Exosomal Osteoclast-Derived miRNA in Rheumatoid Arthritis: From Their Pathogenesis in Bone Erosion to New Therapeutic Approaches.

Rheumatoid arthritis (RA) is an autoimmune disease that causes inflammation, pain, and ultimately, bone erosion of the joints. The causes of this disease are multifactorial, including genetic factors, such as the presence of the human leukocyte antigen (HLA)-DRB1*04 variant, alterations in the microbiota, or immune factors including increased cytotoxic T lymphocytes (CTLs), neutrophils, or elevated M1 macrophages which, taken together, produce high levels of pro-inflammatory cytokines. In this review, we focused on the function exerted by osteoclasts on osteoblasts and other osteoclasts by means of the release of exosomal microRNAs (miRNAs). Based on a thorough revision, we classified these molecules into three categories according to their function: osteoclast inhibitors (miR-23a, miR-29b, and miR-214), osteoblast inhibitors (miR-22-3p, miR-26a, miR-27a, miR-29a, miR-125b, and miR-146a), and osteoblast enhancers (miR-20a, miR-34a, miR-96, miR-106a, miR-142, miR-199a, miR-324, and miR-486b). Finally, we analyzed potential therapeutic targets of these exosomal miRNAs, such as the use of antagomiRs, blockmiRs, agomiRs and competitive endogenous RNAs (ceRNAs), which are already being tested in murine and ex vivo models of RA. These strategies might have an important role in reestablishing the regulation of osteoclast and osteoblast differentiation making progress in the development of personalized medicine.

[Analysis of BRAF and NRAS mutations in thyroid tumors in patients from Argentina]. / Análisis de mutaciones BRAF y NRAS de tumores tiroideos en pacientes de Argentina.

INTRODUCTION: Molecular alterations in follicular cells in the BRAF or NRAS genes have been reported to be associated with the process of carcinogenesis. Our aim was to determine the mutational frequency of BRAF and NRAS in fine-needle aspiration (FNA) specimens in our population. METHODS: The mutational status of BRAF (codon 600) and NRAS (codon 61) was analysed by qPCR in 193 FNA specimens from suspicious nodules and compared with pathological data of 115 patients. RESULTS: BRAF mutation was identified in 40 samples (74.1%) of FNAs classified as Bethesda VI (n = 54). In samples histologically diagnosed as classic papillary thyroid carcinoma (cPTC, n = 47), mutation was observed in 70% of cases, while in other subtypes the prevalence was lower (p = 0.013). In FNA specimens of follicular lesions (n = 36), positivity for NRAS was found in 50% of the follicular carcinomas (FTCs), but only in 6.7% of adenomas. Finally, there was a significant correlation between BRAF and PTC with lymph-node metastasis (p = 0.014) and increased relative risk of recurrence based on the Argentine Intersociety Consensus (RR = 6.77, p = 0.022). No significant differences were found between BRAF mutation and other features of aggressiveness in PTC. CONCLUSION: BRAF and NRAS mutations are observed in a significant number of PTCs and FTCs, in our population. There is a significant correlation between BRAF mutation and lymph-node metastasis.

Introducción: Se ha descrito que alteraciones moleculares de las células foliculares tiroideas en el gen BRAF o en NRAS están asociadas con el proceso de carcinogénesis. Nuestro objetivo fue conocer la frecuencia mutacional de BRAF y NRAS a partir de muestras de punción aspirativa con aguja fina (PAAF) en nuestra población. Métodos: Se analizó por qPCR el estado mutacional de BRAF (codón 600) y NRAS (codón 61) de 193 muestras obtenidas por PAAF de nódulos sospechosos y se comparó con los datos de la anatomía patológica de 115 pacientes. Resultados: La mutación BRAF se identificó en 40 muestras (74.1%) de las punciones categorizadas como Bethesda VI (n = 54). En las muestras que se correspondieron con carcinoma papilar de tiroides (CPT) variante clásica por histología (n = 47), el 70% presentó la mutación, mientras que en los otros subtipos la prevalencia fue más baja (p = 0.013). En muestras de lesión folicular (n = 36), el 50% de los carcinomas foliculares resultaron positivos para NRAS pero solo el 6.7% de los adenomas presentaron esta variación. La presencia de mutación BRAF y CPT se asociaron con metástasis en los ganglios linfáticos (p = 0.014) y mayor riesgo relativo de recurrencia según el Consenso Argentino Intersocietario (RR = 6.77, p = 0.022). No hubo diferencias significativas entre la mutación de BRAF y otras características de agresividad en CPT. Conclusión: La mutación de BRAF y NRAS se observa en un número significativo de CPT y carcinoma folicular, respectivamente, en nuestra población. La mutación BRAF se correlaciona significativamente con metástasis en los ganglios linfáticos.

