High rate of autonomic neuropathy in Cornelia de Lange Syndrome.

BACKGROUND: Cornelia de Lange Syndrome (CdLS) is a rare congenital disorder characterized by typical facial features, growth failure, limb abnormalities, and gastroesophageal dysfunction that may be caused by mutations in several genes that disrupt gene regulation early in development. Symptoms in individuals with CdLS suggest that the peripheral nervous system (PNS) is involved, yet there is little direct evidence. METHOD: Somatic nervous system was evaluated by conventional motor and sensory nerve conduction studies and autonomic nervous system by heart rate variability, sympathetic skin response and sudomotor testing. CdLS Clinical Score and genetic studies were also obtained. RESULTS: Sympathetic skin response and sudomotor test were pathological in 35% and 34% of the individuals with CdLS, respectively. Nevertheless, normal values in large fiber nerve function studies. CONCLUSIONS: Autonomic nervous system (ANS) dysfunction is found in many individuals with Cornelia de Lange Syndrome, and could be related to premature aging.

Understanding the electronic properties of BaTiO3 and Er3+ doped BaTiO3 films through confocal scanning microscopy and XPS: the role of oxygen vacancies.

Photonic and electronic properties exist inherently in ferroelectric barium titanate (BaTiO3); severe luminescence quenching also exists due to the insufficient confinement of excitons. In this sense, high optical emission can only be achieved by its chemical and structural modification. Thin BaTiO3 and Er:BaTiO3 films were grown by the spin coating method on a glass substrate at room temperature. Self-trapping of excitons in the thin BaTiO3 film and its structural modification due to the doping with Er3+ ions (Er:BaTiO3) are verified using scanning confocal fluorescence microscopy (SCFM), where self-trapping excitons never occured in its pure state. By thermal treatment and doping (BaTiO3 and Er:BaTiO3) we obtained localization of the excitons, which would further induce lattice strain around the surface defects, to accommodate the self-trapped excitons. With such a self-trapped state, the structure of BaTiO3 generates broadband emission of several overlapping bands between 1.95 and 2.65 eV at room temperature, while the structure Er:BaTiO3 showed defined emission bands at 2.24 and 2.35 eV, with very weak contributions of the emission due to the self-trapping state. The influence of the variation of the excitation wavelength using 1PE and 2PE on the emission bands of BaTiO3 and Er:BaTiO3 is also investigated. The results of enhanced emission bands suggest a clear dependence of the emission intensity on the excitation energy, where a ∼3 fold enhancement in emission has been demonstrated under Er3+ (1.55 eV) excitation, which can be attributed to effective energy transfer between the Er3+ ions. As a result, it is concluded that the developed BaTiO3 and Er:BaTiO3 can pave the way for future photonic devices.

Contrasting effects of an Mdm2 functional polymorphism on tumor phenotypes.

MDM2, an E3 ubiquitin ligase, is a potent inhibitor of the p53 tumor suppressor and is elevated in many human cancers that retain wild-type p53. MDM2 SNP309G is a functional polymorphism that results in elevated levels of MDM2 (due to enhanced SP1 binding to the MDM2 promoter) thus decreasing p53 activity. Mdm2SNP309G/G mice are more prone to spontaneous tumor formation than Mdm2SNP309T/T mice, providing direct evidence for the impact of this SNP in tumor development. We asked whether environmental factors impact SNP309G function and show that SNP309G cooperates with ionizing radiation to exacerbate tumor development. Surprisingly, ultraviolet B light or Benzo(a)pyrene exposure of skin shows that SNP309G allele actually protects against squamous cell carcinoma susceptibility. These contrasting differences led us to interrogate the mechanism by which Mdm2 SNP309 regulates tumor susceptibility in a tissue-specific manner. Although basal Mdm2 levels were significantly higher in most tissues in Mdm2SNP309G/G mice compared with Mdm2SNP309T/T mice, they were significantly lower in Mdm2SNP309G/G keratinocytes, the cell-type susceptible to squamous cell carcinoma. The assessment of potential transcriptional regulators in ENCODE ChIP-seq database identified transcriptional repressor E2F6 as a possible negative regulator of MDM2 expression. Our data show that E2F6 suppresses Mdm2 expression in cells harboring the SNP309G allele but not the SNP309T allele. Thus, Mdm2 SNP309G exhibits tissue-specific regulation and differentially impacts cancer risk.

