Staining of Neuroendocrine Merkel Cells of Human Epidermis Using the Uranaffin Reaction

The uranaffin reaction (UR) stains neurosecretory (NS) granules of the neuroendocrine system under certain experimental conditions of staining and rinsing solutions. Human normal neuroendocrine (NE) Merkel cells stained using the UR exhibit a positive reaction in their NS granules, ribosomes, and nuclear chromatin. The average values of maximum granular diameter (GD = 69.1nm) and area (GA = 3637.8nm2) of NS granules measured in the adult NE Merkel cells stained with UR are significantly greater than those (GD = 61.4nm; GA = 2699.8nm2) seen in the fetal NE Merkel cells also stained with UR. No differences in form factor are found between fetal and adult NS granules. On different samples of human adult and fetal epidermis it is demonstrated that UR is a useful cytochemical marker for the NS granules of normal NE Merkel cells

Urban mobility data management: The OPTICITIES project and the Madrid standartization proposal

Urban mobility is an increasingly complex challenge for the cities, and involves many different aspects. An aspect central to the problem is the management of mobility data in the cities. The traditional approach has resulted in data silos implemented and mostly valid only for the city for which they were developed. The OPTICITIES project aims at providing a common framework for multimodal transport management and service provision in the urban environment. A thorough analysis of all the relevant aspects related to the urban data management will be performed in a number of European cities. Working on the idea of local implementations, an overall interoperability framework and local data management profiles of data formats and interfaces are being defined and tested. Working closely with ISO and CEN standardisation groups, it is expected that OPTICITIES will impact directly on reference standard drafts. Additionally, cities usually present also particularities that cannot be addressed exclusively from a technical point of view. The city and region of Madrid, Spain, has done a huge effort in order to integrate operators’ data in a common platform, but needs to consider legacy and new systems, and other factors. The OPTICITIES project aims to integrate all these factors into an implementation guidelines handbook that will allow any city, regardless of the currently used systems and applications, to address the deployment of advanced multimodal data management element

Oral health status in patients with moderate-severe and terminal renal failure

Objetivos. Evaluar el estado de salud oral de pacientes con insuficiencia renal crónica moderada/severa (IRC-MD) y con fallo renal terminal (FRT). Diseño. El grupo de estudio lo constituyeron 50 pacientes: 22 (44%) con IRC-MD y 28 (56%) con FRT incluidos en un programa de hemodiálisis. Los controles (n= 64) tenían características similares en relación al sexo, edad, peso y nivel educacional. Se realizó una exploración intraoral a todos los participantes recogiendo información acerca de: número de dientes cariados, ausentes y obturados; acúmulo de placa supragingival; acúmulo de cálculo; profundidad de bolsas periodontales en los dientes de Ramfjord; y pérdida de inserción. Resultados. No se detectaron diferencias significativas en los valores del índice CAO entre pacientes y controles. El número medio de dientes cariados fue inferior en los pacientes que en los controles (p= 0,052). En los pacientes, el nú- mero medio de dientes ausentes fue mayor que en los controles (p= 0,002). Había 12 pacientes y 7 controles totalmente edéntulos. El número medio de dientes obturados fue significativamente inferior en los pacientes que en los controles (p< 0,001). El acúmulo de placa supragingival y la pérdida de inserción fue significativamente mayor en los pacientes que en los controles (p= 0,006 y p< 0,001, respectivamente). No se encontraron diferencias significativas en relación al acúmulo de cálculo ni a la presencia de bolsas periodontales entre ambos grupos. El valor del índice CAO, el número medio de dientes cariados y el de obturados fue significativamente superior en los pacientes IRC-MD que en los pacientes FRT (p= 0,004, p= 0,030 y p= 0,006, respectivamente). Conclusión. Los pacientes con IRC tienen menor prevalencia de caries, más placa supragingival, más dientes con pérdida de inserción y más ausencias dentarias, que los controles sanos. La prevalencia de caries está condicionada por la severidad de la insuficiencia y/o por el tratamiento de hemodiálisis

Prognostic significance of cyclins A2, B1, D1, and E1 and CCND1 numerical aberrations in oral squamous cell carcinomas

