls, and children with obesity. Additionally, we aimed to analyze the association between hsCRP levels and glycemic control measured by glycohemoglobin A (HbA1c) and anthropometric and biochemical variables. Research design and methods We conducted a non-randomized descriptive study of children with type 1 diabetes matched for sex and age with a control group and group with obesity. We recorded anthropometric parameters and studied variables related to diabetes, blood pressure, lipid profile, and HbA1c. hsCRP was measured by ELISA. Results We included 49 children with type 1 diabetes, 46 controls, and 40 children with obesity. hsCRP levels were significantly higher in the group with type 1 diabetes compared with controls and nearly significantly lower than in the group comprising children with obesity. We found no correlation between hsCRP and HbA1c and characteristics of type 1 diabetes with the exception of albumin to creatinine ratio. Statistically significant association was found between hsCRP and body mass index (BMI) and waist circumference Z-score. Conclusions The higher hsCRP levels observed in children with type 1 diabetes compared with a control group with a similar BMI suggest a basal inflammatory state that could increase cardiovascular risk. The main factors related to hsCRP are BMI and waist circumference, so obesity prevention should be a priority when performing follow-up in children with type 1 diabetes.This work was supported by Fundación Familia Alons

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

Elaboración de pastas, bocadillos y jaleas

Se compilan las cartillas 1 a la 3 de la serie “Agroindustria: elaboración de pastas, bocadillos y jaleas” en la que se presentan de forma interactiva los materiales, métodos e ingredientes para preparación de pasta de Tomate, pasta de tomate de árbol (bocadillo) y bocadillo a base de papaya.Booklets 1 to 3 of the series "Agribusiness: elaboration of pastas, sandwiches and jellies" are compiled in which the materials, methods and ingredients for preparation of tomato paste, tree tomato paste (sandwich) are presented interactively ) and papaya-based sandwich.Volumen 1. Pasta de tomate -- Volumen 2. Pasta de tomate de árbol -- Volumen 3. Bocadillo de papayaCréditos versión digital: escaneo y organización de textos Regional Caldas, Luz Marelby Giraldo, José Julián Escobar, Cindy Nayely Taborda; Equipo de Gestión del Sistema de Bibliotecas, Martha Luz Gutiérrez Ortega, Adriana Rincón Avendaño; versión digital, Alberto Mario Angulo Flórez, Ekatherine Cardona, Angie Tatiana Lozano Calderón, Karime Andrea Montañez Pinzón, Camilo Jáuregui BecerraMicrositio creado en el año 2013

Sex-Dependent Mediation of Leptin in the Association of Perilipin Polymorphisms with BMI and Plasma Lipid Levels in Children

Variations in the perilipin (PLIN) gene have been suggested to be associated with obesity and its related alterations, but a different nutritional status seems to contribute to differences in these associations. In our study, we examined the association of several polymorphisms at the PLIN locus with obesity and lipid profile in children, and then analyzed the mediation of plasma leptin levels on these associations. The single-nucleotide polymorphisms (SNPs) rs894160, rs1052700, and rs2304795 in PLIN1, and rs35568725 in PLIN2, were analyzed by RT-PCR in 1264 children aged 6&ndash;8 years. Our results showed a contrasting association of PLIN1 rs1052700 with apolipoprotein (Apo) A-I levels in boys and girls, with genotype TT carriers showing significantly higher Apo A-I levels in boys and significantly lower Apo A-I levels in girls. Significant associations of the SNP PLIN2 rs35568725 with high-density lipoprotein cholesterol (HDL-cholesterol), Apo A-I, and non-esterified fatty acids (NEFA) were observed in boys but not in girls. The associations of the SNPs studied with body mass index (BMI), NEFA, and Apo A-I in boys and girls were different depending on leptin concentration. In conclusion, we describe the mediation of plasma leptin levels in the association of SNPs in PLIN1 and PLIN2 with BMI, Apo A-I, and NEFA. Different leptin levels by sex may contribute to explain the sex-dependent association of the PLIN SNPs with these variables

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

Promoting Physical Activity in a Primary Care Practice in People Living with Dementia and Their Family Caregivers

People living with dementia (PLWD) and their family caregivers report higher rates of having a sedentary lifestyle than their non-disabled peers do. This study analyzed the effectiveness of an intervention designed to increase physical activity among PLWD and their family caregivers in primary health care settings. A cluster-randomized multicenter clinical trial was conducted. Participants from four health centers were randomly assigned to the intervention group (IG) or the control group (CG) in a 1:1 ratio using Epidat software. After a seven-day period with a digital pedometer (Omron Hj-321 lay-UPS), participants were asked to complete the International Physical Activity Questionnaire Short Form (IPAQ-SF). PLWD and caregivers allocated to the IG were given brief advice, educational materials and an additional 15 min appointment to prescribe an individualized physical activity plan. Seventy PLWD and 80 caregivers were assigned to the CG and 70 PLWD and 96 caregivers were assigned to the IG. Results of the pedometer assessment show that in PLWD, the IG’s activity increased by 52.89 aerobic steps at 6 months and the CG’s activity decreased by 615.93 aerobic steps, showing a net increase in the IG of 668.82 (95% CI: −444.27 to 1781.91; p = 0.227). For caregivers in the IG, activity increased by 356.91 aerobic steps and in the CG it decreased by 12.95 aerobic steps, showing a net increase in favor of the IG of 369.86 (95%CI: −659.33 to 1399.05; p = 0.476). The effectiveness of interventions to increase physical activity in this group of people with dementia and their caregivers did not achieved positive results overall but may have provided suggestions for family physicians and physical therapists to improve physical activity among people with dementia and their families