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Despite of the capacity that several drugs have for specific inhibition of the androgen receptor (AR), in most cases, PCa progresses to an androgen-independent stage. In this context, the development of new targeted therapies for prostate cancer (PCa) has remained as a challenge. To overcome this issue, new tools, based on nucleic acids technology, have been developed. Aptamers are small oligonucleotides with a three-dimensional structure capable of interacting with practically any desired target, even large targets such as mammalian cells or viruses. Recently, aptamers have been studied for treatment and detection of many diseases including cancer. In PCa, numerous works have reported their use in the development of new approaches in diagnostics and treatment strategies. Aptamers have been joined with drugs or other specific molecules such as silencing RNAs (aptamer-siRNA chimeras) to specifically reduce the expression of oncogenes in PCa cells. Even though these studies have shown good results in the early stages, more research is still needed to demonstrate the clinical value of aptamers in PCa. The aim of this review was to compile the existing scientific literature regarding the use of aptamers in PCa in both diagnosis and treatment studies. Since Prostate-Specific Membrane Antigen (PSMA) aptamers are the most studied type of aptamers in this field, special emphasis was given to these aptamers.

Introduction: There are various scales designed to determine the risk of malnutrition at hospital admission in children. However, most of these instruments are developed and published in English. Their cross-cultural adaptation and validation being mandatory in order to be used in our country., Objectives: Cross-culturally adapt three scales designed to determine the risk of malnutrition linked to the disease and determine the validity of their content., Material and Methods: Cross-cultural adaptation using the translation-back-translation method in accordance with the recommendations of the International Test Commission Guidelines for Translating and Adapting Tests. Content validity was measured by a panel of experts (under seven basic selection criteria adapted from the Fehring model) who evaluated each item of the scales by measuring 4 criteria: ambiguity, simplicity, clarity and relevance. With the extracted score, Aiken's V statistic was obtained for each item and for the complete scales., Results: Starting from three independent translations per scale, 3 definitive versions in Spanish of the PNRS, STRONGkids and STAMP scales were obtained semantically equivalent to their original versions. The PNRS and STRONGkids scales presented an Aiken's V greater than 0.75 in all their items, while the STAMP scale presented a value less than 0.75 for the item "weight and height"., Conclusion: This study provides the transculturally adapted Spanish versions of the PNRS, STRONGkids and STAMP scales. The PNRS and STRONGkids scales present valid content to be applied in the state hospital context. STAMP requires the adaptation of its item "weight and height" to consider its use in a Spanish child population adequate., (Copyright © 2021 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

World Health Organization (WHO) has prioritized the infectious emerging diseases such as Coronavirus Disease (COVID-19) in terms of research and development of effective tests, vaccines, antivirals, and other treatments. Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), the etiological causative agent of COVID-19, is a virus belonging to risk group 3 that requires Biosafety Level (BSL)-3 laboratories and the corresponding facilities for handling. An alternative to these BSL-3/-4 laboratories is to use a pseudotyped virus that can be handled in a BSL-2 laboratory for study purposes. Recombinant Vesicular Stomatitis Virus (VSV) can be generated with complementary DNA from complete negative-stranded genomic RNA, with deleted G glycoprotein and, instead, incorporation of other fusion protein, like SARS-CoV-2 Spike (S protein). Accordingly, it is called pseudotyped VSV-SARS-CoV-2 S. In this review, we have described the generation of pseudotyped VSV with a focus on the optimization and application of pseudotyped VSV-SARS-CoV-2 S. The application of this pseudovirus has been addressed by its use in neutralizing antibody assays in order to evaluate a new vaccine, emergent SARS-CoV-2 variants (delta and omicron), and approved vaccine efficacy against variants of concern as well as in viral fusion-focused treatment analysis that can be performed under BSL-2 conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Salazar-García, Acosta-Contreras, Rodríguez-Martínez, Cruz-Rangel, Flores-Alanis, Patiño-López and Luna-Pineda.)

Background: Studies on childhood obesity mainly focus on the genetic component and on the lifestyle that may be associated with the development of obesity. However, the study of perinatal factors in their programming effect toward future obesity in children or adults is somewhat more recent, and there are still mechanisms to be disentangled., Summary: In this narrative review, a comprehensive route based on the influence of some early factors in life in the contribution to later obesity development is presented. Maternal pre-pregnancy BMI and gestational weight gain have been pointed out as independent determinants of infant later adiposity. Lifestyle interventions could have an impact on pregnant mothers through epigenetic mechanisms capable of redirecting the genetic expression of their children toward a future healthy weight and body composition and dietary-related microbiome modifications in mothers and newborns might also be related. After birth, infant feeding during the first months of life is directly associated with its body composition and nutritional status. From this point of view, all the expert committees in the world are committed to promote exclusive breastfeeding up to 6 months of age and to continue at least until the first year of life together with complementary feeding based on healthy dietary patterns such as Mediterranean Diet., Key Messages: To develop future effective programs to tackle early obesity, it is necessary not only by controlling lifestyle behaviors like infant feeding but also understanding the role of other mechanisms like the effect of perinatal factors such as maternal diet during pregnancy, epigenetics, or microbiome., (© 2021 S. Karger AG, Basel.)

Dp71 and Dp40 are the main products of the DMD gene in the central nervous system, and they are developmentally regulated from the early stages of embryonic development to adulthood. To further study the roles of Dp71 and Dp40 during cell proliferation and neural differentiation, we analyzed Dp71/Dp40 isoform expression at the mRNA level by RT-PCR assays to identify alternative splicing (AS) in the isoforms expressed in rat neural stem/progenitor cells (NSPCs) and in differentiated cells (neurons and glia). We found that proliferating NSPCs expressed Dp71d, Dp71d Δ71 , Dp71f, Dp71f Δ71 , Dp71d Δ74 and Dp40, as well as two Dp40 isoforms: Dp40 Δ63,64 and Dp40 Δ64-67 . In differentiated cells we also found the expression of Dp71d, Dp71d Δ71 , Dp71f, Dp71f Δ71 and Dp40. However, the expression frequencies were different in both stages. In addition, in differentiated cells, we found Dp71f Δ71-74 , and interestingly, we did not find the expression of Dp71d Δ74 or the newly identified Dp40 isoforms. In this work we show that NSPC differentiation is accompanied by changes in Dp71/Dp40 isoform expression, suggesting different roles for these isoforms in NSPCs proliferation and neuronal differentiation, and we describe, for the first time, alternative splicing of Dp40., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest The authors have no conflicts of interest to declare.