Analysis of Novel Immunological Biomarkers Related to Rheumatoid Arthritis Disease Severity.

Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs) are the most frequently used rheumatoid arthritis (RA) diagnostic markers, but they are unable to anticipate the patient's evolution or response to treatment. The aim of this study was to identify possible severity biomarkers to predict an upcoming flare-up or remission period. To address this objective, sera and anticoagulated blood samples were collected from healthy controls (HCs; n = 39) and from early RA (n = 10), flare-up (n = 5), and remission (n = 16) patients. We analyzed leukocyte phenotype markers, regulatory T cells, cell proliferation, and cytokine profiles. Flare-up patients showed increased percentages of cluster of differentiation (CD)3+CD4- lymphocytes (p < 0.01) and granulocytes (p < 0.05) but a decreased natural killer (NK)/T lymphocyte ratio (p < 0.05). Analysis of leukocyte markers by principal component analysis (PCA) and receiver operating characteristic (ROC) curves showed that CD45RO+ (p < 0.0001) and CD45RA+ (p < 0.0001) B lymphocyte expression can discriminate between HCs and early RA patients, while CD3+CD4- lymphocyte percentage (p < 0.0424) and CD45RA+ (p < 0.0424), CD62L+ (p < 0.0284), and CD11a+ (p < 0.0185) B lymphocyte expression can differentiate between flare-up and RA remission subjects. Thus, the combined study of these leukocyte surface markers could have potential as disease severity biomarkers for RA, whose fluctuations could be related to the development of the characteristic pro-inflammatory environment.

Análisis de mutaciones BRAF y NRAS de tumores tiroideos en pacientes de Argentina / Analysis of BRAF and NRAS mutations in thyroid tumors in patients from Argentina

Resumen Introducción : Se ha descrito que alteraciones molecu lares de las células foliculares tiroideas en el gen BRAF o en NRAS están asociadas con el proceso de carcinogé nesis. Nuestro objetivo fue conocer la frecuencia muta cional de BRAF y NRAS a partir de muestras de punción aspirativa con aguja fina (PAAF) en nuestra población. Métodos : Se analizó por qPCR el estado mutacional de BRAF (codón 600) y NRAS (codón 61) de 193 mues tras obtenidas por PAAF de nódulos sospechosos y se comparó con los datos de la anatomía patológica de 115 pacientes. Resultados : La mutación BRAF se identificó en 40 muestras (74.1%) de las punciones categorizadas como Bethesda VI (n = 54). En las muestras que se correspon dieron con carcinoma papilar de tiroides (CPT) variante clásica por histología (n = 47), el 70% presentó la muta ción, mientras que en los otros subtipos la prevalencia fue más baja (p = 0.013). En muestras de lesión folicular (n = 36), el 50% de los carcinomas foliculares resultaron positivos para NRAS pero solo el 6.7% de los adenomas presentaron esta variación. La presencia de mutación BRAF y CPT se asociaron con metástasis en los gan glios linfáticos (p = 0.014) y mayor riesgo relativo de recurrencia según el Consenso Argentino Intersocietario (RR = 6.77, p = 0.022). No hubo diferencias significativas entre la mutación de BRAF y otras características de agresividad en CPT. Conclusión : La mutación de BRAF y NRAS se observa en un número significativo de CPT y carcinoma folicular, respectivamente, en nuestra población. La mutación BRAF se correlaciona significativamente con metástasis en los ganglios linfáticos.

