Oral Immunotherapy With Egg and Milk: Changes in Peripheral Serum Cytokines Are Not Predictive Factors for Severe Adverse Reactions or for the Final Report.

BACKGROUND: Oral immunotherapy (OIT) is a new approach in patients with food allergy. Various immunological mechanisms underlie the reversal of food allergy. In this paper, we study possible changes in peripheral cytokine patterns during OIT. METHODS: Determinations of cytokines in peripheral blood were made in children who had milk or egg allergy and who received OIT. The determinations were made before and after OIT, and again following a final repeat oral challenge a month after a diet excluding the culprit food. RESULTS: No significant changes were registered in the cytokines studied (IL-2, IL-4, IL-6, IL-10, IL-12, IL-17, IFNγ, and TNF) at any of the 3 time points. Similarly, no differences in cytokine pattern were observed between children who had presented anaphylaxis during OIT and those who overcame or did not overcome the final oral challenge. DISCUSSION: Peripheral cytokines do not undergo significant changes during the OIT process. They are not predictors of serious adverse reactions or the final result of the OIT.

An intensive model of care for hepatitis C virus screening and treatment with direct-acting antivirals in people who inject drugs in Nairobi, Kenya: a model-based cost-effectiveness analysis.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) treatment is essential for eliminating HCV in people who inject drugs (PWID), but has limited coverage in resource-limited settings. We measured the cost-effectiveness of a pilot HCV screening and treatment intervention using directly observed therapy among PWID attending harm reduction services in Nairobi, Kenya. DESIGN: We utilized an existing model of HIV and HCV transmission among current and former PWID in Nairobi to estimate the cost-effectiveness of screening and treatment for HCV, including prevention benefits versus no screening and treatment. The cure rate of treatment and costs for screening and treatment were estimated from intervention data, while other model parameters were derived from literature. Cost-effectiveness was evaluated over a life-time horizon from the health-care provider's perspective. One-way and probabilistic sensitivity analyses were performed. SETTING: Nairobi, Kenya. POPULATION: PWID. MEASUREMENTS: Treatment costs, incremental cost-effectiveness ratio (cost per disability-adjusted life year averted). FINDINGS: The cost per disability-adjusted life-year averted for the intervention was $975, with 92.1% of the probabilistic sensitivity analyses simulations falling below the per capita gross domestic product for Kenya ($1509; commonly used as a suitable threshold for determining whether an intervention is cost-effective). However, the intervention was not cost-effective at the opportunity cost-based cost-effectiveness threshold of $647 per disability-adjusted life-year averted. Sensitivity analyses showed that the intervention could provide more value for money by including modelled estimates for HCV disease care costs, assuming lower drug prices ($75 instead of $728 per course) and excluding directly-observed therapy costs. CONCLUSIONS: The current strategy of screening and treatment for hepatitis C virus (HCV) among people who inject drugs in Nairobi is likely to be highly cost-effective with currently available cheaper drug prices, if directly-observed therapy is not used and HCV disease care costs are accounted for.

Diet and prevalence of atopic eczema in 6 to 7-year-old schoolchildren in Spain: ISAAC phase III.

BACKGROUND: The prevalence of atopic dermatitis (AD), a chronic skin disease, has increased substantially in recent decades, and different factors have been implicated in its etiology. Although dietary habits are being investigated, few conclusive findings have been reported. Nevertheless, increased consumption of polyunsaturated fatty acids (PUFA) and a diet poor in antioxidants have been related to AD. OBJECTIVES: The objectives of this study were to investigate the association between AD, the intake of different foods, and the effect of a Mediterranean diet among Spanish schoolchildren aged 6 to 7. METHODS: We performed a cross-sectional study with 20 106 schoolchildren aged 6-7 years from 10 different areas of Spain. The participation rate was 76.50%. The prevalence of AD was assessed using the International Study of Asthma and Allergies in Childhood questionnaire and the criteria of the Spanish Academy of Dermatology. To calculate the Mediterranean diet score, we classified food into 2 groups: Mediterranean food, including fruit, seafood, vegetables, pulses, cereals, pasta, rice, and potatoes; and non-Mediterranean food, including meat, milk, and fast food. RESULTS: Milk was negatively associated with AD. Butter and nuts also were negatively associated, although statistical significance was only reached when these foods were consumed 3 or more times a week. CONCLUSIONS: We found no association between the Mediterranean diet score and AD and a positive association between AD and obesity.