Introduction: Although changes in liver function tests can be non-specific in numerous clinical conditions, they can be the first sign of a potentially serious disease in an asymptomatic patient., Material and Methods: Retrospective cohort study, performed by reviewing the records of children of a reference hospital central laboratory with alanine aminotransferase enzyme (ALT) elevation during a 6-month aleatory period., Results: 572 blood tests with serum ALT elevation corresponding to 403 patients have been assessed during the period studied. 98 patients were excluded for presenting abnormal liver test before the study period of comorbidity that could produce ALT elevation. The remaining 305 patients, 22.6% were diagnosed with a medical condition during the first blood test that explained the ALT elevation, although only 33.3% of them were followed up until verifying their normalisation. Final study sample consists of 236 patients with abnormal liver test without apparent liver disease. Adequate follow-up was found only in 29% of them. From this group, 9 patients (13%) were diagnosed with liver disease. The rest of the samples were not properly monitored. In patients with higher serum ALT levels, follow-up was early and more appropriate., Conclusions: In our area, most children without apparent liver disease are no properly monitored. Therefore, an opportunity to diagnosis and treat a potential liver disease was lost in a great number of children. All children with unexplained hypertransaminasaemia must be studied., (Copyright © 2021 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Patients with moderate-severe cerebral palsy require the support of their caregivers to carry out the activities of daily living (ADLs)., Objectives: To describe the comorbidities, need for care in children with cerebral palsy and to analyse the influence of the degree of motor involvement, nutritional status and other neurological disorders., Methods: Cross-sectional and observational study. Patients with cerebral palsy degrees III-IV-V according to the Gross Motor Function Classification System (GMFCS) have been studied. A record of comorbidities has been made and body composition has been studied using anthropometry and bioimpedance. In addition, a caregiver burden survey on ADLs has been carried out (10 items on the different actions: hygiene, clothing, transfers, sleeping and feeding). Which variables have the greatest influence on the perception of difficulty in performing ADLs have been studied., Results: A total of 69 patients (50.7% women, mean age 10.46 ± 0.4 years) were analysed, with GMFCS grades: grade III 36.2% (N=25), grade IV 29.0% (N=20), grade V 34.8% (N=24). A relationship was found between the caregiver burden score and GMFCS grade (P=0.003) and intellectual disability (P<0.001). However, regardless of the degree of GMFCS and intellectual disability, there is greater difficulty in performing ADLs in relation to lower values in weight (Z-score) (P=0.028), fat mass (kg) (P=0.035), fat mass (%) (P=0.094), body mass index (Z-score) (P=0.086)., Conclusions: In addition to the degree of clinical impairment, nutritional status is a factor that influences the caregiver's difficulty in performing the ADLs in cerebral palsy patients on which we can act to improve this problem., (Copyright © 2021 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Most of the studies analyzing the effect of moderate to vigorous physical activity (MVPA) on children's health do not contain information on early stages or do not use accurate methods. We investigated the association between PA and body composition using objective methods, perinatal data, lifestyle behaviors, and World Health Organization (WHO) physical activity (PA) recommendations. The CALINA study is a longitudinal observational cohort study of children born in Aragon (Spain) in 2009. A total of 308 7-year-old children (52.3% boys) were assessed. We used dual-energy X-ray absorptiometry (DXA) and accelerometry. Rapid weight gain until 12 months and lifestyle behaviors were considered as covariates both in the ANCOVA and linear regression models. A higher percentage of boys met the WHO PA recommendations compared to girls (69.6% vs. 40.9%, respectively; p < 0.001). There was a negative association between MVPA and subtotal fat and abdominal fat in both girls and boys. After adjusting for perinatal and lifestyle variables, we found that subtotal body fat, abdominal fat, and fat mass index (FMI) were significantly lower in those classified as active. MVPA was associated with body fat both in boys and girls. More research is needed to identify the cutoffs points of MVPA that generate benefit to boys and girls in all body composition components.

Neural stem/progenitor cells (NSPC) are multipotent cells that renew themselves and could differentiate into neurons and macro glia (astrocytes and oligodendrocytes) of the nervous system during embryonic development. Duchenne muscular dystrophy is a severe type of muscular dystrophy caused by mutations in the dmd gene, and one-third of patients cursed with neuro-cognitive impairments. In this data article, we take advantage of the differentiation capacity of NSPC as a model to increase our knowledge in the neuronal and/or astrocytic differentiation and to evaluate the expression of dystrophins and dystrophin-associated proteins. We showed the characterization of undifferentiated and neuron and/or astrocyte differentiated NSPC. In addition, we evaluated the expression and subcellular localization of dystrophins and β-dystroglycan in undifferentiated NSPC and differentiated to neurons and astrocytes.•Primary culture of NSPC was characterized by the expression of multipotent markers nestin and Sox2.•Neuronal or astrocytic differentiation of NSPC was performed by basic fibroblast growth factor (FGF2) withdrawal, histamine or ciliary neurotrophic factor (CNTF) treatment, and expression of βIII-tubulin or glial fibrillary acidic protein (GFAP) as differentiation markers for neurons or astrocytes was evaluated.•This study will contribute to the understanding of dystrophins and dystrophin-associated proteins expression and function during neuronal or astrocytic differentiation of NSPC., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier B.V.)

The pheromone response and the high osmolarity glycerol (HOG) pathways are considered the prototypical MAPK signaling systems. They are the best-understood pathways in eukaryotic cells, yet they continue to provide insights in how cells relate with the environment. These systems are subjected to tight regulatory circuits to prevent hyperactivation in length and intensity. Failure to do this may be a matter of life or death specially for unicellular organisms such as Saccharomyces cerevisiae. The signaling pathways are fine-tuned by positive and negative feedback loops exerted by pivotal control elements that allow precise responses to specific stimuli, despite the fact that some elements of the systems are common to different signaling pathways. Here we describe the experimentally proven negative feedback loops that modulate the pheromone response and the HOG pathways. As described in this review, MAP kinases are central mechanistic components of these feedback loops. They have the capacity to modulate basal signaling activity, a fast extranuclear response, and a longer-lasting transcriptional process.

Duchenne muscular dystrophy (DMD) is a genetic disease caused by mutations in the dystrophin gene. Dystrophin is required for the organization of a complex consisting of dystroglycans, sarcoglycans, dystrobrevins and syntrophins, known as the dystrophin-associated proteins complex (DAPC). In addition to muscle degeneration, cognitive impairment has been reported in DMD patients. To characterize a suitable model for studying the embryonic cerebral functions of dystrophin, we analyzed the expression patterns of dystrophins/DAPC in undifferentiated and differentiated embryonic neural stem/progenitor cells (NSPC). We found that NSPC express mRNAs for dystrophins Dp427, Dp140, Dp71 and Dp40; β-dystroglycan; α- and β-dystrobrevin; α1-, β1-, β2- and γ2-syntrophin; and β-, γ-, δ- and ε-sarcoglycan. Some of these were differentially regulated during neuronal or astrocytic differentiation. Interestingly, the protein expression levels of Dp140, β-dystroglycan and α2-dystrobrevin were also differentially regulated. Additionally, we found that proliferating NSPC and differentiated neurons and astrocytes show immuno-positive staining for dystrophins and β-dystroglycan. Our results show that dystrophins and DAPC components are expressed and regulated during the neuronal or astrocytic differentiation of NSPC, suggesting that these proteins may have different roles in the brain development., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Bone health problems may be related to the nutritional deficit in pediatric patients with cerebral palsy. It is common to find asymptomatic vertebral fractures when they have low bone mineral density. Fat mass deficit could be related to a lower bone mineral density and a higher risk of vertebral fractures., Objectives: To study the bone health of patients with CP and its relationship with neurological and nutritional status., Purpose: Cerebral palsy (CP) is the most common cause of motor disability in pediatric age., Methods: Cross-sectional, observational, descriptive, and analytical study in which patients with CP between 4 and 5 years with Gross Motor Function Classification System (GMFCS) grades III-IV-V were included. It was carried out: survey, anthropometric study, bioimpedanciometry (BIA), and bone densitometry. Patients with low bone mineral density (BMD Z score less than - 2.0) underwent lumbar radiography looking for vertebral fractures to be diagnosed with osteoporosis., Results: Total sample: 51 patients (51.0% women). Mean age: 11.0 ± 0.5 years. BMD Z score average: - 2.1 (95% CI - 2.5, - 1.7). BMD Z score according to GMFCS: grade III - 1.6 (- 2.2; - 1.), grade IV - 1.6 (- 2.4; - 0.9), grade V - 3.1 (- 3.9, - 2.2) (p = 0.013). Bone health classification according to the International Society for Clinical Densitometry was: 47.1% normal, 52.9% low BMD. Relationship between low BMD and low fat mass (p = 0.030) and low cell mass (p = 0.040) was found. Prevalence of vertebral fractures in lumbar radiography: 25.9%, increasing as the degree of neurological involvement. Vertebral fractures were found in 5/13 GMFCS grade V, 2/6 GMFCS grade IV, and 0/10 GMFCS grade III., Conclusions: Bone health in the pediatric population with CP is compromised in relation to the degree of neurological involvement and nutritional status. Those patients with moderate-severe cerebral palsy and low BMD seem to present an increased risk of fracture.

