[Construction of a deprivation index by Basic Healthcare Area in Aragon using Population and Housing Census 2011]. / Construcción de un índice de privación por zona básica de salud en Aragón a partir de datos de censo de 2011.

OBJECTIVE: The measurement of inequalities using composite indicators facilitates the prioritization and implementation of public health actions. The most commonly source of information used for this has been the Population and Housing Census of 2011 (PCH_2011).The objective of this study was to evaluate the use of PHC_2011 and develop a deprivation index (DI) by Basic Healthcare Area (BHA) and to analyse its association with mortality in Aragon. METHODS: Ecological study by BHA. Since PHC_2011 was a sample of the population it was validated by the Chi-square test for homogeneity. 26 socioeconomic indicators were calculated. Spearman correlation coefficients were used to evaluate the relationship between socioeconomic indicators and Standardized Mortality Ratios (SMR). Principal Component Analyses (PCA) were conducted using the indicators in which a significant correlation was found. Components with eigenvalues higher than 1 were extracted, and the rotated matrix (Varimax) was obtained. PCA from each component were conducted, extracting only one factor. BHA were grouped into, according to the deprivation index values. Mortality rates adjusted to the European Standard Population by age, sex and quartile were calculated. The most discriminant factor by quartiles was considered DI. A different DI for urban areas was obtained from the same variables. RESULTS: The validation of PHC sample detected 4 underrepresented BHA. 17 socioeconomic indicators were significatively correlated with SMR. From the first PCA, 3 components were obtained. The DI included %unemployment, %eventual workers, % insufficient education 16-64 years old and %foreigners. The % of variance explained by the DI was 59.7% and 73.8% in urban areas. In men, mortality in the quartile with the lowest deprivation (544,7 per 105; CI95%: 515,8-573,6) was significatively lower than in the most deprivated areas(618,7 per 105;CI95%:589,4-648,0). CONCLUSIONS: This new DI allows us to identify deprived BHA. This is a useful tool to bring to light health inequalities and to plan interventions according to population´s needs.

OBJETIVO: La medición de las desigualdades mediante indicadores compuestos facilita la priorización y puesta en marcha de acciones de salud pública. La fuente de información más comúnmente utilizada para ello ha sido el Censo de Población y viviendas de 2011 (CPV_2011). El objetivo fue validar la utilización del CPV_2011 por Zona de Salud (ZBS) y construir un índice de privación (IP) por ZBS así como analizar su asociación con la mortalidad en Aragón. METODOS: Estudio ecológico por ZBS. El CPV_2011, con diseño muestral, se validó mediante un test de homogeneidad de Chi_cuadrado y se calcularon 26 indicadores socioeconómicos. Se obtuvo el coeficiente de correlación de Spearman entre indicadores socioeconómicos y Razones de Mortalidad Estandarizadas (REM). Se realizó un análisis de componentes principales (ACP) con los indicadores correlacionados significativamente, extrayendo los componentes con autovalores mayores a 1 y se obtuvo la matriz rotada (Varimax). Se realizaron ACP con las variables de cada componente extrayendo un único factor. Se agruparon las ZBS en cuartiles, según el factor calculando tasas de mortalidad ajustadas a población estándar europea por edad, sexo y cuartil. El factor que más discrimina por cuartiles se consideró IP y se recalculó para ZBS urbanas con idénticas variables. RESULTADOS: La validación de la muestra del CPV_2011, detectó cuatro ZBS infrarrepresentadas. 17 indicadores socioeconómicos se correlacionaron con REM. Del primer ACP se extrajeron 3 componentes, eligiendo como IP, el formado por %Desempleo, %Asalariados eventuales, %Instrucción Insuficiente 16-64 años y %Extranjeros. Las varianzas explicadas fueron 59,7% y 73,8% en el IP urbano. En hombres, la mortalidad en el cuartil menos privado (544,7 por 105; IC95%:515,8-573,6), fue inferior a la del más privado (618,7 por 105; IC95%:589,4,648,0). CONCLUSIONES: El IP permite identificar ZBS desfavorecidas constituyendo una herramienta para evidenciar desigualdades y planificar intervenciones según necesidades.

GraftFast Surface Engineering to Improve MOF Nanoparticles Furtiveness.