We analysed the expression of cyclins A2, B1, D1, and E1 by immunohistochemistry and numerical aberrations in CCND1 gene by fluorescence in situ hybridization technique in 67 primary oral squamous cell carcinomas (OSCC). Cyclin A2 expression was observed in 54 (83.1%) tumours, cyclin D1 in 58 (89.2%), cyclin B1 in 39 (60%), and cyclin E in 21 (32.8%). CCND1 region analysis revealed 26 (43.3%) tumours with the presence of numerical aberrations which were correlated with cyclin D1 high expression (Rho = 0.48; p < 0 001). Twenty-nine (45.3%) tumours were classified as high proliferative tumours assessed by Ki-67 protein expression and correlated with tumours with high expression of cyclin A2 (Rho = 0.30; p = 0 016) and cyclin B1 (Rho = 0.37; p = 0 003). In multivariate analysis for an overall five-year survival (OS), we found an adverse independent prognostic value for cyclin A2 high expression (p = 0 031) and for advanced tumour stage (p < 0 001). Our results confirm that several cyclins are commonly expressed in OSCC. CCND1 gene is abnormal in more than one-third of the cases and is frequently associated with cyclin D1 high expression. Moreover, cyclin A2 high expression is an independent indicator of worse OS suggesting that this protein may serve as a reliable biological marker to identify high-risk subgroups with poor prognosis.This study was supported by a grant from the Fundación de Investigación Médica Mutua Madrileña (Spain) and Instituto de Salud Carlos III (FIS PI 061902). The authors also thank the Biobanco del Complejo Hospitalario Universitario de Santiago and IINFACTS in CESPU (BubOral CESPU 2017; MacrOral CESPU 2017)S

Primary systemic therapy in HER2-positive operable breast cancer using trastuzumab and chemotherapy: efficacy data, cardiotoxicity and long-term follow-up in 142 patients diagnosed from 2005 to 2016 at a single institution

Objective: The aim of this study was to evaluate the efficacy, cardiotoxicity profile and long-term benefits of neoadjuvant therapy in human epidermal growth factor receptor 2-positive operable breast cancer patients. Patients and methods: A total of 142 patients diagnosed from 2005 to 2016 were included in the study. The treatment consisted of a sequential regimen of taxanes and anthracyclines plus trastuzumab. The clinical and pathological responses were evaluated and correlated with clinical and biological factors. The cardiotoxicity profile and long-term benefits were analyzed. Results: The median age was 49 years, and 4%, 69% and 27% of patients had stage I, II and III breast cancer, respectively, while 10% had inflammatory breast cancer at diagnosis. Hormone receptor (HR) status was negative in 43%, and 62% had grade III breast cancer. The clinical complete response rate was 49% and 63% as assessed using ultrasound and magnetic resonance imaging, respectively, and this allowed a high rate of conservative surgery (66%). The pathological complete response (pCR) rate was 52%, and it was higher in HR-negative (64%) patients than in HR-positive (41%) patients and in grade III breast cancer (53%) patients than in grade I–II breast cancer (45%) patients. Patients who achieved pCR had longer disease-free survival and a trend toward improved overall survival. A total of 2% of patients showed a 10% decrease in left ventricular ejection fraction to <50% during treatment. All patients except one recovered after discontinuation of trastuzumab. Conclusion: A sequential regimen of taxanes and anthracyclines plus trastuzumab was effective, with high pCR rates and long-term benefit, and had a very good cardiotoxicity profile.S

Tuberculosis hepática aislada mimetizando un tumor hepático en un paciente en diálisis

Isolated tuberculosis (TB) of the liver is a rare form of extrapulmonary presentation of the disease, even in countries where tuberculosis in a public health concern. Given its low incidence, diagnosis is complex since the specificity of the clinical picture and microbiological studies have limited detection of the presence of Mycobacterium tuberculosis. Extrapulmonary forms of TB are clinical entities that may be precipitated by conditions linked to immunosuppression such as chronic kidney disease (CKD) particularly in the last stages.La tuberculosis (TB) hepática aislada es una forma rara de TB extrapulmonar, incluso en países donde la tuberculosis se comporta como un problema de salud pública. Su diagnóstico es complejo dada la baja especificidad del cuadro clínico y al limitado rendimiento diagnóstico de los estudios microbiológicos para establecer la presencia del Mycobacterium tuberculosis. Presentamos el caso de un varón de 65 años con enfermedad renal crónica grado 5 en terapia de reemplazo renal con hemodiálisis quien presentó cuadro clínico de 3 días de evolución asociado a dolor abdominal y anorexia. En la ecografía se evidenció lesiones hepáticas hipoecoicas, corroboradas por tomografía de ab domen con hallazgos sugestivos de neoplasia hepática secundaria sin establecerse un origen primario. La biopsia de hígado finalmente condujo al diagnóstico de tuberculosis hepática sin encontrarse compromiso pulmonar o extrapulmonar adicional. Concluimos que las formas extrapulmonares de TB son entidades clínicas que pueden estar precipitadas por condiciones ligadas a inmunosupresión como es la enfermedad renal crónica