Background: The EQ-5D-5 L is a quality-of-life questionnaire based on individuals' preferences that is widely employed for cost-effectiveness analysis. Given the current demand for mapping algorithms to directly assign "utilities", this study aimed to generate different mapping models for predicting EQ-5D-5 L utility values based on scores of the Oxford Hip Score (OHS) and Oxford Knee Score (OKS) questionnaires provided by patients suffering from hip and knee osteoarthritis (OA), respectively, and to assess the predictive capability of these functions., Methods: This was a prospective, observational study. Following the criteria of the American Rheumatism Association, 361 patients with hip OA and 397 with knee OA from three regions in Spain were included. Health-related quality of life (HRQoL) was assessed through the EQ-5D-5 L general questionnaire and the OHS and OKS specifically for lower limb OA. Based on the scores on the OHS and OKS questionnaires, EQ-5D-5 L utilities were estimated using 4 models: ordinary least squares (OLS), Tobit, generalized linear model (GLM), and beta regression (Breg). The models were validated on the same patients after 6 months: the mean absolute error (MAE) and mean squared error (MSE) with their 95% confidence intervals (CI), mean values of standard errors (SE), intraclass correlation coefficients (ICC), and Bland-Altman plots were obtained., Results: The lowest MAEs were obtained using GLM and Breg models, with values of 0.1103 (0.0993-0.1214) and 0.1229 (0.1102-0.1335) for hip OA, and values of 0.1127 (0.1014-0.1239) and 0.1141 (0.1031-0.1251) for knee OA. MSE values were also lower using GLM and Breg. ICCs between predicted and observed values were around or over the 0.8 cut-off point. Bland-Altman plots showed an acceptable correlation, but precision was lower for subjects with worse HRQoL, which was also evident when comparing MAEs of the bottom and top halves of the utilities scale. Predictive equations for utilities based on OHS/OKS scores were proposed., Conclusions: The OHS and OKS scores allow for estimating EQ-5D-5 L utility indexes for patients with hip and knee OA, respectively, with adequate validity and precision. GLM and Breg produce the best predictions. The predictive power of proposed equations is more consistent for subjects in better health condition.

Introduction: Cerebral palsy (CP) is the most frequent cause of motor disability in the paediatric age. The aim of this article is the study of the nutritional status of patients with CP followed-up in a reference hospital, as well as the relationship between neurological and nutritional state., Material and Methods: A cross-sectional, observational, descriptive and analytical study was conducted on a sample consisting of 4-15years old patients with CP with Gross Motor Function Classification System (GMFCS) gradesIII-IV-V, from a specialised paediatric hospital reference area. An interview (collection of general data, medications and nutritional habits), anthropometric study and bioimpedance (BIA) measurements were carried out., Results: The study included 69 patients (recruitment 84.15%), with a mean age of 10.46±0.43years, and 50.7% females. The distribution according to GMFCS scale was: gradeIII (36.2%), gradeIV (29%), and gradeV (34.8%). According to weight for height: moderate malnutrition 21.8% (gradeV: 33.3%), severe malnutrition 5.8% (gradeV: 12.6%), overweight/obesity 23.2% (gradeIII: 24%, gradeIV: 35%). Adequate level of lean mass for height: gradeIII (36%), gradeIV (55%), and gradeV (16.7%). Fat excess: gradeIII (36%), gradeIV (40%), and gradeV (29.2%). Fat mass comparison: BIA 6.89±0.64kg versus anthropometry 5.56±4.43kg., Conclusions: In CP grade GMFCSV, the weight deficit associated with a decrease in lean body mass is common. Patients with CP grades GMFCSIII-IV have a significant prevalence of overweight/obesity. Anthropometry is a useful tool for nutritional assessment in children with CP, although fat levels could be underestimated., (Copyright © 2019. Publicado por Elsevier España, S.L.U.)

Physical activity (PA) and exercise improve the overall quality of life, as well as prevent the onset of diseases in healthy children and adolescents, and as an aid to treat prevalent chronic diseases in childhood. PA and exercise are like medicine, but sedentary lifestyle and inactivity cause disease. In this article, the existing scientific evidence in this field is reviewed and recommendations for professionals involved in child health are updated. A good knowledge of how to prescribe exercise and PA in paediatrics in different diseases is necessary. Interventions to avoid inactivity of children and adolescents must be supported by the appropriate increase in the level of PA, through integration and training programs, which achieve both an overall improvement of the neuromuscular physical condition and also physical, cognitive, and psychosocial performance. The Health Promotion Committee of Spanish Paediatric Association proposes strategies that help to obtain this objective, aiming to improve the health of our patients through the practice of exercise and the increase in PA., (Copyright © 2020 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: Osteoarthritis of the lower limb (OALL) worsens health-related quality of life (HRQL), but this impact has not been quantified with standardized measures. We intend to evaluate the impact of OALL on HRQL through measures based on individual preferences in comparison to the general population., Methods: A cross-sectional study was designed. A total of 6234 subjects aged 50 years or older without OALL were selected from the Spanish general population (National Health Survey 2011-12). An opportunistic sample of patients aged 50 years or older diagnosed with hip (n = 331) or knee osteoarthritis (n = 393), using the American Rheumatism Association criteria, was recruited from six hospitals and 21 primary care centers in Vizcaya, Madrid and Tenerife between January and December 2015. HRQL was measured with the EQ-5D-5L, and the results were transformed into utility scores. Sociodemographic variables (age, sex, social group, cohabitation), number of chronic diseases, and body mass index were considered. The clinical stage of OALL was collected using the Western Ontario and McMaster Universities Osteoarthritis Index and the Oxford hip score and Oxford knee score. Generalized linear models were constructed using the utility index as the dependent variable., Results: HRQL expressed by OALL patients was significantly worse than this of the general population. After adjustment for sociodemographic and clinical characteristics, the mean utility loss was -0.347 (95% CI: -0.390, -0.303) for osteoarthritis of the hip and -0.295 (95% CI: -0.336, -0.255) for osteoarthritis of the knee. OALL patients who were treated at a hospital had an additional utility loss of -0.112 (95% CI: -0.158, -0.065)., Conclusion: OALL has a great impact on HRQL. People with OALL perceive a utility loss of approximately 0.3 points compared to the general population without osteoarthritis, which is very high in relation to the utility loss reported for other chronic diseases and for arthritis in general., Competing Interests: The authors have declared that no competing interests exist.

Objective: to analyse the characteristics of primary care nurse consultation and to identify the factors associated with different types of activity., Method: A cross-sectional multicentre observational study in 23 health centres (Community of Madrid), on 164 different nurses. The consultation was classified according to a consensus proposal in: "preventive activities" (PA), "self-care deficit" (SD), "coping and adaptation" (CA) and "diagnostic and therapeutic procedures" (DTP). Sociodemographic characteristics, health needs, and consultation characteristics were collected. A bivariate inferential analysis was made, and explanatory multivariate models were constructed., Results: Of the total consultations 63.6% (95% CI: 59.9-67.3%) were classified as DTP. The consultation was directly requested by the patient in 24.3% (95% CI: 21.0- 27.7%) of the cases. There were no differences in the type of consultations by gender (P=.858), or for immigrants (P=.428). Subjects from higher social classes more frequently attended PA consultations (P=.007). There were no other differences in accessibility. The DTP consultations related to previous hospitalizations (OR: 1.191, 95% CI: 1.088-1.304), or the previous use of services (nurse consultation OR: 1.002, 95% CI: 1.000-1.003, medical consultation OR: 1.003, 95% CI: 1.000-1.006)., Conclusions: The nurse consultation is mainly aimed at carrying out procedures and previously arranged consultation prevails over patient demanded consultation. No inequities in accessibility were detected, but the type of care for different social groups was not homogeneous., (Copyright © 2018 Elsevier España, S.L.U. All rights reserved.)