Inflammation in metabolically healthy and metabolically abnormal adolescents: The HELENA study.

BACKGROUND AND AIMS: Inflammation may influence the cardio-metabolic profile which relates with the risk of chronic diseases. This study aimed to assess the inflammatory status by metabolic health (MH)/body mass index (BMI) category and to assess how inflammatory markers can predict the cardio-metabolic profile in European adolescents, considering BMI. METHODS AND RESULTS: A total of 659 adolescents (295 boys) from a cross-sectional European study were included. Adolescents were classified by metabolic health based on age- and sex-specific cut-off points for glucose, blood pressure, triglycerides, high density cholesterol and BMI. C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin (IL-6), complement factors (C3, C4) and cell adhesion molecules were assessed. RESULTS: Metabolically abnormal (MA) adolescents had higher values of C3 (p < 0.001) and C4 (p = 0.032) compared to those metabolically healthy (MHy). C3 concentrations significantly increased with the deterioration of the metabolic health and BMI (p < 0.001). Adolescents with higher values of CRP had higher probability of being in the overweight/obese-MH group than those allocated in other categories. Finally, high C3 and C4 concentrations increased the probability of having an unfavorable metabolic/BMI status. CONCLUSIONS: Metabolic/BMI status and inflammatory biomarkers are associated, being the CRP, C3 and C4 the most related inflammatory markers with this condition. C3 and C4 were associated with the cardio-metabolic health consistently.

Aspectos prácticos de la extracción, conservación y administración de leche materna en el hogar / Practical aspects of expressing, storing and handling breast milk in the home

El amamantamiento proporciona leche materna no deteriorada al lactante en condiciones naturales. Cuando es necesaria la administración de leche materna extraída, hay riesgo de contaminación y deterioro de la leche. La extracción cuidadosa, el mantenimiento de la cadena de frío en la conservación y el transporte y la manipulación adecuada son esenciales para no alterar sus propiedades (AU)

Breast feeding provides the infant with fresh mother’s milk in natural condition. When expressed breast milk has to be used, there is a risk of contamination and deterioration of the milk. Careful expressing, assuring the cold chain during storage and transport and proper handling are essential if its properties are to be maintained (AU)

Distinct downstream targets manifest p53-dependent pathologies in mice.

Mdm2, the principal negative regulator of p53, is critical for survival, a fact clearly demonstrated by the p53-dependent death of germline or conditional mice following deletion of Mdm2. On the other hand, Mdm2 hypomorphic (Mdm2Puro/Δ7-12) or heterozygous (Mdm2+/-) mice that express either 30 or 50% of normal Mdm2 levels, respectively, are viable but present distinct phenotypes because of increased p53 activity. Mdm2 levels are also transcriptionally regulated by p53. We evaluated the significance of this reciprocal relationship in a new hypomorphic mouse model inheriting an aberrant Mdm2 allele with insertion of the neomycin cassette and deletion of 184-bp sequence in intron 3. These mice also carry mutations in the Mdm2 P2-promoter and thus express suboptimal levels of Mdm2 entirely encoded from the P1-promoter. Resulting mice exhibit abnormalities in skin pigmentation and reproductive tissue architecture, and are subfertile. Notably, all these phenotypes are rescued on a p53-null background. Furthermore, these phenotypes depend on distinct p53 downstream activities as genetic ablation of the pro-apoptotic gene Puma reverts the reproductive abnormalities but not skin hyperpigmentation, whereas deletion of cell cycle arrest gene p21 does not rescue either phenotype. Moreover, p53-mediated upregulation of Kitl influences skin pigmentation. Altogether, these data emphasize tissue-specific p53 activities that regulate cell fate.