A biosensor capable of identifying low quantities of breast cancer cells by electrical impedance spectroscopy.

Breast cancer (BC) is a malignant disease with a high prevalence worldwide. The main cause of death is not the primary tumor, but instead the spread of tumor cells to distant sites. The aim of the present study was to examine a new method for the detection of cancer cells in aqueous medium using bioimpedance spectroscopy assisted with magnetic nanoparticles (MNP's) exposure to a constant magnetic field. The spectroscopic patterns were identified for three breast cancer cell lines. Each BC cell line represents a different pathologic stage: the early stage (MCF-7), invasive phase (MDA-MB-231) and metastasis (SK-BR-3). For this purpose, bioimpedance measurements were carried out at a certain frequency range with the aid of nanoprobes, consisting of magnetic nanoparticles (MNPs) coupled to a monoclonal antibody. The antibody was specific for the predominant cell surface protein for each cell line, which was identified by using RT-qPCR and flow cytometry. Accordingly, EpCAM corresponds to MCF-7, MUC-1 to MDA-MB-231, and HER-2 to SK-BR-3. Despite their low concentrations, BC cells could be detected by impedance spectroscopy. Hence, this methodology should permit the monitoring of circulating tumor cells (CTC) and therefore help to prevent recurrences and metastatic processes during BC treatment.

How the presence of rhinoconjunctivitis and the severity of asthma modify the relationship between obesity and asthma in children 6-7 years old.

BACKGROUND: The association between asthma and obesity in children, and the effect modification of allergy on this association have not been fully established. Aims The objective of the study was to know the effect modification of the severity of asthma and of the coexistence of rhinoconjunctivitis (RC) in the relationship between obesity and asthma. METHODS: A cross-sectional study of 17 145 schoolchildren 6-7 years old from eight Spanish cities who had completed information on height and weight of the ISAAC phase III questionnaire, which also included questions about asthma and RC symptoms and on various risk factors. Body mass index (BMI) was used to define obesity according to international standards. Two different logistic regressions, using current occasional asthma (COA) and current severe asthma (CSA) as dependent variables, were made stratifying for gender and for the coexistence of RC and controlling for age, older and younger siblings, exercise, mother's education, truck traffic, cat/dog during the first year of life and smoking father or mother. RESULTS: Obesity was a risk factor of CSA without RC, both for boys (1.92, CI 95% 1.13-3.25) and for girls (2.99, CI 95% 1.68-5.32). Every BMI unit increment increased by 6.7% the risk of CSA without RC in boys and by 12.4% in girls. Obesity was not a risk factor for CSA with RC. The association between COA and obesity was weaker and the coexistence of RC did not modify it greatly. CONCLUSIONS: Obese schoolchildren are more at risk of suffering from non-allergic asthma than the non-obese subjects.

Electrical bioimpedance spectroscopy as biosensor technique to identify cells lineages and cell differentiation process.

The identification and characterization of diverse cells types and cell differentiation process requires complex techniques as flow cytometry, immunocytochemistry and the exploration of molecular markers; such techniques require infrastructure and qualified personnel. The objective of this study was to analyze the use of Electrical Bioimpedance Spectroscopy (EBIS) measurements as a non-complex alternative technique to identify populations of undifferentiated mouse Pluripotent Stem Cells (mPSCs), Mouse Embryonic Fibroblasts (MEFs) and the differentiation process from preadipocytes (3T3-L1) to mature adipocytes. EBIS measurements were compared in populations of cells which were characterized previously using microscopy. The results indicate that EBIS technique has a potential sensitivity at certain frequency range to discriminate between both evaluated cell populations and some differentiation process. Additional studies with different concentrations to evaluate quantitatively the sensitivity and specificity of the proposed technique are recommended.

[Bronchodilators via metered-dose inhaler with spacer in the pediatric emergency department: what is the dosage?]. / Broncodilatadores inhalados mediante MDI con cámara espaciadora en urgencias pediátricas: cuál es la dosis?