Introduction: The low FODMAP diet (fermentable oligosaccharides, monosaccharides, disaccharides, and polyols) has shown to be effective in adult patients with irritable bowel syndrome, but there are few studies on paediatric patients. The aim of this study is to assess the implementation and the outcomes of a low FODMAP diet in the treatment of functional abdominal pain in children from a Mediterranean area., Material and Methods: A table was designed in which foods were classified according to their FODMAP content, as well as a 'Symptoms and Stools Diary'. A prospective study was conducted on children with functional abdominal pain in our Paediatric Gastroenterology Unit., Results: A total of 22 patients were enrolled in the trial, and 20 completed it. Data were collected of the abdominal pain features over a period of 3 days, and then patients followed a two-week low FODMAP diet. Afterwards, information about abdominal pain features was collected again. After the diet, they showed fewer daily abdominal pain episodes compared to baseline (1.16 [IQR: 0.41-3.33] versus 2 [IQR: 1.33-6.33] daily episodes, P=.024), less pain severity compared to baseline (1.41cm [IQR: 0.32-5.23] versus 4.63cm [IQR: 2.51-6.39] measured by 10-cm Visual Analogue Scale, P=.035), less interference with daily activities, and less gastrointestinal symptoms. Only 15% of patients found it difficult to follow the diet., Conclusions: The implementation of a low FODMAP diet for 2 weeks in a Mediterranean paediatric population diagnosed with functional abdominal pain is possible with adapted diets. It was highly valued by patients, and they showed an improvement in abdominal pain symptoms assessed by objective methods., (Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Somatic cell reprogramming is a biphasic phenomenon that goes through a mesenchymal-to-epithelial transition, called initiation phase, followed by a maturation phase wherein reprogramming cells acquire pluripotency. Here, we show that these phases display a differential response to Wnt signaling activation. Wnt signaling increases colony formation by promoting cellular epithelialization during the initiation phase in a TCF7-dependent manner. However, during maturation phase, it is also responsible for inducing mesendodermal differentiation, which is negatively regulated by TCF7L1. Thus, Wnt signaling inhibition or TCF7L1 overexpression downregulates mesendodermal gene expression without perturbing pluripotency. Together, our results demonstrate that a phase-specific modulation of Wnt signaling leads to an improved reprogramming efficiency in terms of colony output and pluripotency acquisition. This work provides new insights into the cell context-dependent roles of Wnt signaling during human somatic cell reprogramming. Stem Cells 2018;36:683-695., (© AlphaMed Press 2018.)

Background: the main action of vitamin D is to maintain the concentration of calcium and phosphorus within the physiological range, allowing normal metabolism and bone mineralization. Vitamin D receptors have recently been described in many tissues, therefore vitamin D deficiency has been related not only to rickets, but also to increased risk of diabetes, obesity, cardiovascular, oncological, infectious and autoimmune diseases., Objective: the aim of the study was to know the vitamin D concentration in a healthy pediatric population and to verify its influential factors, as well as to analyze the current situation of vitamin D prophylaxis and to evaluate the effectiveness of current recommendations., Methods: one hundred and seven healthy patients aged between one and 15 years were selected, who required a blood test as a preoperative minor surgery and whose pathology did not influence the parameters of the study., Results: the sample analyzed had a total of 78.5% males and a mean age of 7.17 ± 3.79 years. Mean values of vitamin D were 26.07 ± 7.11 ng/ml; up to 72.9% had insufficient levels. The sample was divided into two groups: patients with hypovitaminosis D and patients with optimal vitamin D levels. A predominance of males with a higher body mass index, from immigrant parents, and the presence of extreme phototypes were observed in the hypovitaminosis group. There was also a higher risk of hypovitaminosis in those who had not performed prophylaxis during the first year of life., Conclusions: the high percentage of healthy children with vitamin D deficiency is evident, and current recommendations for prophylaxis are not carried out by the population as recommended by current guidelines.

Background: Significant efforts have been made to improve the nutritional support of very preterm infants. Large surveys may help to know the nutritional practices for preterm infants in neonatal units and identify if they are in line with the current guidelines., Methods: A multicentre nationwide web-based survey on clinical feeding practices in very low birth weight (VLBW) infants was conducted in tertiary neonatal hospitals that admit infants with a birth weight < 1,500 g and/or a gestational age of < 32 weeks., Results: The questionnaire was completed by 53 units (response rate, 59%). Over 90% of the units surveyed start amino-acid administration immediately after birth and more than half use novel intravenous fish oil-based lipid emulsions. Enteral nutrition is started within 24 hours of birth in 65% of units and 86% of these are medium-sized or large. Feeding volumes are increased at a rate of 10-30 ml/kg/day in > 90% of units. Monitoring of serum phosphorus was measured more frequently than albumin (p = 0.009) or triglycerides (p = 0.037), but only 28% of centres regularly measure pre-albumin as a nutritional biomarker. Human milk fortification and iron supplementation, starting at four weeks of age, are almost universal. However, only 30% of units administer 800 IU/day of vitamin D. Nearly 50% of the units discharge infants on preterm formula., Conclusion: Most Spanish neonatology units use early amino-acid supplementation and over half use novel fish oil-based lipid emulsions. Post-discharge nutrition practices and vitamin administration vary greatly.

Background: Cancer is a growing problem in persons living with HIV infection (PLWH) and hepatitis C virus (HCV) coinfection could play an additional role in carcinogenesis. Herein, all cancers in an HIV-mono and HIV/HCV-coinfected cohort were evaluated and compared to identify any differences between these two populations., Methods: A retrospective cohort study was conducted including all cancers in PLWH between 1993 and 2014. Cancers were classified in two groups: AIDS-defining cancer (ADC) and non-AIDS-defining cancer (NADC). Cancer incidence rates were calculated and compared with that observed in the Spanish general population (GLOBOCAN, 2012), computing the standardized incidence ratios (SIRs). A competing risk approach was used to estimate the probability of cancer after HIV diagnosis. Cumulative incidence in HIV-monoinfected and HIV/HCV-coinfected patients was also compared using multivariable analysis., Results: A total of 185 patients (117 HIV-monoinfected and 68 HIV/HCV) developed cancer in the 26 580 patient-years cohort, with an incidence rate of 696 cancers per 100 000 person-years, higher than in the general population (SIR = 3.8). The incidence rate of NADC in HIV/HCV-coinfected patients was 415.0 (SIR = 3.4), significantly higher than in monoinfected (377.3; SIR = 1.8). After adjustments, HIV/HCV-coinfected patients had a higher cumulative incidence of NADC than HIV-monoinfected (adjusted hazard ratio = 1.80), even when excluding hepatocellular carcinomas (adjusted hazard ratio = 1.26)., Conclusion: PLWH have a higher incidence of NADC than the general population and HCV-coinfection is associated with a higher incidence of NADC. These data justify the need for prevention strategies in these two populations and the importance of eradicating HCV.