Detoxifying antitumoral drugs via nanoconjugation: the case of gold nanoparticles and cisplatin

Nanoparticles (NPs) have emerged as a potential tool to improve cancer treatment. Among the proposed uses in imaging and therapy, their use as a drug delivery scaffold has been extensively highlighted. However, there are still some controversial points which need a deeper understanding before clinical application can occur. Here the use of gold nanoparticles (AuNPs) to detoxify the antitumoral agent cisplatin, linked to a nanoparticle via a pH-sensitive coordination bond for endosomal release, is presented. The NP conjugate design has important effects on pharmacokinetics, conjugate evolution and biodistribution and results in an absence of observed toxicity. Besides, AuNPs present unique opportunities as drug delivery scaffolds due to their size and surface tunability. Here we show that cisplatin-induced toxicity is clearly reduced without affecting the therapeutic benefits in mice models. The NPs not only act as carriers, but also protect the drug from deactivation by plasma proteins until conjugates are internalized in cells and cisplatin is released. Additionally, the possibility to track the drug (Pt) and vehicle (Au) separately as a function of organ and time enables a better understanding of how nanocarriers are processed by the organism.The authors acknowledge financial support from the grants “Plan Nacional” (MAT2009-14734-C02-01 and MAT2009-14734-C02-02) and NANOBIOMED-CONSOLIDER (CSD2006-00012) from the Spanish Government. Also grants VALTEC09-2-0085, VALTEC09-2-0089, and 2009-SGR-776 from the Catalan GovernmentS

Proyecto Sost-Wine: hacia una nueva forma de estimar el agua en la vid

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Seguimiento del Grado en Óptica y Optometría

En el marco del proyecto de Redes de Investigación en Docencia Universitaria 2013-14 de la Universidad de Alicante se creó una red de trabajo formada por los profesores coordinadores de semestre del Grado en Óptica y Optometría y dos alumnos. Dado que durante el curso académico 2013-14 ha tenido lugar la implantación del último curso del Grado en Óptica y Optometría, el objetivo principal de esta red ha sido la realización de un análisis de la implantación del título así como el estudio del diseño y desarrollo del Trabajo Fin de Grado y del programa de Prácticas Externas. Para ello se han recogido las sugerencias y propuestas realizadas a través de las comisiones de semestres, de la comisión de garantía de calidad y de reuniones con el alumnado, con el fin de optimizar el funcionamiento del título, tanto en la distribución de contenidos, como en las metodologías docentes y de evaluación de las distintas materias que componen el plan de estudios

Molecular Profiling of Circulating Tumour Cells Identifies Notch1 as a Principal Regulator in Advanced Non-Small Cell Lung Cancer

Knowledge on the molecular mechanisms underlying metastasis colonization in Non-Small Cell Lung Cancer (NSCLC) remains incomplete. A complete overview integrating driver mutations, primary tumour heterogeneity and overt metastasis lacks the dynamic contribution of disseminating metastatic cells due to the inaccessibility to the molecular profiling of Circulating Tumour Cells (CTCs). By combining immunoisolation and whole genome amplification, we performed a global gene expression analysis of EpCAM positive CTCs from advanced NSCLC patients. We identified an EpCAM+ CTC-specific expression profile in NSCLC patients mostly associated with cellular movement, cell adhesion and cell-to-cell signalling mediated by PI3K/AKT, ERK1/2 and NF-kB pathways. NOTCH1 emerged as a driver connecting active signalling pathways, with a reduced number of related candidate genes (NOTCH1, PTP4A3, LGALS3 and ITGB3) being further validated by RT-qPCR on an independent cohort of NSCLC patients. In addition, these markers demonstrated high prognostic value for Progression-Free Survival (PFS). In conclusion, molecular characterization of EpCAM+ CTCs from advanced NSCLC patients provided with highly specific biomarkers with potential applicability as a “liquid biopsy” for monitoring of NSCLC patients and confirmed NOTCH1 as a potential therapeutic target to block lung cancer dissemination.This work was funded by InveNNta (Innovation in Nanomedicine); Operational Programme for Cross-border Cooperation: Spain-Portugal (POCTEP) and European Regional Development Fund (ERDF). Javier Mariscal is recipient of a fellowship from Escola de Doutoramento Internacional Campus Vida of the University of Santiago de Compostela. Laura Muinelo-Romay is supported by ISCIII as Responsible of the Liquid Biopsy Analysis UnitS