INTRODUCTION: Bronchodilators administrated through a metered-dose inhaler (MDI) with spacer are as effective as nebulizers in the treatment of acute asthma exacerbations in childhood. However, consensus is lacking on the most suitable dosage. OBJECTIVE: To assess the effectiveness of distinct salbutamol and terbutaline doses delivered via an MDI with spacer for the treatment of acute asthma in the pediatric emergency department. METHODS: This was a prospective, double-blind randomized study. All consecutive children (n = 324) between 2 and 14 years of age with acute asthma exacerbations treated in the pediatric emergency department between October 1 and November 30, 2004, were included. Two treatment groups were established: one group received a number of puffs equivalent to half the child's weight (1 puff of salbutamol = 100 microg and 1 puff of terbutaline = 250 microg) and the other group received a number of puffs equivalent to one-third of the child's weight. RESULTS: Three hundred twenty-four episodes were studied; there were 164 children in the first group and 160 in the second. There were no significant differences between the two groups in the mean (6 SD) age (58.34 +/- 34.72 vs 66.04 +/- 36.45 months), arterial oxygen saturation (95.49 +/- 1.93 vs 95.56 +/- 1.97) or pulmonary score (4.04 +/- 1.55 vs 3.97 +/- 1.51) at recruitment and after treatment in the emergency department (arterial oxygen saturation [96.34 +/- 1.60 vs 96.18 +/- 1.77], pulmonary score [1.87 +/- 1.33 vs 1.64 +/- 1.31]). The number of doses administered (2.17 +/- 0.91 vs 2.24 +/- 1.00) and the hospitalization rate (8.56 % vs 6.87 %) were also similar in both groups. CONCLUSIONS: The distinct bronchodilator doses administered via an MDI with spacer showed similar effectiveness. These findings should contribute to a reevaluation of the use of high doses of bronchodilators, at least in most acute asthma exacerbations in children.

[Geographic variation in the prevalence of asthma symptoms in Spanish children and adolescents. International Study of Asthma and Allergies in Childhood (ISAAC) Phase 3, Spain]. / Variaciones geograficas en la prevalencia de sintomas de asma en los ninos y adolescentes espanoles. International Study of Asthma and Allergies in Childhood (ISAAC) fase III Espana.

OBJECTIVE: To analyze geographic variations in the prevalence of symptoms related to asthma in Spanish children and adolescents. POPULATION AND METHODS: In 2001 and 2002, the Spanish arm of the International Study of Asthma and Allergies in Childhood (ISAAC) Phase 3 collected information on 28 445 children in the age bracket of 6-7 years in 10 metropolitan areas (A Coruña, Asturias, Barcelona, Bilbao, Cartagena, Castellón, Madrid, Pamplona, San Sebastián, and Valencia) and on 31 257 adolescents in the bracket 13-14 years in 11 areas (the previously named areas plus Valladolid). An asthma symptom questionnaire was filled in by parents or the adolescents themselves. Differences in symptoms between geographic areas were analyzed by fitting a logistic regression model. The relationship between symptoms and age was analyzed by linear correlation. RESULTS: The prevalence of recent wheezing (last 12 months) ranged from 7.1% to 12.9% among 6-7-year-olds and from 7.1% to 15.3% among the 13-14-year-olds. The greatest risk of recent wheezing was observed for children in A Coruña (odds ratio [OR] =1.96 in comparison with the area of lowest prevalence; 95% confidence interval [CI], 1.65-2.33) and Bilbao (OR=1.83; 95% CI, 1.54-2.18) and for adolescents in A Coruña (OR=2.38; 95% CI, 2.04-2.79) and Asturias (OR=2.37; 95% CI, 2.03-2.77). A strong correlation (r=0.72) was observed between the prevalence of recent wheezing and age in each of the geographic areas. CONCLUSIONS: Considerable geographic variation in the prevalence of asthma symptoms can be seen in Spain even among young children. Symptoms are more frequent in children and adolescents who live on the Spain s northern Atlantic coast.

[Clinical and epidemiological study of community-acquired pneumonia in children aged less than 5 years old]. / Estudio clínico y epidemiológico de la neumonía adquirida en la comunidad en niños menores de 5 años de edad.