Objectives: The aim of the present study was to assess reproducibility and inter-rater reliability of 2 nutritional screening tools (NST): Screening Tool for Risk on Nutritional Status and Growth (STRONGkids) and Screening Tool for the Assessment of Malnutrition in Paediatrics (STAMP)., Methods: Prospective observational multicentre study. Patients ages 1 month or older admitted to paediatric or surgical wards were tested within 24 hours of admission by 2 independent observers: experts specialized in paediatric nutrition (physicians or dieticians) and clinical staff nonexpert in nutrition. Diagnosis on admission, underlying diseases, and length of stay were registered., Statistical Analysis: Kappa index (κ) to evaluate agreement between observers., Results: A total of 223 patients were included (53.4% boys), with mean age of 5.59 (95% confidence interval 4.94-6.22) years. Experts classified 9.9% of patients at high risk with STRONGkids and 19.7% using STAMP, whereas nonexpert staff assigned 6.7% of patients to the high-risk category with STRONGkids and 21.9% with STAMP. Agreement between expert and nonexpert staff was good: 94.78% for STRONGkids (κ 0.72 [P < 0.001]); 92.55% for STAMP (κ 0.74 [P < 0.001]). The rate of malnutrition was significantly higher among high-risk patients with both NST, independent of examiner experience. After adjusting for age, both STRONGkids and STAMP high-risk scores predicted longer length of stay, whether assessed by experts or nonexperts, although differences were higher with STRONGkids., Conclusions: Agreement between experts and nonexpert staff in nutrition was good, producing a similar high-risk patient profile. Our results demonstrate that these NSTs are appropriate for nutritional screening in settings in which users have no previous experience in the field.

Background: New patterns in epidemiological characteristics of people living with HIV infection (PLWH) and the introduction of Highly Active Antiretroviral Therapy (HAART) have changed the profile of hospital admissions in this population. The aim of this study was to evaluate trends in hospital admissions, re-admissions, and mortality rates in HIV patients and to analyze the role of HCV co-infection., Methods: A retrospective cohort study conducted on all hospital admissions of HIV patients between 1993 and 2013. The study time was divided in two periods (1993-2002 and 2003-2013) to be compared by conducting a comparative cross-sectional analysis., Results: A total of 22,901 patient-years were included in the analysis, with 6917 hospital admissions, corresponding to 1937 subjects (75% male, mean age 36±11 years, 37% HIV/HCV co-infected patients). The median length of hospital stay was 8 days (5-16), and the 30-day hospital re-admission rate was 20.1%. A significant decrease in hospital admissions related with infectious and psychiatric diseases was observed in the last period (2003-2013), but there was an increase in those related with malignancies, cardiovascular, gastrointestinal, and chronic respiratory diseases. In-hospital mortality remained high (6.8% in the first period vs. 6.3% in the second one), with a progressive increase of non-AIDS-defining illness deaths (37.9% vs. 68.3%, P<.001). The admission rate significantly dropped after 1996 (4.9% yearly), but it was less pronounced in HCV co-infected patients (1.7% yearly)., Conclusions: Hospital admissions due to infectious and psychiatric disorders have decreased, with a significant increase in non-AIDS-defining malignancies, cardiovascular, and chronic respiratory diseases. In-hospital mortality is currently still high, but mainly because of non-AIDS-defining illnesses. HCV co-infection increased the hospital stay and re-admissions during the study period., (Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

PC12 cells acquire a neuronal phenotype in response to nerve growth factor (NGF). However, this phenotype is more efficiently achieved when the Dp71Δ78-79 dystrophin mutant is stably expressed in PC12-C11 cells. To investigate the effect of Dp71Δ78-79 overexpression on the protein profile of PC12-C11 cells, we compared the expression profiles of undifferentiated and NGF-differentiated PC12-C11 and PC12 cells by 2DE. In undifferentiated cultures, one protein was downregulated, and five were upregulated. Dp71Δ78-79 overexpression had a greater effect on differentiated cultures, with ten proteins downregulated and seven upregulated. The protein with the highest upregulation was HspB1. Changes in HspB1 expression were validated by Western blot and immunofluorescence analyses. Interestingly, the neurite outgrowth in PC12-C11 cells was affected by a polyclonal antibody against HspB1, and the level of HspB1 and HspB1Ser86 decreased, suggesting an important role for this protein in this cellular process. Our results show that Dp71Δ78-79 affects the expression level of some proteins and that the stimulated neurite outgrowth produced by this mutant is mainly through upregulation and phosphorylation of HspB1., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objectives: This study aims to assess the psychometric properties of two measurement tools for patient satisfaction with nursing care in Primary Care, the satisfaction level, and the personal and consultation characteristics associated with its variability., Methods: Subjects randomly selected in 23 Health Care centres in the Community of Madrid were included. Satisfaction was measured by means of the AMABLE and Baker questionnaires, in which the psychometric properties were evaluated. Sociodemographic characteristics of the consultations, variables related to health status, and other related to the consultation process were collected. An explanatory model using Generalized Estimating Equations was constructed., Results: The 662 subjects expressed a mean satisfaction of 4.95/5 (SD .25) with AMABLE, and 4.83/5 (SD .42) with the Baker questionnaire. AMABLE had a single dimension (Cronbach's alpha .85), and Baker three: professional care (mean 4.76, SD .48 Cronbach's alpha .74), depth of relationship (mean 3.76, SD 1.18, Cronbach's alpha .73), and perceived time (mean 4.42, SD .86, Cronbach's alpha .47). Ageing, a better perception of health status, and appointments arranged by nurses were associated with higher expressed satisfaction. Home care, hospital admissions, delayed consultation, extended family, or high family income were associated with lower satisfaction., Conclusions: Satisfaction with nurse consultations in Primary Care was very high, and varied depending on personal characteristics and on the type of consultation. The assessed tools allowed this outcome to be measured properly., (Copyright © 2014 SECA. Published by Elsevier Espana. All rights reserved.)

Clinical practice guidelines are an important tool for improving healthcare. In recent years there has been accumulating evidence on the impact of nutritional supplementation with probiotics in the very low birth weight infants. With no uniformity in microorganisms and strains used. The Spanish Neonatology Society (SENeo), through its Nutrition and Metabolism Group has undertaken to develop recommendations that will be useful as a guide for the neonatologist in this field., (Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.)

Objective: To identify socio-cultural, obstetric and perinatal characteristics associated with complete breastfeeding (CBF) during the first 4 months of age, depending on maternal origin., Material and Methods: Socio-cultural, obstetric and perinatal aspects associated with breastfeeding depending on maternal origin were evaluated in a longitudinal study in a representative infant population from Aragon (n = 1452)., Results: The prevalence of CBF was higher in immigrant mothers than in those from Spain. CBF was maintained in 37.2% of mothers from Spain at 4 months, compared with 43% of immigrants (P=.039) (RR Spanish/immigrants=0.76; 95% CI: 0.58-0.99); at 6 months this occurred in 13.9% vs. 23.8%, respectively (P<.001) (RR Spanish/immigrants=0.52; 95% CI: 0.37-0.72). The factors associated with CBF at 4 months are different between both groups. Mothers born in Spain are older (P=.002), have higher academic level (P=.001), greater parity (P=.003), and a higher probability of vaginal delivery (P=.005); and their children have the highest anthropometric values at birth. However, in immigrant mothers, the maintenance of CBF was associated with a higher maternal body mass index and with working at home. In both groups, CBF remains more frequently in those mothers who do not smoke (P=.001)., Conclusions: The prevalence of CBF during the first months of life is higher in immigrant mothers than in those from Spain, and socio-cultural, obstetric and perinatal factors are different, depending on maternal origin., (Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.)

Objectives: To study the current prevalence of breastfeeding (BF) in Aragon (Spain) during the first 12 months of life, and analyse its demographic, perinatal and social influential factors., Material and Methods: Obstetric, perinatal and feeding aspects were evaluated in a longitudinal and observational study, in a representative cohort of infant population from Aragon born between March 2009 to March 2010, controlled until 12 months of age (N=1.602)., Results: Exclusive or predominant BF was more frequent than the rest of feeding modalities during the first 4 months of life. Maintenance prevalence of any BF modality was 82.5% at 1(st) month of age, 71.8% at 3(rd), 54.3% at 6(th), and 27.8% at 12 months of age. Maternal variables that were significantly associated with BF maintenance both at 1 and 6 months of age were: delivery modality (higher probability in case of vaginal delivery), academic level (higher probability if university studies), origin (higher probability in mothers from Africa), adiposity (higher probability of normal weight or overweight mothers compared with obese ones), and not to smoke during gestation., Conclusions: BF prevalence in Aragon (Spain) during the first 12 months of age is high and has increased compared with previous data. BF continues in more than half of infants at six months and in a quarter of infants at 12 months of age. Maternal factors that significantly influence BF initiation and maintenance are, delivery modality, academic level, origin (immigration), adiposity and smoking habit., (Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.)