Abstract Introduction : Molecular alterations in follicular cells in the BRAF or NRAS genes have been reported to be associated with the process of carcinogenesis. Our aim was to determine the mutational frequency of BRAF and NRAS in fine-needle aspiration (FNA) specimens in our population. Methods : The mutational status of BRAF (codon 600) and NRAS (codon 61) was analysed by qPCR in 193 FNA specimens from suspicious nodules and compared with pathological data of 115 patients. Results : BRAF mutation was identified in 40 samples (74.1%) of FNAs classified as Bethesda VI (n = 54). In samples histologically diagnosed as classic papillary thyroid carcinoma (cPTC, n = 47), mutation was observed in 70% of cases, while in other subtypes the prevalence was lower (p = 0.013). In FNA specimens of follicular lesions (n = 36), positivity for NRAS was found in 50% of the follicular carcinomas (FTCs), but only in 6.7% of adenomas. Finally, there was a significant correlation between BRAF and PTC with lymph-node metastasis (p = 0.014) and increased relative risk of recurrence based on the Argentine Intersociety Consensus (RR = 6.77, p = 0.022). No significant differences were found between BRAF mutation and other features of aggressiveness in PTC. Conclusion : BRAF and NRAS mutations are observed in a significant number of PTCs and FTCs, in our popu lation. There is a significant correlation between BRAF mutation and lymph-node metastasis.

Beneficial Effects of Olive Oil Enriched with Lycopene on the Plasma Antioxidant and Anti-Inflammatory Profile of Hypercholesterolemic Patients.

Olive oil and lycopene are foods that have potent antioxidant activity. The objective was to determine the effects of consumption of olive oil enriched with lycopene on oxidative stress biomarkers in hypercholesterolemic subjects. We examined the effects of oil enriched with lycopene extract daily intake during 1 month on plasma antioxidant capacity, lipids profile (triacylgycerols, total cholesterol, cHDL; cLDL, ox-LDL), biomarkers of oxidative stress, and inflammatory markers related with atherosclerosis risk (C-reactive protein (CRP), IL-6; sDC4L) in subjects hypercholesteremics (cholesterol > 220 mg/dL). In the group consuming olive oil-lycopene, significant increases (p < 0.05) in the levels of plasma lycopene concentration (0.146 ± 0.03 versus 0.202 ± 0.04 (µmol/L)), α-carotene (0.166 ± 0.064 versus 0.238 ± 0.07) and in ß-carotene (0.493 ± 0.187 versus 0.713 ± 0.221) were observed. These results are linked with the increases of plasma antioxidants and decreases biomarkers of oxidative stress (carbonyl groups, malondialdehyde and 8-hydroxy-deoxiguanosine) observed in hypercholesterolemic group. In relation to lipid profile, a significant decrease was observed in the levels of ox-LDL (781 ± 302 versus 494 ± 200), remaining unchanged the levels of TG, cholesterol, HDL and LDL-c. Regarding inflammatory biomarkers, the levels of CRP and IL-6 decreased significantly. The positive results obtained in this study support the use of olive oil enriched with lycopene to reduce the risk of coronary disease.

Gamificación educativa en el laboratorio de biología celular / Educational gamification in the cell biology laboratory

La incorporación de estrategias de gamificación en la docencia se ha descrito como una herramienta para aumentar la motivación y el compromiso de los alumnos con la materia. Bajo esta premisa, se ha desarrollado una experiencia de innovación educativa mediante la plataforma Kahoot! en la primera y última práctica de laboratorio de la asignatura de Biología Celular del Grado en Biología. Los participantes fueron 135 alumnos repartidos en 12 grupos de laboratorio, que se dividieron entre experimentales y controles. Todos los grupos resolvieron un cuestionario en papel acerca de los conceptos explicados en clase, al finalizar ambas prácticas (post-test), pero sólo aquellos grupos experimentales resolvían un cuestionario antes de la clase (pre-test). Antes de la primera práctica, los alumnos de los grupos experimentales respondieron al pre-test mediante el Kahoot! Sin embargo, para la última práctica algunos grupos lo resolvieron jugando al Kahoot! y otros, con papel y bolígrafo. Los resultados mostraron que aquellos alumnos que fueron seleccionados para jugar a Kahoot!, obtuvieron un mayor número de aciertos en el test realizado tras la sesión práctica (post-test) con respecto a aquellos que no resolvieron ningún pre-test o, que lo hicieron de un modo clásico. Por lo tanto, nuestros resultados sugieren que implementar la jugabilidad en la docencia incrementa considerablemente la motivación del alumnado debido, probablemente, a cambios fisiológicos experimentados por el cerebro durante el juego y a la creación de un clima positivo, que facilitan el proceso de aprendizaje.

