Early Diagnosis of Oral Cancer: A Complex Polyhedral Problem with a Difficult Solution

Oral and oropharyngeal cancers are a growing problem, accounting for 377,713 and 98,412 new cases per year all over the world and 177,757 and 48,143 deaths annually, respectively. Despite the substantial improvement in diagnostic procedures and treatment techniques in recent years, the mortality rate has not decreased substantially in the last 40 years, which is still close to 50% of cases. The major cause responsible for this high mortality is associated with the high percentage of oral cancers diagnosed in advanced stages (stages III and IV) where the treatment harbors poor efficacy, resulting in challenges, mutilations, or disability. The main reason for cancer to be diagnosed at an advanced stage is a diagnostic delay, so it is critical to reduce this delay in order to improve the prognosis of patients suffering from oral cancer. The causes of oral cancer diagnostic delay are complex and concern patients, healthcare professionals, and healthcare services. In this manuscript, oral cancer diagnostic delay is critically reviewed based on current evidence, as well as their major causes, main problems, and potential improvement strategiesResearch group CTS-392 (Plan Andaluz de Investigación, Junta de Andalucía, Spain

Prognostic and Clinicopathological Significance of CCND1/Cyclin D1 Upregulation in Melanomas: A Systematic Review and Comprehensive Meta-Analysis

We would like to thank the research group CTS-392 (Plan Andaluz de Investigación, Junta de Andalucía, Spain).Simple Summary The incidence of cutaneous melanoma is increasing worldwide, currently responsible for 287,723 new cases and 60,712 deaths per year (GLOBOCAN, IARC, WHO). It should be also highlighted that some less frequent subtypes of melanomas-i.e., acral, uveal, and mucous melanoma-are responsible for significant morbidity associated with metastasis, responding typically worse to newer therapies. Therefore, new biomarkers are needed to improve the prognosis in individual patients. In this sense, the present study showed that CCND1/cyclin D1 upregulation is a common molecular oncogenic alteration in melanomas that probably favors the growth and expansion on cutaneous primary melanomas. Furthermore, immunohistochemical cyclin D1 overexpression strongly predicted a higher Breslow thickness, currently considered the most relevant prognostic factor in individual patients with melanomas. Finally, special attention should be paid to the CCND1/cyclin D1 complex in mucosal melanomas, whose upregulation was strikingly altered. Our objective was to evaluate the prognostic and clinicopathological significance of cyclin D1 (CD1) overexpression/CCND1 amplification in melanomas. We searched studies published before September 2019 (PubMed, Embase, Web of Science, Scopus). We evaluated the quality of the studies included (QUIPS tool). The impact of CD1 overexpression/CCND1 amplification on overall survival and relevant clinicopathological characteristic were meta-analyzed. We performed heterogeneity, sensitivity, small-study effects, and subgroup analyses. Forty-one studies and 3451 patients met inclusion criteria. Qualitative evaluation demonstrated that not all studies were performed with the same rigor, finding the greatest risk of bias in the study confounding domain. Quantitative evaluation showed that immunohistochemical CD1 overexpression had a statistical association with Breslow thickness (p = 0.007; OR = 2.09,95% CI = 1.23-3.57), significantly higher frequency of CCND1/cyclin D1 abnormalities has been observed in the primary tumor compared to distant metastases (p = 0.004), revealed also by immunohistochemical overexpression of the protein (p < 0.001; OR = 0.53,95% CI = 0.40-0.71), while the CCND1 gene amplification does not show association (p = 0.43); while gene amplification, on the contrary, appeared more frequently in distant metastases (p = 0.04; OR = 1.70,95% CI = 1.01-2.85) and not in the primary tumor. In conclusion, CCND1/cyclin D1 upregulation is a common molecular oncogenic alteration in melanomas that probably favors the growth and expansion of the primary tumor. This upregulation is mainly consequence to the overexpression of the cyclin D1 protein, and not to gene amplification

Dysplasia in oral lichen planus: relevance, controversies and challenges. A position paper