Objective: To check whether secular changes exist in growth pattern of caucasic children from the North of Spain up to 2 years of age compared with 25-30 years ago population growth curves., Material and Methods: Longitudinal study of a representative cohort of caucasic infants born a term in Aragon (n=1.099). Standard deviation scores (z-scores) for weight, length and body mass index (BMI) have been calculated by two available 25-30 years ago population growth curves (Sobradillo et al. and Ferrández et al.)., Results: At all ages, weight, length and BMI mean z-scores significantly vary depending on the growth standard curve used (p≤0.001). At birth, weight z-score is -0.36 (95%CI:-0.42;-0.30) according to Sobradillo et al. and -0.26 (95%CI:-0.29;0.33) according to Ferrández et al. These differences decreased progressively becoming minimum at 2 years (mean weight z-score -0.08 and -0.05; respectively). At this age, length mean z-score is +0.54 (95%CI:0.48;0.61) according to Sobradillo et al. and +0.19 (95%CI:0.12;0.25) according to Ferrández et al. Mean BMI z-scores of our sample showed lower values than selected standards., Conclusions: Current birth weight of caucasic infants from Northern Spain is lower than in the previous generation. At 2 years of age there is a trend of increasing length, with a similar weight, resulting in lower BMI values., (Copyright AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.)

Background: Different conditions in health services utilization may create situations of inequity. The objective was analyze the differences of nurse consultation utilization in primary care., Methods: Cross-sectional study, in 23 health centres in Madrid. Environmental variables, consultation characteristics, socio-demographic and health need characteristics were collected. The quality of life and satisfaction were also studied. The variables were classified according to the "behavioral model" in predisposing, enabling or need variables. Explanatory multivariate models were constructed (Generalized-Estimating-Equations)., Results: The higher income areas and aging, predisposing factors, were associated with increases of 17% (95% CI: 0.4 to 36.9%) and 11.0% per decade (95% CI: 6.2 - 16.2) in nursing consultations per year. Among enabling factors, each additional minute of consultation length was associated with an increase of 2.0% (95% CI :1.2-2, 9%) in number of nurse consultations, each new medical consultation was associated with a increase of 2.7% (95% CI: 2.1-3.2%) and the delay in getting appointment over a day, represented a decrease of 32.8% (95% CI: 19.3 to 44.1%) in the total nursing consultations. Each chronic condition, which expresses the need health, was associated with an increase in the number of visits of 4.8% (95% CI: 1.7 to 8.0%). The improved perception of quality of life was associated with a reduction of 5.4% (95% CI 1.0 to 8.7%) of the consultations., Conclusion: The difference of the use of primary care nurse consultations is based on health need criteria, but is also influenced by accessibility conditions.

Background: Identifying the economic value assigned by users to a particular health service is of principal interest in planning the service. The aim of this study was to evaluate the perception of economic value of nursing consultation in primary care (PC) by its users., Methods and Results: Economic study using contingent valuation methodology. A total of 662 users of nursing consultation from 23 health centers were included. Data on demographic and socioeconomic characteristics, health needs, pattern of usage, and satisfaction with provided service were compiled. The validity of the response was evaluated by an explanatory mixed-effects multilevel model in order to assess the factors associated with the response according to the welfare theory. Response reliability was also evaluated. Subjects included in the study indicated an average Willingness to Pay (WTP) of €14.4 (CI 95%: €13.2-15.5; median €10) and an average Willingness to Accept [Compensation] (WTA) of €20.9 (CI 95%: €19.6-22.2; median €20). Average area income, personal income, consultation duration, home visit, and education level correlated with greater WTP. Women and older subjects showed lower WTP. Fixed parameters explained 8.41% of the residual variability, and response clustering in different health centers explained 4-6% of the total variability. The influence of income on WTP was different in each center. The responses for WTP and WTA in a subgroup of subjects were consistent when reassessed after 2 weeks (intraclass correlation coefficients 0.952 and 0.893, respectively)., Conclusions: The economic value of nursing services provided within PC in a public health system is clearly perceived by its user. The perception of this value is influenced by socioeconomic and demographic characteristics of the subjects and their environment, and by the unique characteristics of the evaluated service. The method of contingent valuation is useful for making explicit this perception of value of health services.

Introduction: The development of malignancies is a problem associated with HIV infection. The incidence and spectrum of malignancies has been modified with the addition of highly active antiretroviral therapy (HAART)., Aim: To describe the clinical and epidemiological characteristics and prognosis of HIV patients who have developed a malignancy., Methods: Retrospective observational study was conducted in HIV + patients who developed a malignancy between 1993-2010 in a referral hospital. AIDS-defining malignancies (ADN) and non-AIDS-defining malignancies (NADN) were compared., Results: 125 patients were identified with at least one malignancy. The most frequent malignancies were: non-Hodgkin lymphoma (n; 39; 30.2%), Kaposi's sarcoma (n: 20; 15.5%), Hodgkin's disease (n: 11; 8.8%), lung cancer (n: 20; 15.5%) and hepatocellular carcinoma (n: 9; 6.9 %). The mean age was 42 ± 11 years, 84% male, 55.8% were coinfected with HBV and or HCV. The risk behaviors were: 45.6% intravenous drug users, 16.8% men who have sex with men and 20% heterosexuals). There were 67 (52%) NADN and 62 (48%) ADN; NADN patients had a longer story of HIV infection and longer exposure to HAART, better level of immunodeficiency and better virological control than ADN patients. Four patients developed a second malignancy. Overall survival was 34.7%., Conclusions: We found an increased incidence of NADN, appearing in patients with better virological and immunological control than ADN group. Mortality of patients with HIV infection and malignancy is still very high.

Background: During rat development, histamine (HA) is one of the first neuroactive molecules to appear in the brain, reaching its maximal value at embryonic day 14, a period when neurogenesis of deep layers is occurring in the cerebral cortex, suggesting a role of this amine in neuronal specification. We previously reported, using high-density cerebrocortical neural precursor cultures, that micromolar HA enhanced the effect of fibroblast growth factor (FGF)-2 on proliferation, and that HA increased neuronal differentiation, due to HA type 1 receptor (H(1)R) activation., Results: Clonal experiments performed here showed that HA decreased colony size and caused a significant increase in the percentage of clones containing mature neurons through H(1)R stimulation. In proliferating precursors, we studied whether HA activates G protein-coupled receptors linked to intracellular calcium increases. Neural cells presented an increase in cytoplasmic calcium even in the absence of extracellular calcium, a response mediated by H(1)R. Since FGF receptors (FGFRs) are known to be key players in cell proliferation and differentiation, we determined whether HA modifies the expression of FGFRs1-4 by using RT-PCR. An important transcriptional increase in FGFR1 was elicited after H(1)R activation. We also tested whether HA promotes differentiation specifically to neurons with molecular markers of different cortical layers by immunocytochemistry. HA caused significant increases in cells expressing the deep layer neuronal marker FOXP2; this induction of FOXP2-positive neurons elicited by HA was blocked by the H(1)R antagonist chlorpheniramine in vitro. Finally, we found a notable decrease in FOXP2+ cortical neurons in vivo, when chlorpheniramine was infused in the cerebral ventricles through intrauterine injection., Conclusion: These results show that HA, by activating H(1)R, has a neurogenic effect in clonal conditions and suggest that intracellular calcium elevation and transcriptional up-regulation of FGFR1 participate in HA-induced neuronal differentiation to FOXP2 cells in vitro; furthermore, H(1)R blockade in vivo resulted in decreased cortical FOXP2+ neurons.