SUMMARY: The incorporation of gamification strategies in teaching has been described as a tool to increase the motivation and engagement of students with the subject. Under this premise, an educational innovation experience has been developed using the Kahoot! platform in the first and last laboratory practice of the Cell Biology course of the Biology degree. The participants were 135 students divided into 12 laboratory groups, which were divided into experimental and control groups. All groups solved a questionnaire on paper about the concepts explained in class, at the end of both practices (post-test), but only the experimental groups solved a questionnaire before the class (pre-test). Before the first practice, students in the experimental groups answered the pre-test using Kahoot! However, for the last practice, some groups solved it by playing Kahoot! and others with pen and paper. The results showed that those students who were selected to play Kahoot! obtained a higher number of correct answers in the test performed after the practical session (post-test) than those who did not solve any pre- test or who did it in a classical way. Therefore, our results suggest that implementing gamification in teaching considerably increases student motivation, probably due to physiological changes experienced by the brain during the game and the creation of a positive climate, which facilitates the learning process.

Giant Cell Tumor of the Carotid Body: A Rare Tumor with Malignant Potential.

Introduction: Carotid body tumors (CBTs) are certainly unusual. They are vascular lesions originating from paraganglionic cells, located at the common carotid artery (CCA) bifurcation. They represent less than 0.5% of head and neck tumors, approximately 1-3 cases per million. Malignant CBTs are extremely rare; in the literature, published rates on average are < 10%. The diagnostic criteria for malignancy should be based on the finding of distant metastasis. Due to its unpredictable nature and its malignant potential, diagnosis before metastasis and complete surgical resection are the keys to a favorable prognosis. Case Report: Given little experience in CBTs, its biology and treatment remain uncertain. We present the case of a 48-years-old patient, with a mass on the left side of the neck that was found to be a vast CBT with suspicious histopathology. Its size, rare location, pathologic findings, and management strategy applied for its treatment, illustrate an unusual case that highlights the importance of its publication. Conclusions: CBT is rare, but subject to cure lesion if resected without metastatic or residual disease. This is why surgery should be performed whenever possible and why it is so necessary to study this pathology thoroughly and to take it into account in the differential diagnosis.

Non-invasive follicular neoplasm with papillary-like nuclear features: a challenging and infrequent entity in Argentina.

PURPOSE: Non-invasive encapsulated follicular variant of papillary thyroid cancer was reclassified as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). These neoplasms have an extremely low malignant potential. The aim of this study was (1) to assess the prevalence of NIFTP in patients with papillary thyroid carcinoma, (2) to evaluate their outcomes, and (3) to determine their molecular profile. METHODS: Multicenter, descriptive, retrospective study. Patients with papillary thyroid cancer diagnosed from January 2006 to December 2016 from 11 referral centers were included. Diagnosis of NIFTP was based on criteria described by Nikiforov et al. in 2018. At least two pathologists agreed on the diagnosis. Two thousand six hundred and seventy-seven papillary thyroid cancer patients were included; 456 (17%) of them were follicular variant papillary thyroid cancer, and 30 (1.12%) fulfilled diagnostic criteria for NIFTP. RESULTS: Each of the 30 included patients underwent a total thyroidectomy, and 50% were treated with radioiodine (median dose 100 mCi). After a median follow-up of 37 months, 84% of patients had an excellent response, 3% had an indeterminate response and data was missing in the remaining 13%. No metastatic lymph nodes, distant metastases or recurrences were found. RAS mutations were detected in 4 patients (13%). CONCLUSION: The prevalence of NIFTP in our series is amongst the lowest reported. Excellent outcomes of patients underscore their low malignant potential. Molecular findings differ from other series, probably related to environmental or ethnic features of our population and the meticulous criteria for diagnosing NIFTP.