Controlling the outer surface of nanometric metal-organic frameworks (nanoMOFs) and further understanding the in vivo effect of the coated material are crucial for the convenient biomedical applications of MOFs. However, in most studies, the surface modification protocol is often associated with significant toxicity and/or lack of selectivity. As an alternative, how the highly selective and general grafting GraftFast method leads, through a green and simple process, to the successful attachment of multifunctional biopolymers (polyethylene glycol (PEG) and hyaluronic acid) on the external surface of nanoMOFs is reported. In particular, effectively PEGylated iron trimesate MIL-100(Fe) nanoparticles (NPs) exhibit suitable grafting stability and superior chemical and colloidal stability in different biofluids, while conserving full porosity and allowing the adsorption of bioactive molecules (cosmetic and antitumor agents). Furthermore, the nature of the MOF-PEG interaction is deeply investigated using high-resolution soft X-ray spectroscopy. Finally, a cell penetration study using the radio-labeled antitumor agent gemcitabine monophosphate (3 H-GMP)-loaded MIL-100(Fe)@PEG NPs shows reduced macrophage phagocytosis, confirming a significant in vitro PEG furtiveness.

Quantification of the cellular dose and characterization of nanoparticle transport during in vitro testing.

BACKGROUND: The constant increase of the use of nanomaterials in consumer products is making increasingly urgent that standardized and reliable in vitro test methods for toxicity screening be made available to the scientific community. For this purpose, the determination of the cellular dose, i.e. the amount of nanomaterials effectively in contact with the cells is fundamental for a trustworthy determination of nanomaterial dose responses. This has often been overlooked in the literature making it difficult to undertake a comparison of datasets from different studies. Characterization of the mechanisms involved in nanomaterial transport and the determination of the cellular dose is essential for the development of predictive numerical models and reliable in vitro screening methods. RESULTS: This work aims to relate key physico-chemical properties of gold nanoparticles (NPs) to the kinetics of their deposition on the cellular monolayer. Firstly, an extensive characterization of NPs in complete culture cell medium was performed to determine the diameter and the apparent mass density of the formed NP-serum protein complexes. Subsequently, the kinetics of deposition were studied by UV-vis absorbance measurements in the presence or absence of cells. The fraction of NPs deposited on the cellular layer was found to be highly dependent on NP size and apparent density because these two parameters influence the NP transport. The NP deposition occurred in two phases: phase 1, which consists of cellular uptake driven by the NP-cell affinity, and phase 2 consisting mainly of NP deposition onto the cellular membrane. CONCLUSION: The fraction of deposited NPs is very different from the initial concentration applied in the in vitro assay, and is highly dependent of the size and density of the NPs, on the associated transport rate and on the exposure duration. This study shows that an accurate characterization is needed and suitable experimental conditions such as initial concentration of NPs and liquid height in the wells has to be considered since they strongly influence the cellular dose and the nature of interactions of NPs with the cells.

Synthesis of Nanoscale Coordination Polymers in Femtoliter Reactors on Surfaces.

In the present work, AFM-assisted lithography was used to perform the synthesis of a coordination polymer inside femtoliter droplets deposited on surfaces. For this, solutions of the metal salt and the organic ligand were independently transferred to adjacent tips of the same AFM probe array and were sequentially delivered on the same position of the surface, creating femtoliter-sized reaction vessels where the coordination reaction and particle growth occurred. Alternatively, the two reagents were mixed in the cantilever array by loading an excess of the inks, and transferred to the surface immediately after, before the precipitation of the coordination polymer took place. The in situ synthesis allowed the reproducible obtaining of round-shaped coordination polymer nanostructures with control over their XY positioning on the surface, as characterized by microscopy and spectroscopy techniques.

[Splenic lymphangioma. A rare tumour. Presentation of 3 cases and a literature review]. / Linfangioma esplénico. Un tumor raro. Presentación de 3 casos y revisión de la bibliografía.

BACKGROUND: Lymphangiomas are benign tumours, considered to be congenital malformations of the lymphatic system that predominately affect children, with only a few cases reported in adults. The most common sites of these lesions are the neck (75%) and axillary region (20%), but rarely found in the spleen. OBJECTIVE: A description is presented of 3 cases of incidentally detected splenic lymphangioma, one in a child and in 2 adults, respectively, as well as a literature review. CLINICAL CASES: After a clinical and physical examination, all patients had an abdominal ultrasound, CT scan and a complete splenectomy, followed by a histopathological study on the removed spleen. Two patients were asymptomatic, and the paediatric patient referred to intermittent abdominal pain without other symptoms. The clinical and physical examinations related to the mass were negative. The final diagnosis was based on a combination of radiological and histopathological findings. Total splenectomy was undertaken in all cases without complications. CONCLUSIONS: Splenic lymphangioma is very rare, and more so in adults. This condition is often asymptomatic and is incidentally detected by imagenology due to any other differet cause. The final diagnosis should be based on a combination of clinical, radiological, and histopathological findings. Splenectomy is the treatment of choice and the prognosis is good.