Recomendaciones del Grupo de Trabajo de Obesidad de la Sociedad Española de Endocrinología Pediátrica sobre hábitos de alimentación para la prevención de la obesidad y los factores de riesgo cardiovascular en la infancia / Recommendations of the Spanish Paediatric Endocrinology Society Working Group on Obesity on eating habits for the prevention of obesity and cardiovascular risk factors in childhood

La obesidad infantil determina un riesgo elevado de enfermedad cardiovascular. Este artículo realiza una actualización sobre el papel que los factores dietéticos tienen sobre el desarrollo y la prevención de la obesidad en este grupo de edad. Según la evidencia científica, las recomendaciones recogidas son: promover el consumo de hidratos de carbono de absorción lenta y disminuir aquellos con índice glucémico alto, evitar el consumo de bebidas azucaradas, limitar el consumo de grasas a un 30% de las calorías totales diarias y el de grasas saturadas a un 7-10%, reducir la ingesta de colesterol, evitar durante el primer año las fórmulas con alto contenido proteico, aumentar la ingesta de fibra, reducir el aporte de sodio y realizar al menos 4 comidas al día evitando el consumo regular de comida rápida y de snacks

Childhood obesity is associated with a high risk of cardiovascular disease and early mortality. This paper summarises the currently available evidence on the implications of dietary factors on the development and prevention of obesity in paediatric patients. Evidence-based recommendations are: promote the consumption of slowly absorbed carbohydrates and reduce those with a high-glycaemic-index, avoid intake of sugar-sweetened beverages. Fat may provide up to 30-35% of the daily energy intake and saturated fat should provide no more than 10% of daily energy intake; reduce cholesterol intake, avoid formula milk with a high protein content during the first year; promote higher fibre content in the diet, reduce sodium intake, and have at least four meals a day, avoiding regular consumption of fast food and snacks

Heterozygous p53(V172F) mutation in cisplatin-resistant human tumor cells promotes MDM4 recruitment and decreases stability and transactivity of p53.

Cisplatin is an important antitumor agent, but its clinical utility is often limited by multifactorial mechanism of resistance. Loss of tumor suppressor p53 function is a major mechanism that is affected by either mutation in the DNA-binding domain or dysregulation by overexpression of p53 inhibitors MDM2 and MDM4, which destabilize p53 by increasing its proteosomal degradation. In the present study, cisplatin-resistant 2780CP/Cl-16 ovarian tumor cells expressed a heterozygous, temperature-sensitive p53(V172F) mutation, which reduced p53 half-life by two- to threefold compared with homozygous wild-type (wt) p53 in parental A2780 cells. Although reduced p53 stability in 2780CP/Cl-16 cells was associated with moderate cellular overexpression of MDM2 or MDM4 (<1.5-fold), their binding to p53 was substantially enhanced (five- to eightfold). The analogous cisplatin-resistant 2780CP/Cl-24 cells, which express loss of p53 heterozygosity, retained the p53(V172F) mutation and high p53-MDM4 binding, but demonstrated lower p53-bound MDM2 that was associated with reduced p53 ubiquitination and enhanced p53 stability. The inference that p53 was unstable as a heteromeric p53(wt)/p53(V172F) complex was confirmed in 2780CP/Cl-24 cells transfected with wt p53 or multimer-inhibiting p53(L344P) mutant, and further supported by normalization of p53 stability in both resistant cell lines grown at the permissive temperature of 32.5 °C. Surprisingly, in 2780CP/Cl-16 and 2780CP/Cl-24 models, cisplatin-induced transactivity of p53 was attenuated at 37 °C, and this correlated with cisplatin resistance. However, downregulation of MDM2 or MDM4 by small interfering RNA in either resistant cell line induced p53 and restored p21 transactivation at 37 °C, as did cisplatin-induced DNA damage at 32.5 °C that coincided with reduced p53-MDM4 binding and cisplatin resistance. These results demonstrate that cisplatin-mediated p53(V172F) mutation regulates p53 stability at the normothermic temperature, but it is the increased recruitment of MDM4 by the homomeric or heteromeric mutant p53(V172F) complex that inhibits p53-dependent transactivation. This represents a novel cellular mechanism of p53 inhibition, and, thereby, induction of cisplatin resistance.

Novel p53 target genes secreted by the liver are involved in non-cell-autonomous regulation.