Individuals With SARS-CoV-2 Infection During the First and Second Waves in Catalonia, Spain: Retrospective Observational Study Using Daily Updated Data.

BACKGROUND: A description of individuals with SARS-CoV-2 infection comparing the first and second waves could help adapt health services to manage this highly transmissible infection. OBJECTIVE: We aimed to describe the epidemiology of individuals with suspected SARS-CoV-2 infection, and the characteristics of patients with a positive test comparing the first and second waves in Catalonia, Spain. METHODS: This study had 2 stages. First, we analyzed daily updated data on SARS-CoV-2 infection in individuals from Girona (Catalonia). Second, we compared 2 retrospective cohorts of patients with a positive reverse-transcription polymerase chain reaction or rapid antigen test for SARS-CoV-2. The severity of patients with a positive test was defined by their admission to hospital, admission to intermediate respiratory care, admission to the intensive care unit, or death. The first wave was from March 1, 2020, to June 24, 2020, and the second wave was from June 25, 2020, to December 8, 2020. RESULTS: The numbers of tests and cases were lower in the first wave than in the second wave (26,096 tests and 3140 cases in the first wave versus 140,332 tests and 11,800 cases in the second wave), but the percentage of positive results was higher in the first wave than in the second wave (12.0% versus 8.4%). Among individuals with a positive diagnostic test, 818 needed hospitalization in the first wave and 680 in the second; however, the percentage of hospitalized individuals was higher in the first wave than in the second wave (26.1% versus 5.8%). The group that was not admitted to hospital included older people and those with a higher percentage of comorbidities in the first wave, whereas the characteristics of the groups admitted to hospital were more alike. CONCLUSIONS: Screening systems for SARS-CoV-2 infection were scarce during the first wave, but were more adequate during the second wave, reflecting the usefulness of surveillance systems to detect a high number of asymptomatic infected individuals and their contacts, to help control this pandemic. The characteristics of individuals with SARS-CoV-2 infection in the first and second waves differed substantially; individuals in the first wave were older and had a worse health condition.

Histidine-Rich Glycoprotein Inhibits HIV-1 Infection in a pH-Dependent Manner.

Histidine-rich glycoprotein (HRG) is an abundant plasma protein with a multidomain structure, allowing its interaction with many ligands, including phospholipids, plasminogen, fibrinogen, IgG antibodies, and heparan sulfate. HRG has been shown to regulate different biological responses, such as angiogenesis, coagulation, and fibrinolysis. Here, we found that HRG almost completely abrogated the infection of Ghost cells, Jurkat cells, CD4+ T cells, and macrophages by HIV-1 at a low pH (range, 6.5 to 5.5) but not at a neutral pH. HRG was shown to interact with the heparan sulfate expressed by target cells, inhibiting an early postbinding step associated with HIV-1 infection. More importantly, by acting on the viral particle itself, HRG induced a deleterious effect, which reduces viral infectivity. Because cervicovaginal secretions in healthy women show low pH values, even after semen deposition, our observations suggest that HRG might represent a constitutive defense mechanism in the vaginal mucosa. Of note, low pH also enabled HRG to inhibit the infection of HEp-2 cells and Vero cells by respiratory syncytial virus (RSV) and herpes simplex virus 2 (HSV-2), respectively, suggesting that HRG might display broad antiviral activity under acidic conditions.IMPORTANCE Vaginal intercourse represents a high-risk route for HIV-1 transmission. The efficiency of male-to-female HIV-1 transmission has been estimated to be 1 in every 1,000 episodes of sexual intercourse, reflecting the high degree of protection conferred by the genital mucosa. However, the contribution of different host factors to the protection against HIV-1 at mucosal surfaces remains poorly defined. Here, we report for the first time that acidic values of pH enable the plasma protein histidine-rich glycoprotein (HRG) to strongly inhibit HIV-1 infection. Because cervicovaginal secretions usually show low pH values, our observations suggest that HRG might represent a constitutive antiviral mechanism in the vaginal mucosa. Interestingly, infection by other viruses, such as respiratory syncytial virus and herpes simplex virus 2, was also markedly inhibited by HRG at low pH values, suggesting that extracellular acidosis enables HRG to display broad antiviral activity.