Heparin-engineered mesoporous iron metal-organic framework nanoparticles: toward stealth drug nanocarriers.

The specific modification of the outer surface of the promising porous metal-organic framework nanocarriers (nanoMOFs) preserving their characteristic porosity is still a major challenge. Here a simple, fast, and biofriendly method for the external functionalization of the benchmarked mesoporous iron(III) trimesate nanoparticles MIL-100(Fe) with heparin, a biopolymer associated with longer-blood circulation times is reported. First, the coated nanoparticles showed intact crystalline structure and porosity with improved colloidal stability under simulated physiological conditions, preserving in addition its encapsulation and controlled release capacities. The effect of the heparin coating on the nanoMOF interactions with the biological environment is evaluated through cell uptake, cytotoxicity, oxidative stress, cytokine production, complement activation, and protein adsorption analysis. These results confirmed that the heparin coating endowed the nanoMOFs with improved biological properties, such as reduced cell recognition, lack of complement activation, and reactive oxygen species production. Overall, the ability to coat the surface of the nanoMOFs using a simple and straight-forward approach could be taken as a way to enhance the versatility and, thus, the potential of porous MOF nanoparticles in biomedicine.

7Be-recoil radiolabelling of industrially manufactured silica nanoparticles.

Radiolabelling of industrially manufactured nanoparticles is useful for nanoparticle dosimetry in biodistribution or cellular uptake studies for hazard and risk assessment. Ideally for such purposes, any chemical processing post production should be avoided as it may change the physico-chemical characteristics of the industrially manufactured species. In many cases, proton irradiation of nanoparticles allows radiolabelling by transmutation of a tiny fraction of their constituent atoms into radionuclides. However, not all types of nanoparticles offer nuclear reactions leading to radionuclides with adequate radiotracer properties. We describe here a process whereby in such cases nanoparticles can be labelled with 7Be, which exhibits a physical half-life of 53.29 days and emits γ-rays of 478 keV energy, and is suitable for most radiotracer studies. 7Be is produced via the proton-induced nuclear reaction 7Li(p,n)7Be in a fine-grained lithium compound with which the nanoparticles are mixed. The high recoil energy of 7Be atoms gives them a range that allows the 7Be-recoils to be transferred from the lithium compound into the nanoparticles by recoil implantation. The nanoparticles can be recovered from the mixture by dissolving the lithium compound and subsequent filtration or centrifugation. The method has been applied to radiolabel industrially manufactured SiO2 nanoparticles. The process can be controlled in such a way that no alterations of the 7Be-labelled nanoparticles are detectable by dynamic light scattering, X-ray diffraction and electron microscopy. Moreover, cyclotrons with maximum proton energies of 17-18 MeV that are available in most medical research centres could be used for this purpose.

Bioinspired catechol-terminated self-assembled monolayers with enhanced adhesion properties.

The role of the catechol moiety in the adhesive properties of mussel proteins and related synthetic materials has been extensively studied in the last years but still remains elusive. Here, a simplified model approach is presented based on a self-assembled monolayer (SAM) of upward-facing catechols thiol-bound to epitaxial gold substrates. The orientation of the catechol moieties is confirmed by spectroscopy, which also showed lack of significant amounts of interfering o-quinones. Local force-distance curves on the SAM measured by atomic force microscopy (AFM) shows an average adhesion force of 45 nN, stronger than that of a reference polydopamine coating, along with higher reproducibility and less statistical dispersion. This is attributed to the superior chemical and topographical homogeneity of the SAM coating. Catechol-terminated SAMs are also obtained on high-roughness gold substrates that show the ability to assemble magnetic nanoparticles, despite their lack of enhanced adhesion at the molecular level. Finally, the influence of the catechol group on the formation and quality of the SAM is explored both theoretically (molecular dynamics simulations) and experimentally using direct-write AFM lithography.