Introduction: Being born small for gestational age (SGA) has short and long term risks. The aim of this study was to describe perinatal and socio-cultural characteristics, and the pattern of growth and diet of SGA infants during their first 6 months of life., Materials and Methods: Anthropometry and diet were evaluated during six months in a representative sample of 1596 newborns the population of Aragon (Spain)., Results: Mothers of SGA (N=94) infants gained less weight during pregnancy (10.5±5.8 vs 12.0±5.07 kg, P=.012), gestational age at birth was lower (37.84±1.7 vs 39.06±1.6 weeks, P<.001), and the probability of cesarean delivery was higher (37.2% vs 20.5%, P=.001). The height of the mother was lower in the SGA group (1.61±0.58 vs 1.63±0.06 metres, P=.004), but their body mass index was similar. No differences were found between groups in social or cultural aspects. Mothers of SGA infants smoked more during pregnancy (32.3% vs 18.5%, P=.003) (RR = 1.92; 95% CI; 1.31 to 3.02). Infants born SGA remained smaller during the first 6 months of life, and the monthly weight gain was similar to the rest. In the SGA group, the prevalence of breastfeeding was lower at 4 months of age (54.9% vs 68.2%, RR = 0.58, 95% CI; 0.38 to 0.89)., Conclusions: Infants born SGA are more likely to converge a number of characteristics that must be considered together because they may lead to health risks. SGA do not show a rapid recovery pattern of postnatal growth, and their smaller size persists at six months., (Copyright © 2011 Asociación Española de Pediatría. Published by Elsevier España. All rights reserved.)

Transforming Growth Factor-β (TGF-β) family members are ubiquitously expressed, participating in the regulation of many processes in different cell types both in embryonic and adult stages. Several members of this family, including Activins, TGF-β1-3 and Nodal, have been implicated in the development and maintenance of various organs, in which stem cells play important roles. Although TGF-β was initially considered an injury-related cytokine, it became clear that not only TGF-β, but other members of this family, play critical roles in morphogenesis and cell lineage specification. During brain development, Activin and TGF-βs as well as their cognate receptors, are expressed in different patterns. The roles of Activin and TGF-β during CNS development are sometimes contradictory, because these proteins present different actions depending on the cell type and the context. The aim of this review is to summarize current information on the actions of TGF-β members during developing brain, and also on Neural Stem/Progenitor Cells (NSPC). We focus on the TGF-β subgroup, specifically on the effects of TGF-β1 and Activin A. In the first section we describe the main characteristics of the ligands, its receptors as well as the proteins and mechanisms involved in signaling. Next, we discuss the main advances concerning TGF-β1 and Activin actions during brain development and their roles in NSPC fate decision and neuroprotection both in vitro and in vivo. The emerging picture from these studies suggests that these growth factors can be used to manipulate neurogenesis and might help to achieve restoration after brain deterioration.

Background: Malnutrition among hospitalized patients has clinical implications, and interest has arisen to find screening tools able to identify subjects under risk. At present, there is no consensus about the most suitable nutrition screening tool for pediatric patients., Aim: To validate STAMP (Screening Tool for the Assessment of Malnutrition in Pediatrics) pediatric screening tool in Spain., Methods: Descriptive cross-sectional study of patients admitted to a 3rd level children's hospital with both medical and surgical specialities. During the first 24 hours of admission, STAMP screening tool was applied. For its validation, results were compared with those obtained from a nutritional assessment performed by specialist staff, which included clinical, anthropometric and body composition data., Results: A sample of 250 children was studied. Nutritional assessment identified 64 patients (25.6%) under risk, 40 of whom were malnourished (16%). STAMP classified 48.4% of the patients as being under nutritional risk. This tool showed 75% sensitivity and 60.8% specificity when identifying patients under risk according to nutritional assessment. It showed 90% sensitivity and 59.5% specificity when identifying malnourished patients., Comments: Malnutrition was less frequent than that reported in other European countries, although diagnosis technique was different. STAMP is a simple and useful tool for nutritional screening, avoiding the need to assess all patients on admission in order to identify those under nutritional risk.

Histamine in the adult central nervous system (CNS) acts as a neurotransmitter. This amine is one of the first neurotransmitters to appear during development reaching its maximum concentration simultaneously with neuron differentiation peak. This suggests that HA plays an important role in neurogenesis. We have previously shown that HA is able to increase neuronal differentiation of neural stem cells (NSCs) in vitro, by activating the histamine type 1 receptor. However the mechanism(s) by which HA has a neurogenic effect on NSCs has not been explored. Here we explore how HA is able to increase neuron phenotype. Cortex neuroepithelium progenitors were cultured and at passage two treatments with 100 μM HA were given during cell proliferation and differentiation or only during differentiation. Immunocytochemistry was performed on differentiated cultures to detect mature neurons. To explore the expression of certain important transcriptional factors involved on asymmetric cell division and commitment, RT-PCR and qRT-PCR were performed. Results indicate that HA is required during cell proliferation in order to increase neuron differentiation and suggest that this amine increases neuron commitment during the proliferative phase probably by rising prospero1 and neurogenin1 expression., (Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.)

Introduction: One in every four women smoke at the beginning of the pregnancy in Spain; of these, 25-50% give up smoking during gestation and most of them smoke again after childbirth. Maternal smoking has harmful effects on babies, such as low birth-weight with its resulting morbidity. The objective of this study is to compare the anthropometric and socio-cultural characteristics between newborns from smoking motheŕs and those from non- smoking ones., Materials and Methods: Smoking habits and the socio-cultural characteristics were assessed from a sample of 1499 pregnant women, as well as their newborn anthropometric variables of their newborn babies during 2009 in the Aragon region of Spain., Results: In the sample of 1499 pregnant women the prevalence of smoking during pregnancy was 19.6%; among the Spanish women, 23% of them smoked during the gestation compared with only 11% in women from other countries. The smoker mothers were younger and they had a lower educational level than the non smoker ones; however, there were no statistical differences between their anthropometric characteristics. Newborns from smoker women in Aragon had a lower weigh at delivery (3155 vs. 3295 grams: p<.001) and a relative risk of low weight at birth for their gestational age of 2.1 (95% CI: 1.35 - 2.97). The length and the rest of newborn anthropometric variables were also affected., Conclusion: The prevalence of smoking during gestation is high in Aragon. The mothers who smoke are younger and have different socio-cultural characteristics compared with non-smoker mothers. Maternal smoking habits have a harmful effect on newborn nutritional status, representing an avoidable risk of low weight at birth., (Copyright © 2011 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.)

Background: Activin A is a protein that participates principally in reproductive functions. In the adult brain, Activin is neuroprotective, but its role in brain development is still elusive., Methodology/principal Findings: We studied if Activin A influences proliferation, differentiation or survival in rat cerebrocortical neural progenitor cells (NPC). After stimulation of NPC with Activin A, phosphorylation and nuclear translocation of Smad 2/3 were induced. In proliferating NPC, Activin produced a significant decrease in cell area and also a discrete increase in the number of neurons in the presence of the mitogen Fibroblast Growth Factor 2. The percentages of cells incorporating BrdU, or positive for the undifferentiated NPC markers Nestin and Sox2, were unchanged after incubation with Activin. In differentiating conditions, continuous treatment with Activin A significantly increased the number of neurons without affecting astroglial differentiation or causing apoptotic death. In cells cultured by extended periods, Activin treatment produced further increases in the proportion of neurons, excluding premature cell cycle exit. In clonal assays, Activin significantly increased neuronal numbers per colony, supporting an instructive role. Activin-induced neurogenesis was dependent on activation of its receptors, since incubation with the type I receptor inhibitor SB431542 or the ligand-trap Follistatin prevented neuronal differentiation. Interestingly, SB431542 or Follistatin by themselves abolished neurogenesis and increased astrogliogenesis, to a similar extent to that induced by Bone Morphogenetic Protein (BMP)4. Co-incubation of these Activin inhibitors with the BMP antagonist Dorsomorphin restored neuronal and astrocytic differentiation to control levels., Conclusions: Our results show an instructive neuronal effect of Activin A in cortical NPC in vitro, pointing out to a relevant role of this cytokine in the specification of NPC towards a neuronal phenotype.