OBJECTIVE: To describe the clinical characteristics of community-acquired pneumonia and associated morbidity in children under 5 years old. PATIENTS AND METHOD: We performed a prospective epidemiological study in 12 primary care clinics and two pediatric emergency departments in Vizcaya, Spain. Demographic, clinical, radiological, laboratory and treatment data were recorded at diagnosis. Different pneumonia groups were established on the basis of radiological images (lobar pattern), total leucocyte count (> 15,000/ml) and C-reactive protein value (> 80 mg/l). These groups ranged from definitive pneumococcal pneumonia (pneumococcus isolated in usually sterile specimens) to pneumonia of probable non-pneumococcal etiology. All patients were followed-up for 7 to 15 days after diagnosis to ascertain outcome. RESULTS: Between February and April 2003, 412 children with pneumonia were enrolled. The mean age was 33.4 6 15.34 months and 21 % of the patients had received the pneumococcal conjugate vaccine. Overall 20 % had general malaise and 14.6 % required admission, with a mean length of hospital stay of 4.10 +/- 2.21 days. The mean length of treatment was 9.51 +/- 2.44 days and the mean number of visits to the primary care pediatrician was 2.02 6 1.10. Fifty-three patients (12.9 %) had definitive or highly probable pneumococcal pneumonia and these children had higher temperature (38.74 +/- 0.84 vs 38.38 +/- 0.94 degrees C), a higher percentage of general malaise (50.9 % vs 15.3 %) and a higher hospitalization rate (41.5 % vs 10.5 %). CONCLUSIONS: Community-acquired pneumonia in children under 5 years old provokes high morbidity. According to clinical, radiological and laboratory data, suspected pneumococcal pneumonia seems more severe than forms probably caused by other agents.

[Time trends and geographical variations in the prevalence of symptoms of allergic rhinitis in 6-7-year-old children from eight areas of Spain according to the ISAAC]. / Tendencia temporal y variaciones geográficas de la prevalencia de síntomas de rinitis alérgica en escolares de 6-7 años de ocho áreas españolas, según el ISAAC.

BACKGROUND: Phase III of the International Study of Asthma and other Allergies in Childhood (ISAAC) was carried out in schoolchildren aged 6-7 years from eight areas of Spain to estimate time trends and geographic variations in the prevalence of symptoms of allergic rhinitis (AR). MATERIAL AND METHOD: A standard and validated questionnaire was used following ISAAC methodology and was completed by the schoolchildren's parents. The prevalence of symptoms of AR in Phase I (1993-1994) and Phase III (2001-2002) was compared. Eight centers participated: Asturias, Barcelona, Bilbao, Cartagena, Castellón, Madrid, Pamplona and Valencia. Poisson regression was used in the analysis. RESULTS: A total of 25,113 schoolchildren were studied with a median participation of 81.7 %. In all centers, AR symptoms tended to increase, with a prevalence ratio of rhinoconjunctivitis in the previous year of 1.61 (95 % confidence interval: 1.48-1.76) when both phases, adjusted by gender, center, and seasonal variation, were compared. The prevalence of AR symptoms was higher in boys than in girls. Wide variations in the prevalence of AR were observed across centers with a higher prevalence in Asturias, Madrid, Cartagena and Bilbao. Lower prevalences were reported in Barcelona, Castellón and Pamplona. CONCLUSIONS: There seems to have been a general increase in AR symptoms. Substantial variations between centers suggested that there may be local differences in risk factors. Intense research will be required for satisfactory preventive actions.