The tumor-suppressor p53 is a transcription factor that prevents cancer development and is involved in regulation of various physiological processes. This is mediated both by induction of cell cycle arrest and apoptosis and by controlling the expression of a plethora of target genes, including secreted proteins. It has been demonstrated that p53 may exert its effect in non-cell-autonomous manner by modulating the expression of genes that encode for secreted factors. In this study, we utilized our microarray data to identify and characterize novel p53 target genes expressed in human liver cells and associated with steroid hormones processing and transfer. We identified the steroid hormones binding factors, sex hormone-binding globulin (SHBG), corticosteroid-binding globulin (CBG) and cytochrome P450 family 21 subfamily A polypeptide 2, as novel p53 target genes. Their expression and secretion was increased following p53 activation in various hepatic cells. We observed that p53 wild-type mice exhibited higher levels of CBG compared with their p53 null counterparts. We demonstrated that the induction of the steroid hormones binding factors can be mediated by binding to specific p53 responsive elements within their promoters. In addition, utilizing conditioned medium experiments we have shown that p53-dependent induction of SHBG secretion from liver cells enhances apoptosis of breast cancer cells. Moreover, depletion of SHBG abolished the induction of breast cancer cells death. The newly identified p53 target genes suggest a novel non-cell-autonomous tumor-suppressive regulation mediated by p53 that is central for maintaining organism homeostasis.

MDM4/HIPK2/p53 cytoplasmic assembly uncovers coordinated repression of molecules with anti-apoptotic activity during early DNA damage response.

The p53 inhibitor, MDM4 (MDMX) is a cytoplasmic protein with p53-activating function under DNA damage conditions. Particularly, MDM4 promotes phosphorylation of p53 at Ser46, a modification that precedes different p53 activities. We investigated the mechanism by which MDM4 promotes this p53 modification and its consequences in untransformed mammary epithelial cells and tissues. In response to severe DNA damage, MDM4 stimulates p53Ser46(P) by binding and stabilizing serine-threonine kinase HIPK2. Under these conditions, the p53-inhibitory complex, MDM4/MDM2, dissociates and this allows MDM4 to promote p53/HIPK2 functional interaction. Comparative proteomic analysis of DNA damage-treated cells versus -untreated cells evidenced a diffuse downregulation of proteins with anti-apoptotic activity, some of which were targets of p53Ser46(P)/HIPK2 repressive activity. Importantly, MDM4 depletion abolishes the downregulation of these proteins indicating the requirement of MDM4 to promote p53-mediated transcriptional repression. Consistently, MDM4-mediated HIPK2/p53 activation precedes HIPK2/p53 nuclear translocation and activity. Noteworthy, repression of these proteins was evident also in mammary glands of mice subjected to γ-irradiation and was significantly enhanced in transgenic mice overexpressing MDM4. This study evidences the flexibility of MDM2/MDM4 heterodimer, which allows the development of a positive activity of cytoplasmic MDM4 towards p53-mediated transcriptional function. Noteworthy, this activity uncovers coordinated repression of molecules with shared anti-apoptotic function which precedes active cell apoptosis and that are frequently overexpressed and/or markers of tumour phenotype in human cancer.

[Recommendations of the Spanish Paediatric Endocrinology Society Working Group on Obesity on eating habits for the prevention of obesity and cardiovascular risk factors in childhood]. / Recomendaciones del Grupo de Trabajo de Obesidad de la Sociedad Española de Endocrinología Pediátrica sobre hábitos de alimentación para la prevención de la obesidad y los factores de riesgo cardiovascular en la infancia.

Childhood obesity is associated with a high risk of cardiovascular disease and early mortality. This paper summarises the currently available evidence on the implications of dietary factors on the development and prevention of obesity in paediatric patients. Evidence-based recommendations are: promote the consumption of slowly absorbed carbohydrates and reduce those with a high-glycaemic-index, avoid intake of sugar-sweetened beverages. Fat may provide up to 30-35% of the daily energy intake and saturated fat should provide no more than 10% of daily energy intake; reduce cholesterol intake, avoid formula milk with a high protein content during the first year; promote higher fibre content in the diet, reduce sodium intake, and have at least four meals a day, avoiding regular consumption of fast food and snacks.