Background: The identification of the attribution of economic value that users of a health system assign to a health service could be useful in planning these services. The method of contingent valuation can provide information about the user's perception of value in monetary terms, and therefore comparable between services of a very different nature. This study attempts to extract the economic value that the subject, user of primary care nursing services in a public health system, attributes to this service by the method of contingent valuation, based on the perspectives of Willingness to Pay (WTP) and Willingness to Accept [Compensation] (WTA)., Methods/design: This is an economic study with a transversal design. The contingent valuation method will be used to estimate the user's willingness to pay (WTP) for the care received from the primary care nurse and the willingness to accept [compensation] (WTA), were this service eliminated. A survey that meets the requisites of the contingent valuation method will be constructed and pilot-tested. Subsequently, 600 interviews will be performed with subjects chosen by systematic randomized sampling from among those who visit nursing at twenty health centers with different socioeconomic characteristics in the Community of Madrid. The characteristics of the subject and of the care received that can explain the variations in WTP, WTA and in the WTP/WTA ratio expressed will be studied. A theoretical validation of contingent valuation will be performed constructing two explanatory multivariate mixed models in which the dependent variable will be WTP, and the WTP/WTA relationship, respectively., Discussion: The identification of the attribution of economic value to a health service that does not have a direct price at the time of use, such as a visit to primary care nursing, and the definition of a profile of "loss aversion" in reference to the service evaluated, can be relevant elements in planning, enabling incorporating patient preferences to health policy decision-making.

Introduction: Maternal nutritional status is an important factor of adequate intrauterine growth and neonatal weight. The aim of this study is to evaluate the relationship between pre-gestational BMI (Body Mass Index) and breastfeeding duration, as well as infant anthropometric measurements during their first six months of life., Materials and Methods: Anthropometric measurements and the type of feeding were evaluated in a representative sample of 1,547 newborns from our population during 2009, according to their maternal BMI, and also in a sub-cohort of 759 infants followed up to 6 months of life., Results: A total of 72.9% of women had a normal weight, 18.7% were overweight and 8.4% obese. Women with a BMI ≥ 25 kg/m(2) had lower weight gain during pregnancy (P < .001), lower socioeconomic and cultural level (P < .001), and their infants had higher weight at delivery (P=.003) and at 6 months of life, with no differences in body length. Newborn weight increased in relation to maternal BMI, but over 35 kg/m(2) it decreased progressively (P < .001). Breastfeeding prevalence in obese women was 58.5% at hospital postpartum discharge, and 8.6% at six months of life; as opposed to 70.8% and 13.9%, respectively in women with normal BMI., Conclusions: In our sample, maternal obesity is associated with a low socioeconomic and cultural level, higher infant weight at delivery and at 6 months of life, and less prevalence of exclusive breastfeeding; all of them nutritional risk factors in the short and long term., (Copyright © 2010 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.)

Introduction and Objective: Population standards of intrauterine growth are necessary to evaluate if the newborn has grown well, if their nutritional conditions are appropriate and to identify groups at risk as those small for gestational age (SGA). Differences in the number of SGA newborns identified, depending on the standard applied, have been analyzed in this study., Material and Methods: Cross-sectional study conducted in 4,486 Caucasian newborns (2,361 boys and 2,125 girls), born between 35 and 41 weeks. Weight and length valuation was performed following the standard methodology. Percentage of children under the 10(th) percentile for weight and length was calculated depending on the standard used (Olsen et al. 2010, Lubchenco et al. 1966, Delgado et al. 1996, Carrascosa et al. 2008), being diagnosed of SGA., Results: Weight and length were significantly higher in boys than in girls at all ages. 10(th) percentile values defined for every gestational age are globally similar among the different standards and our population, with the clear exception of Lubchenco curves whose 10(th) percentile values are even 300 g. lower for the newborns at the highest gestational ages. Lubchenco charts do not fit the pattern of intrauterine growth of our population and identify a smaller number of SGA. The percentage of SGA of our sample ranged between 1.7% and 14% in depending on the standard, sex and gestational age considered., Conclusion: The number of children classified as SGA is different according to each standard used. Lubchenco charts identify a smaller number of SGA than the others. The rest of curves show similar values and seem to be well adapted for our population. The correct identification of SGA will allow a better assessment of short and long-term risks of these newborns.

Introduction: Growth is a complex phenomenon that has in pediatric age special relevancy because it constitutes a fundamental indicator of nutritional status., Objective: To evaluate differences about weight analysis of infants aged 0-18 months depending on the population reference used., Methods: This is a longitudinal weight and length study in a representative sample of 383 infants from Aragon since birth until 18 months of age. A descriptive analysis was realized and "z-scores" were calculated from five growth curves. Finally there was calculated the percentage of children who were staying above or under 2DS for weight depending on the standard used., Results: 50.1% were males and 49.9% women. Weight and length of the children were higher in girls than in boys in all the ages (p<0.01). Major differences between weight z-score averages from standards were at 6 months and later. The percentage of children on a weight<2 DS ranged between 0.5 and one 3.3% at 18 months of age depending on the standard., Conclusion: Global differences exist when weight is evaluated in the same sample of infants up to 18 months of age depending on different population standards, as well as in the number of children who stay out of the limits of the normality with each of them.

Background: Health services utilization has been studied under several conceptual models. This study is aimed to assess the influence of Health Related Quality of Life (HRQL) on the variability of the primary care consultation utilization under the <>, Methods: A cross-sectional study. Interviews were conducted with 451 subjects at six health centers in the Community of Madrid. Environmental and individual characteristics (predisposing, enabling and need factors) and HRQL (EuroQol-5D) were collected. Annual visits were retrieved from the computerized clinical history., Results: Median utilization was 13 visits/year (interquartile range 7-20). HRQL explained 5,2% of utilization variability, living in high-income areas an additional 2.4%, age a 7.4%, incomes a 1.0% and <> (chronic illnesses or a hospital admission in the last year) explained an additional 4.1% of the variability. Each increase of the tercile in the perception of HRQL was associated with a decrease of 13,8% of the number of visits/year. Living in high-income areas, and each increase of 1000 in the incomes decreased the percentage of annual visits 17.5 % and 9.5% respectively. Age is associated with an increase of 8.0% of annual visits per decade. Suffering from chronic illnesses or a hospital admission in the last year increased the average number of visits/year to 51.9 and 26.5%., Conclusions: HRQL is independently associated with the variability of the demand for the family physician after adjusting by << health need>> factors as the <> proposes.

Background: To evaluate cardiac abnormalities in children with different neuromuscular diseases (NMD) PATIENTS AND METHOD: In 40 patients with NMD, cardiac abnormalities were evaluated by cardiac auscultation, chest X-ray, electrocardiography (ECG), ambulatory Holter ECG and Doppler echography., Results: Sinus tachycardia, high R/S complex, deep Q waves, repolarization disorders, electrical conduction abnormalities, auricular and ventricular extrasystoles, Wolff-Parkinson-White syndrome, mitral valve prolapse and dilated cardiomyopathy were found., Conclusions: The association of cardiac abnormalities in children with NMD is frequent. Conventional ECG monitorization, Holter ECG and echocardiography allow their diagnosis and follow-up.