Componentes Principales mediante Espectroscopia FTIR como Técnica de Caracterización Innovadora durante la Diferenciación de Células Madre Pluripotentes a Células Pancreáticas / Principal Components by FTIR Spectroscopy as Innovative Characterization Technique during Differentiation of Pluripotent Stem Cells to Pancreatic Cells

Resumen: Dos de los grandes retos en la biología de las Células Madre (CM) y la Medicina Regenerativa, son el control en la diferenciación de estas células y asegurar la pureza de las células diferenciadas, por lo que es necesario contar con técnicas rápidas, eficientes y precisas para la caracterización de CM y su diferenciación a diferentes linajes celulares. El objetivo de este trabajo fue analizar Células Madre Pluripotentes (CMP) y Células Pancreáticas Diferenciadas (CPD) mediante espectroscopía Infrarroja por Transformada de Fourier (FTIR) y Análisis de Componentes Principales (ACP). Para ello se diferenciaron CMP a CPD, caracterizando el proceso de diferenciación a los días 0, 11, 17 y 21 mediante microscopía óptica y espectroscopia vibracional. Los espectros FTIR se analizaron con el método multivariado de ACP, utilizando su segunda derivada en las regiones de proteínas, carbohidratos y ribosas. Los resultados indican que el ACP permite caracterizar y discriminar CMP y CPD en sus diferentes etapas de diferenciación en las regiones espectrales analizadas. Con lo anterior concluimos que el ACP permite caracterizar química y estructuralmente CMP y diferentes etapas de su diferenciación en una forma rápida, precisa y no invasiva.

Abstract: Two of the greatest challenges in Stem Cells (SCs) biology and regenerative medicine, are differentiation control of SCs and ensuring the purity of differentiated cells. In this sense, fast, efficient and accurate techniques for SCs characterization and their differentiation into different cell lineages are needed. The aim of this study was to analyse Pluripotent Stem Cells (PSCs) and Differentiated Pancreatic Cells (DPCs) by Fourier Transform Infrared (FTIR) spectroscopy and Principal Component Analysis (PCA). For this purpose, we differentiated PSCs toward DPCs, characterizing the differentiation process at different stages (0, 11, 17 and 21 days) through light microscopy and vibrational spectroscopy. FTIR spectra were analysed with the multivariate method of PCA, using the second derivatives in the protein, carbohydrate and ribose regions. The results indicate that the PCA allows to characterize and discriminate PSCs and DPCs at different stages of differentiation in the analysed spectral regions. From these results, we concluded that the PCA allows the chemically and structural characterization of PSCs and the different stages of their differentiation in a fast, accurate and non-invasive way.

Evaluación de Termografía Tisular Diferenciada en Mama como Potencial Técnica para Asistir la Detección de Cáncer / Evaluation of Thermography Differentiated in Breast Tissue as Potential Technique to Assist Cancer Detection

Diversos grupos han propuesto el procesamiento de imágenes termográficas para detección de Cáncer de Mama (CaMa). Angiogénesis y vascularización dependientes del ciclo menstrual, edad e Índice de Masa Corporal (IMC) modifican la temperatura absoluta en la superficie tisular sin estar necesariamente asociadas a malignidad, en éste estudio proponemos la Termografía Tisular Diferenciada (TTD) en mama con respecto a su contralateral en espejo con el fin de observar diferencias térmicas características de malignidad. El presente trabajo evalúa la posibilidad de emplear la TTD como potencial técnica para asistir la detección de CaMa. Se muestrearon 110 mujeres voluntarias entre 40 y 60 años de edad segmentadas en dos grupos experimentales: grupo sanas (n=90) y grupo con CaMa (n=20) previamente diagnosticadas por mastografía e histopatología. Imágenes termográficas de ambas mamas fueron adquiridas con una cámara infrarroja y se estimó la TTD en relación a la mama contralateral de la misma paciente, se realizó un análisis de sensibilidad y especificidad y se comparó con el diagnóstico radiológico a través de curvas ROC tomando como referencia el diagnóstico histopatológico. La TTD en mama mostró rangos dinámicos diferenciables entre condiciones de malignidad respecto a benignidad. El análisis ROC mostró valores de sensibilidad y especificidad para el estimado TTD del 70% y 54% mientras que para el diagnóstico radiológico fue del 70% y 96%, respectivamente. La TTD muestra viabilidad técnica para asistir la detección de CaMa.