Role of the Mechanisms of Detection in the Increased Risk of Thyroid Cancer: A Retrospective Cohort Study in an HMO in Buenos Aires.

BACKGROUND: Two hypotheses attempt to explain the increase of thyroid cancer (TC) incidence: overdetection by excessive diagnostic scrutiny and a true increase in new cases brought about by environmental factors. Changes in the mechanism of detection and the risk of incidentally diagnosed TC could result in an increase of TC incidence. METHODS: Retrospective cohort study. We identified incident cases of TC from the pathological reports of patients in a HMO and review of clinical records. The results were analyzed in two periods: 2003-2007 and 2008-2012. Incidence rates expressed per 100,000 person-years (with 95% CI) and relative risk of incidence rates of incidental and nonincidental TC were estimated. RESULTS: The relative risk of incidentally detecting a thyroid cancer in 2008-2012 compared to 2003-2007 was 6.06 (95%CI 1.84-20.04). Clinical evaluations detected 31 (75.6%) cancers in the period 2003-2007 and 70 (51.8%) cancers in the period 2008-2012 (p<0.007). Although tumor median size was significantly lower in the period 2008-2012 (10 vs. 14 mm, p<0.03), tumors greater than 40 mm (4.3%) were only present in 2008-2012. The female/male ratio decreased between analyzed periods from 8 (3-21) to 4 (3-7). CONCLUSIONS: Our findings partially support the hypothesis of increased incidence due to overdetection but do not explain the changes in the increase of larger tumors and decrease in the female/male ratio, which could be secondary to the influence of unidentified environmental factors.

Cáncer de cavum. Experiencia institucional / Cancer of cavum. Institutional experience

Los carcinomas epidermoides de cabeza y cuello son un grupo poco frecuente de neoplasias, en los Estados Unidos representan aproximadamente el 3% de todos los tumores. El cáncer de cavum se diferencia de otros tumores de cabeza y cuello por su epidemiología, histología, historia natural y respuesta al tratamiento. Presenta una marcada variación geográfica debido a su etiología multifactorial. En las áreas endémicas, la incidencia y la mortalidad han disminuido en los últimos 30 años. Esto probablemente se deba a cambios en el estilo de vida y avances en la radioterapia (RT) y quimioterapia (QT) sistémica (AU)

Epidermoid carcinomas of the head and neck are a rare group of tumors, in the United States they account for 3% of all cancers. Nasopharyngeal carcinoma differs from others head and neck squamous cells carcinomas in epidemiology, natural history, and response to treatment. Nasopharyngeal carcinoma displays a distinct racial and geographic distribution, which is reflective of its multifactorial etiology. The incidence and mortality has declined over the past 30 years in many endemic areas. This finding is probably a result of a combination of lifestyle modification and advances in radiotherapy and effective systemic agents (AU)

Thyroid lipomatosis in a 36-year-old patient with rheumatoid arthritis and a kidney transplant.

UNLABELLED: Thyroid lipomatosis is a rare disease, as a total of 20 cases have been described in the literature. It is characterized by diffuse infiltration of the stroma by mature adipose tissue and by progressive growth that produces different degrees of compressive symptoms. Our aim is to present the case of a 36-year-old woman who consulted because of dyspnea caused by a multinodular goiter. She underwent surgery with the presumptive diagnosis of a malignant neoplasia, but the pathological examination of the surgical specimen established the diagnosis of thyroid lipomatosis. LEARNING POINTS: Thyroid lipomatosis is a rare, benign disease characterized by diffuse infiltration of the stroma by mature adipose tissue.The pathophysiology of diffuse proliferation of adipose tissue in the thyroid gland is unclear.Thyroid lipomatosis is clinically manifested by a progressive enlargement of the thyroid that can involve the airway and/or upper gastrointestinal tract, producing dyspnea, dysphagia, and changes in the voice.Given the rapid growth of the lesion, the two main differential diagnoses are anaplastic carcinoma and thyroid lymphoma.Imaging studies may suggest a differential diagnosis, but a definitive diagnosis generally requires histopathological confirmation after a thyroidectomy.