Mdm2 overexpression and p73 loss exacerbate genomic instability and dampen apoptosis, resulting in B-cell lymphoma.

Many human tumors express high levels of the p53 inhibitor Mdm2, resulting from amplification of the Mdm2 locus or aberrant post-translational regulation of the Mdm2 protein. While the importance of Mdm2 in regulating p53 is clear, Mdm2 also has p53-independent roles. For example, overexpression of Mdm2 results in genomic instability in a p53-independent manner. In addition, Mdm2 has many additional binding partners, some of which, such as the tumor suppressor p73, have also been implicated in genomic instability. In this study, cells and tumors with Mdm2 overexpression and p73 loss exhibit increased genomic instability as compared with either alteration alone and cooperate in development of B-cell lymphomagenesis. Cytogenetic analysis of mouse embryonic fibroblasts and pre-malignant B cells demonstrates that loss of p73 exacerbates the chromosome breaks and fusions observed in Mdm2(Tg) cells. B-cell lymphomas from Mdm2(Tg);p73(+/-) mice retain the remaining p73 allele, exhibit elevated levels of the antiapoptotic protein Bcl2 and thus dampen apoptosis. In summary, Mdm2 overexpression and p73 loss cooperate in genomic instability and tumor development, indicating that the oncogenic function of Mdm2 is a combined effect of inhibiting p53 and p73 functions. Given that p73 is lost or silenced in human B-cell lymphomas, the Mdm2(Tg);p73(+/-) mouse serves as a model for human disease and may provide additional insight into the pathways that contribute to B-cell lymphomagenesis.

Recomendaciones para la asistencia respiratoria en el recién nacido (III). Surfactante y óxido nítrico / Recommendations for respiratory support in the newborn (III). Surfactant and nitric oxide

Las recomendaciones incluidas en este documento forman parte de una revisión actualizada de la asistencia respiratoria en el recién nacido. Están estructuradas en 12 módulos y en este trabajo se presenta el módulo 7. El contenido de cada módulo es el resultado del consenso de los miembros del Grupo Respiratorio y Surfactante de la Sociedad Española de Neonatología. Representan una síntesis de los trabajos publicados y de la experiencia clínica de cada uno de los miembros del grupo (AU)

The recommendations included in this document will be part a series of updated reviews of the literature on respiratory support in the newborn infant. These recommendations are structured into twelve modules, and in this work module 7 is presented. Each module is the result of a consensus process including all members of the Surfactant and Respiratory Group of the Spanish Society of Neonatology. They represent a summary of the published papers on each specific topic, and of the clinical experience of each one of the members of the group (AU)

Improving survival by exploiting tumour dependence on stabilized mutant p53 for treatment.

Missense mutations in p53 generate aberrant proteins with abrogated tumour suppressor functions that can also acquire oncogenic gain-of-function activities that promote malignant progression, invasion, metastasis and chemoresistance. Mutant p53 (mutp53) proteins undergo massive constitutive stabilization specifically in tumours, which is the key requisite for the acquisition of gain-of-functions activities. Although currently 11 million patients worldwide live with tumours expressing highly stabilized mutp53, it is unknown whether mutp53 is a therapeutic target in vivo. Here we use a novel mutp53 mouse model expressing an inactivatable R248Q hotspot mutation (floxQ) to show that tumours depend on sustained mutp53 expression. Upon tamoxifen-induced mutp53 ablation, allotransplanted and autochthonous tumours curb their growth, thus extending animal survival by 37%, and advanced tumours undergo apoptosis and tumour regression or stagnation. The HSP90/HDAC6 chaperone machinery, which is significantly upregulated in cancer compared with normal tissues, is a major determinant of mutp53 stabilization. We show that long-term HSP90 inhibition significantly extends the survival of mutp53 Q/- (R248Q allele) and H/H (R172H allele) mice by 59% and 48%, respectively, but not their corresponding p53(-/-) littermates. This mutp53-dependent drug effect occurs in H/H mice treated with 17DMAG+SAHA and in H/H and Q/- mice treated with the potent Hsp90 inhibitor ganetespib. Notably, drug activity correlates with induction of mutp53 degradation, tumour apoptosis and prevention of T-cell lymphomagenesis. These proof-of-principle data identify mutp53 as an actionable cancer-specific drug target.