Understanding the colloidal stability of the mesoporous MIL-100(Fe) nanoparticles in physiological media.

The colloidal and chemical stability of nanoparticles of the nontoxic and biodegradable iron(III) trimesate MIL-100(Fe) nanocarrier have been evaluated in the presence of a series of simulated physiological fluids for intravenous and oral administration. MIL-100(Fe) nanoparticles exhibit an appropriate colloidal stability and biodegradability, mainly dependent on both the nature of their physicochemical surface and the media composition, being a priori compatible with their biomedical use.

Mn12 single molecule magnets deposited on µ-SQUID sensors: the role of interphases and structural modifications.

Direct measurements of the linear ac susceptibility and magnetic relaxation of a few Mn12 monolayers deposited on a µ-SQUID sensor are reported. In order to integrate the molecules into the device, DPN has been the technique of choice. It enabled the structuration of the molecules on the most sensitive areas of the sensor without the need for any previous functionalization of the molecule or the substrate, while controlling the number of molecular units deposited on each array. The measurements reveal that their characteristic SMM behaviour is lost, a fact that is attributed to molecular distortions originated by the strong surface tensions arising at the molecular interphases.

Controlled positioning of nanoparticles on graphene by noninvasive AFM lithography.

Atomic force microscopy is shown to be an excellent lithographic technique to directly deposit nanoparticles on graphene by capillary transport without any previous functionalization of neither the nanoparticles nor the graphene surface while preserving its integrity and conductivity properties. Moreover this technique allows for (sub)micrometric control on the positioning thanks to a new three-step protocol that has been designed with this aim. With this methodology the exact target coordinates are registered by scanning the tip over the predetermined area previous to its coating with the ink and deposition. As a proof-of-concept, this strategy has successfully allowed the controlled deposition of few nanoparticles on 1 µm(2) preselected sites of a graphene surface with high accuracy.

Structuration and integration of magnetic nanoparticles on surfaces and devices.

Different experimental approaches used for structuration of magnetic nanoparticles on surfaces are reviewed. Nanoparticles tend to organize on surfaces through self-assembly mechanisms controlled by non-covalent interactions which are modulated by their shape, size and morphology as well as by other external parameters such as the nature of the solvent or the capping layer. Further control on the structuration can be achieved by the use of external magnetic fields or other structuring techniques, mainly lithographic or atomic force microscopy (AFM)-based techniques. Moreover, results can be improved by chemical functionalization or the use of biological templates. Chemical functionalization of the nanoparticles and/or the surface ensures a proper stability as well as control of the formation of a (sub)monolayer. On the other hand, the use of biological templates facilitates the structuration of several families of nanoparticles, which otherwise may be difficult to form, simply by establishing the experimental conditions required for the structuration of the organic capsule. All these experimental efforts are directed ultimately to the integration of magnetic nanoparticles in sensors which constitute the future generation of hybrid magnetic devices.

Primary diffuse leptomeningeal gliomatosis mimicking meningeal tuberculosis.

Primary diffuse leptomeningeal gliomatosis (PDLG) is a rare condition, with only 45 cases recorded to date, characterized by infiltration of the meninges by glial cells without evidence of primary tumor in the brain or spinal cord parenchyma. Here, we describe a patient with PDLG who was managed with tuberculostatic drugs owing to multiple findings that were suggestive of tuberculous meningitis. A 19-year-old woman presented with headaches and behavioral changes. A sudden decrease in visual acuity with papilledema, bilateral sixth nerve palsies, and neck stiffness developed. Lumbar puncture showed elevated opening pressure (50 cm H2O). Cerebrospinal fluid (CSF) analysis showed glucose 30 mg/dL, protein 26.5 mg/dL, white blood cell count 150 (60% lymphocytes, 40% neutrophils). The second sample of CSF provided adenosine deaminase activity 21.9 U/L. Polymerase chain reaction for Koch's bacillus was positive in the third CSF sample. Magnetic resonance imaging revealed meningeal thickening of the quadrigeminal cistern, tentorium cerebelli, cerebral convexity, and spinal cord, with gadolinium enhancement in nodular lesions. The patient died 22 weeks after symptom onset owing to brainstem infarction. Postmortem pathologic studies revealed PDLG. This entity should be included in the differential diagnosis of tuberculous meningitis that does not respond to treatment with antituberculous drugs. Surgical biopsy should be considered in contrast-enhanced areas in magnetic resonance imaging.