Dried apples enriched with mandarin juice by vacuum impregnation improve antioxidant capacity and decrease inflammation in obese children / La ingestión de un producto derivado de manzana deshidratada enriquecido con zumo de mandarina mediante tecnología de impregnación al vacío mejora la capacidad antioxidante y disminuye la inflamación en los niños obesos

Background: A favorable effect over development of degenerative diseases is derived of an adecuate intake of fruit and vegetables, mainly due to their antioxidant compounds OBJECTIVES: The goal of this study was to test the effect in vivo over oxidant status and inflammation in obese children of a novel food product made of dried apples enriched with mandarin juice by vacuum impregnation. METHODS: A four-week intervention study was conducted in 41 obese children (> 2 standard deviation score-body mass index). Participants were instructed to follow their usual diet supplemented with 40 g/day of the developed product. Anthropometric parameters were determined including body mass index, waist circumference and estimations of body fat percentage using bioelectrical impedance. Dietary intake was assessed by questionnaire. Metabolic risk factors (blood pressure, lipid profile, glucose and insulin resistance) were recorded. To determine oxidant status, plasma total antioxidant capacity and 8-hydroxydeoxyguanosine, as marker of oxidative damage to DNA, were investigated. High-sensitive C-reactive protein, tumor necrosis factor-Alpha, and interleukins 6 and 1-Alpha were measured as inflammatory markers. Measurements were collected at baseline and at the end of the intervention period. RESULTS: Significant improvement in systolic blood pressure and lipid profile after intervention period was noted. A significant increase in the antioxidant capacity of plasma (ABTS and FRAP assays) and reductions in DNA oxidative damage and inflammatory markers were also found. CONCLUSION: Overall, adding the product to the diet contributes to ameliorate oxidant and inflammatory status in obese children and several risk factors for atherosclerosis (AU)

Antecedentes: Una adecuada ingesta de vegetales previene el desarrollo de enfermedades degenerativas, principalmente debido a sus compuestos antioxidantes. Objetivo: Evaluamos el efecto in vivo en los niños obesos de un nuevo producto alimenticio hecho de manzanas deshidratadas enriquecidas con zumo de mandarina mediante impregnación a vacío. Métodos: Estudio prospectivo longitudinal de cuatro semanas de duración. Se estudiaron 41 niños obesos que suplementaron su dieta habitual con 40 g/día del producto desarrollado. Se determinaron parámetros antropométricos (índice de masa corporal, circunferencia de la cintura) y estimación de la de grasa corporal con impedancia bioeléctrica. La ingesta dietética se evaluó por cuestionario. Se registraron factores de riesgo metabólico (presión sanguínea, perfil lipídico, glucosa y resistencia insulínica). El estado oxidante se investigó mediante la capacidad antioxidante total del plasma y la 8-hydroxideoxiguanosina (marcador de daño oxidativo al ADN) y como marcadores de inflamación valoramos la proteína C-reactiva ultrasensible, el factor de necrosis tumoral-Alpha y las interleukinas 6 y 1-Alpha. Las mediciones se recogieron al inicio y al final del período de intervención. Resultados: Encontramos una mejoría significativa en la presión arterial sistólica y en el perfil lipídico después del período de intervención. Igualmente demostramos un aumento significativo de la capacidad antioxidante del plasma, una reducción del daño oxidativo del ADN y de los marcadores inflamatorios. Conclusión: La adición a la dieta del producto elaborado con manzana deshidratada, y enriquecido con zumo de mandarina mediante impregnación al vacío, contribuye a mejorar el estado oxidante e inflamatorio en los niños obesos, así como diversos factores de riesgo cardiometabólico (AU)