[Recommendations for respiratory support in the newborn (iii). Surfactant and nitric oxide]. / Recomendaciones para la asistencia respiratoria en el recién nacido (iii). Surfactante y óxido nítrico.

The recommendations included in this document will be part a series of updated reviews of the literature on respiratory support in the newborn infant. These recommendations are structured into twelve modules, and in this work module 7 is presented. Each module is the result of a consensus process including all members of the Surfactant and Respiratory Group of the Spanish Society of Neonatology. They represent a summary of the published papers on each specific topic, and of the clinical experience of each one of the members of the group.

Necrosis grasa subcutánea complicada tras tratamiento con hipotermia terapéutica por encefalopatía hipóxico-isquémica grave / Complicated subcutaneous fat necrosis after hypothermia treatment for severe hypoxic-ischemic encephalopathy

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Impacto en la práctica clínica de la apertura de un banco de leche en una unidad neonatal / Clinical impact of opening a human milk bank in a neonatal unit

INTRODUCCIÓN: Los beneficios de la leche donada frente a la fórmula artificial están demostrados, sin embargo no se conoce la influencia de la apertura de un banco de leche en la práctica clínica habitual. El objetivo de este estudio fue medir el impacto en la práctica clínica de la disponibilidad de leche donada para la nutrición de los prematuros ≤32 semanas de edad gestacional. MÉTODOS: Estudio antes-después de la apertura de un banco de leche. Se incluyeron los ≤32 semanas nacidos en el Hospital 12 de Octubre de julio-diciembre de 2005 y de enero-junio de 2008 (6 primeros meses tras la apertura del banco de leche). RESULTADOS: La apertura del banco de leche permitió empezar 31h antes (p < 0,001) la alimentación enteral, se alcanzaron 59,5h antes los 100ml/kg/día (p < 0,001) y 52h antes los 150ml/kg/día (p = 0,002), permitiendo retirar 72h antes la nutrición parenteral. En ningún prematuro se inició la alimentación enteral con fórmula artificial, la exposición a la misma en los primeros 15días de vida bajó del 50 al 16,6% y su consumo durante los primeros 28 días fue significativamente menor. La cantidad consumida de leche de la propia madre fue mayor, al igual que la tasa de lactancia materna exclusiva al alta (54 vs. 40%). CONCLUSIONES: Disponer de leche donada ha permitido avanzar más rápidamente con la nutrición enteral y retirar antes la nutrición parenteral. La exposición a fórmula artificial ha sido menor y mayor el consumo de leche de madre propia y la lactancia materna al alta

INTRODUCTION: The benefits of donor human milk compared with artificial formulas have been well demonstrated; nevertheless the impact in the clinical practice of opening a human milk bank within a neonatal unit has not yet been studied. The main aim of this study was to analyze the impact on the clinical practice of opening a human milk bank in a neonatal unit to provide donor human milk for preterm infants ≤32 weeks of gestational age. METHODS: A before and after study was designed, with the intervention being the opening a human milk bank. Preterm infants ≤32 weeks of gestational age born in the Hospital 12 Octubre from July to December 2005 and January to June 2008 (firsts 6 months after opening the human milk bank) were included. RESULTS: After opening the human milk bank, enteral feedings were started 31h before (P<0.001), 100ml/kg/day were achieved 59.5h before (P<0.001) and 150ml/kg/day 52h before (P=0.002). Enteral feedings were never started LM with artificial formula, the exposure to formula in the first 15 days of life was reduced from 50% to 16.6%, and it's consumption during the first 28 days of life was significantly reduced. There was a higher consumption of own mother's milk during the hospital stay, and a higher rate of exclusive breastfeeding at hospital discharge (54% vs 40%). CONCLUSIONS: The availability of donor human milk has led to quicker progression with enteral feedings and earlier withdrawal of parenteral nutrition. It has reduced the exposure to artificial formulas, and has also increased the intake of own mother's milk during the hospital stay and the rate of exclusive breastfeeding at hospital discharge