[Signet ring cell carcinoma of the ampulla of Vater]. / Carcinoma de células en anillo de sello de la ampolla de Vater.

INTRODUCTION: Signet ring cell carcinoma of the ampulla of Vater is a rare entity and less than 20 cases have been described in the literature. We report the cases of two patients with this disease and provide a literature review of previous studies. CASE REPORT: We describe two patients with obstructive jaundice. Abdominal ultrasonography and abdominal computed tomography showed dilatation of the intrahepatic and common bile duct. Duodenoscopy indicated a protruding mass on the ampulla of Vater. Histopathological examination showed round cells and their nuclei were located on one side with prominent signet-ring features. One patient underwent a cephalic pancreatoduodenectomy with lymphadenectomy and the other a total pancreatectomy. DISCUSSION: Signet ring cell carcinoma of the ampulla of Vater has only been described in isolated cases in the literature. Therefore, the clinicopathological features and prognosis of this disease have not yet been well defined.

Aurora B kinase expression in laryngeal squamous cell carcinoma and its prognostic implications.

AIMS: To investigate the clinical and prognostic significance of Aurora B in laryngeal squamous cell carcinomas (LSCC). METHODS AND RESULTS: Aurora B protein expression was analysed in 259 LSCC. The proliferation index (Ki67) and the expression of other cell cycle control proteins, such as Aurora A, survivin and p53 was also determined. Aurora B was highly expressed in 55.4% of LSCC. High Aurora B expression levels were correlated with tumour recurrence (P=0.01), death from disease (P=0.05) and decreased disease-free survival (P=0.013) and overall survival (P=0.04). Survivin expression was neither associated with clinicopathological characteristics nor with survival. However, survivin expression in the nucleus paralleled Aurora B expression (P=0.014). Aurora A expression was associated significantly with increased tumour grade (P=0.008). Multivariate analysis indicated that Aurora B was an independent predictor for LSCC-specific disease-free survival [hazard ratio (HR), 2.10; 95% confidence interval (95% CI), 1.25-3.52 (P=0.005)] and overall survival [HR, 1.91; 95% CI 1.01-3.34 (P=0.023)]. CONCLUSIONS: Aurora B may be a novel prognostic biomarker for LSCC and a potential therapeutic target in this type of tumour.

Idiopathic sclerosing orbital inflammation with intranasal extension.

INTRODUCTION: To report a case of idiopathic orbital sclerosing inflammation (ISOI) with intranasal extension. MATERIAL AND METHODS: The patient presented with a 6-month history of epiphora, upper eyelid swelling, ptosis and mild orbital pain. Ophthalmologic examination, CT, MRI and biopsy with surgical debulking were performed. RESULTS: MRI revealed a homogeneously enhancing diffuse right orbital mass in the inferonasal quadrant of the orbit, which extended to the nasal cavity up to inferior nasal concha, maxillary and ethmoid sinuses. Histological analysis showed dense collagenous tissue with sparse infiltration of mixed inflammatory cells. Inmunohistochemical analysis confirmed polyclonality. The diagnosis of idiopathic sclerosing orbital inflammation was made and 80 mg/day of oral prednisolone was prescribed. At last follow up, one year later, there was no clinical evidence of recurrent orbital disease. CONCLUSION: ISOI can present with extraorbital extension. Corticosteroids are a reasonable first-line treatment, until the pathogenesis is better understood.

Nanoscale positioning of inorganic nanoparticles using biological ferritin arrays fabricated by dip-pen nanolithography.

In this manuscript we demonstrate the spatially controlled immobilization of ferritin proteins by directly writing them on a wide range of substrates of technological interest. Optical and fluorescence microscopy, AFM and TOF-SIMS studies confirm the successful deposition of the protein on those surfaces. Control on nanostructure shape and size, by miniaturizing the dot-like features down to a 100 nm, demonstrates the particular capabilities of the DPN approach. Ultimately, this study gives the opportunity to design nanoparticle-based arrays regarding the growing interest in the use of nanoparticles as structural and functional elements for fabricating nanodevices. Herein, we demonstrate how the protein shell of ferritins can be removed by a simple heat-treatment process while maintaining the encapsulated inorganic nanoparticle intact on the same location of the nanoarray. As a result, this study establishes how direct-write DPN approach could give the opportunity to design not only protein-based nanoarrays but also nanoparticle-based nanoarrays with high-resolution and control.