Several groups have proposed thermographic image processing for Breast Cancer (BC) detection. Angiogenesis and vascularization of menstrual cycle dependent, as well as age and Body Mass Index change the absolute temperature in the tissue surface without necessarily being associated with malignancy. We have proposed the Differentiated Tissue Thermography (DTT) in breast regarding its contralateral mirror in order to observe differences in temperature characteristics of malignancy. This study evaluates the possibility of using breast DTT as a potential technique to assist the detection of BC. We sampled 110 female volunteers between 40 and 60 years old segmented into two experimental groups: healthy group (n=90) and BC group (n=20), which were diagnosed by mammography and histopathology. Thermal images of both breasts were acquired with an infrared camera and the DTT was estimated relative to its contralateral breast in the same patient. A sensitivity and specificity analysis was developed and the DTT was compared with the radiological diagnosis by ROC curves with the histopathological report as reference. The DTT values showed distinguishable dynamic ranges between malignant and healthy conditions. ROC analysis showed sensitivity and specificity values for DTT of 70% and 54% while for the radiological diagnosis was 70% and 96% respectively. DTT showed technical viability to assist BC detection.

Parents' smoking habit and prevalence of atopic eczema in 6-7 and 13-14 year-old schoolchildren in Spain. ISAAC phase III.

BACKGROUND AND AIMS: Atopic eczema (AE) is the most frequent inflammatory skin disease in childhood in the western world. Several studies have reported a significant increase of prevalence in recent decades and the environmental factors implicated in its aetiology, including environmental tobacco smoke. This study aims to investigate the possible association of AE prevalence in Spanish schoolchildren aged 6-7 and 13-14 years in relation to their parents' smoking habits. METHODS: We conducted a cross-sectional population-based study with 6-7 year-old (n = 27805) and 13-14 year-old (n = 31235) schoolchildren from 10 Spanish centres. AE prevalence was assessed using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, and the Spanish Academy of Dermatology criteria, used in Spain to diagnose AE. RESULTS: An association was found in school-children aged 6-7 (adjusted for gender, presence of asthma, presence of rhinitis, siblings and mother's level of education) between AE being clinically diagnosed with the mother's smoking habit (RPRa 1.40, 1.10-1.78) and there being more than 2 smokers at home (RPRa 1.34, 1.01-1.78). Regarding the presence of itchy rash, an association was observed with fathers who smoke (RPRa 1.40, 1.13-1.72). Among the 13-14 year-olds, no association was observed in relation to either clinically diagnosed AE or the appearance of itchy rash with parents' smoking habit. CONCLUSIONS: Our results indicate the risk for children of being exposed to environmental tobacco smoke in terms of AE, especially when they are younger.

[Proposal for a scale for the assessment and treatment of febrile convulsions]. / Propuesta de una escala para valoración y tratamiento de las convulsiones febriles.

Prophylaxis of febrile convulsions has been very controversial. Often this prophylaxis is given based upon subjective criteria and even in the same Department of Paediatrics, criteria are not uniformly carried out. We consider of great interest to value some circumstances of the febrile convulsions, which could be worth for valorating recidives. We have quantified some parameters, that can be obtained easily. Those have systematically been used in our Department, leading us to establish and score to determine the risk factors that lead us to use or not a prophylactic treatment in children with febrile convulsions.

[Prevalence and severity of asthma in 13-14-year-old children in Bilbao]. / Prevalencia y gravedad del asma en la población infantil de 13-14 años de Bilbao.

OBJECTIVE: The objective of this study was to know the prevalence and severity of bronchial asthma in 13-14 year old children living in Bilbao, a seacoast industrial town in the North of Spain. PATIENTS AND METHODS: A sample of 13-14 year old children living in Bilbao was studied. Random sampling amongst school centers was done. Fifty-eight centers were included and a total of 3,578 children between 13-14 years old were studied. The International Study of Asthma and allergy in Children (ISAAC) written and video questionnaires were used. Statistical analysis included bar diagrams, qualitative variable frequencies and the Chi 2 test to study the contrast and the association between variables. The statistical significance level was 95%. The relative risk according to sex was obtained. RESULTS: The questionnaires that were valid (3,213) represented 89% of the selected sample. The accumulated asthma prevalence was 18.9%. The actual asthma prevalence (asthma during the last year) was 11.9%. Severe asthma was present in 11.9% of the children. Asthma had been previously diagnosed in 16.3% of the children. The relative risk of being diagnosed was 1.39 for males. CONCLUSIONS: These figures are similar to those obtained in other populations with the same geographic and climate characteristics.