Epidemiología de la diabetes mellitus tipo 1 en menores de 15 años en España / Epidemiology of type 1 diabetes mellitus in children in Spain

INTRODUCCIÓN: Los estudios epidemiológicos sobre diabetes mellitus tipo 1 (DM1) realizados en múltiples países y regiones han contribuido al conocimiento de la epidemiología de la enfermedad en menores de 15 años. En España se han realizado estudios en casi todas las comunidades autónomas, si bien las cifras de incidencia a nivel nacional no son todavía bien conocidas. MATERIAL Y MÉTODOS: Revisión bibliográfica de las publicaciones y comunicaciones sobre epidemiología de la DM1 en menores de 15 años en España. Se han seleccionado las referencias que aportasen datos de pacientes menores de 15 años. RESULTADOS: Se han encontrado estudios en casi todas las comunidades autónomas. La metodología de los estudios realizados es heterogénea, encontrando diferencias en cuanto al ámbito de realización, duración, periodo estudiado, límite superior de edad y método de recogida de datos. Las tasas de incidencia comunicadas varían desde los 11,5 casos/100.000 habitantes-año en Asturias hasta los 27,6 de Castilla-La Mancha. En ocasiones se especifica el porcentaje de casos que presentan cetoacidosis diabética en el momento del diagnóstico, habitualmente en el rango del 25-40%. CONCLUSIONES: En España se han realizado múltiples estudios epidemiológicos de DM1 en menores de 15 años, con una metodología heterogénea. La incidencia media de DM1 en menores de 15 años en España estimada en base a los estudios revisados sería de 17,69 casos/100.000 habitantes-año. Creemos conveniente mantener los registros de DM1 en funcionamiento y crearlos en aquellas comunidades autónomas donde no existen, así como unificar en lo posible la metodología utilizada de cara a obtener datos precisos sobre la epidemiología de la DM1 en España y conocer la evolución de la incidencia de la enfermedad en los próximos años

INTRODUCTION: Epidemiological studies in many regions and countries have contributed to determining the epidemiology of type 1 diabetes (T1DM) in children less than 15 years old. Studies in many regions of Spain have been published, but the national incidence is not really known. MATERIAL AND METHODS: A review was made of the publications on the epidemiology of T1DM in Spain, selecting the references on patients less than 15 years old. RESULTS: Many epidemiological studies on T1DM in almost all regions in Spain have been published. The methodology of these studies is heterogeneous, with variations in geographical definition, duration, period of study, limit of age, and data collection. The incidence rates are variable, from 11.5 cases per 100,000/year in Asturias to 27.6 in Castilla-La Mancha. Some studies report the percentage of diabetic ketoacidosis at the time of diagnosis, which is usually in the range of 25-40%. CONCLUSIONS: Although there have been various epidemiological studies on T1DM in almost all regions in Spain, the methodology is heterogeneous. The mean incidence of T1DM in children less than 15 years old in Spain, stimated from the selected studies is 17,69 cases per 100,000/year. T1DM registers need to be created and updated, using standardized methodology, to get more reliable data of the epidemiology of T1DM in Spain in the near future

Tailor-made directional emission in nanoimprinted plasmonic-based light-emitting devices.

We demonstrate an enhanced and tailor-made directional emission of light-emitting devices using nanoimprinted hexagonal arrays of aluminum nanoparticles. Fourier microscopy reveals that the luminescence of the device is not only determined by the material properties of the organic dye molecules but is also strongly influenced by the coherent scattering resulting from periodically arranged metal nanoparticles. Emitters can couple to lattice-induced hybrid plasmonic-photonic modes sustained by plasmonic arrays. Such modes enhance the spatial coherence of an emitting layer, allowing the efficient beaming of the emission along narrow angular and spectral ranges. We show that tailoring the separation of the nanoparticles in the array yields an accurate angular distribution of the emission. This combination of large-area metal nanostructures fabricated by nanoimprint lithography and light-emitting devices is beneficial for the design and optimization of solid-state lighting systems.