Background: Patients with oral lichen planus (OLP) have an increased risk of oral cancer. For this reason, OLP is classified as an oral potentially malignant disorder. However, the precise personal (or individual) risk is unknown. Recent meta-analytical studies have reported that dysplastic OLP may transform to cancer in around 6% of cases, while the rate of transformation is lower (<1.5%) in non-dysplastic cases. The presence of epithelial dysplasia has emerged as the most powerful indicator for assessing cancer risk in oral potentially malignant disorders in routine practice. However, the general acceptance of epithelial dysplasia as an accompanying histologic feature in OLP is subject to great controversy. Many pathologists consider the presence of dysplasia as a criterion to exclude OLP when routinely reporting on this disease. This practice, widespread among oral pathology professionals, has resulted in the underestimation of the potential for malignancy of OLP. Material and Methods: A review of the literature was carried out in order to critically analyze the relevance, controversies and challenges encountered across the diagnosis of epithelial dysplasia in OLP. Results: 12 studies have been published examining dysplastic changes in OLP, reporting figures ranging from 0.54% to 25% of cases with dysplasia in the first diagnostic biopsy. The diagnosis of dysplasia in the OLP poses an additional difficulty due to the fact that the affected oral epithelium per se develops changes related to autoimmune aggression. Among the most frequent histological features of OLP that develops dysplasia are basal cell hyperplasia with basaloid appearance, loss of basal cells polarity, cellular and nuclear pleomorphism and irregular stratification. Conclusions: Epithelial dysplasia should not be considered an exclusion criterion for OLP; its evaluation requires experienced pathologists in this field

Control de acceso en redes sociales web

Proceeding of: XII Reunión Española sobre Criptología y Seguridad de la Información (RECSI 2012), Donostia-San Sebastián, Spain, 4-7 sept. 2012Recientemente, motivados por la expansión de internet y la aparición de las Redes Sociales Web (RSW), han surgido gran cantidad de problemas y retos asociados con la privacidad. Uno de los problemas principales es el diseño y la implementación de sistemas que posibiliten a los usuarios la gestión del control de acceso. A este respecto, pero en el contexto de las RSW, se han identificado una serie de requisitos. Sin embargo, en la literatura, los trabajos existentes sólo satisfacen parcial o completamente algunos de ellos. En este artículo, se propone primero un modelo de control de acceso, SoNeUCONABC, el cual extiende el modelo UCONABC, junto con la especificación de un mecanismo que lo implementa. En segundo lugar, se proporcionan directrices para el establecimiento de mecanismos que, desplegados sobre SoNeUCONABC, satisfagan todos los requisitos. PalabrasNo publicad

Climatology of new particle formation at Izaña mountain GAW observatory in the subtropical North Atlantic

A climatology of new particle formation (NPF) events at high altitude in the subtropical North Atlantic is presented. A 4-year data set (June 2008–June 2012), which includes number size distributions (10–600 nm), reactive gases (SO2, NOx, and O3), several components of solar radiation and meteorological parameters, measured at Izaña Global Atmosphere Watch (GAW) observatory (2373 m above sea level; Tenerife, Canary Islands) was analysed. NPF is associated with the transport of gaseous precursors from the boundary layer by orographic buoyant upward flows that perturb the low free troposphere during daytime. On average, 30% of the days contained an NPF event.This study was performed within the context of several projects, supported by the Ministry of Economy and Competitiveness of Spain (POLLINDUST, CGL2011-26259), REDMAAS (CGL2011- 15008-E) and GRACCIE (CSD2007-00067) and by the European Union (FP7, ACTRIS, grant contract: 262254)

Characterization of new particles formation events at Izaña Mountain Observatory (Tenerife, Canary Islands): formation, growth rates and influencing atmospheric parameters

Comunicación presentada en: 2012 European Aerosol Conference (EAC-2012), B-WG01S2P30, celebrada del 2 al 7 de septiembre de 2012 en Granada.This study was performed within the context of projects REDMAAS (CGL2011-15008-E) and POLLINDUST (CGL2011-26259)

Protocolo de creación de evidencias en entornos vehiculares

V Congreso Iberoamericano de Seguridad Informática, CIBSI'09 (Montevideo, Uruguay, 16 al 18 de Noviembre)Las redes vehiculares son un novedoso escenario de comunicación. Estas redes permiten el diálogo entre vehículos, y de estos con la infraestructura. Gracias a estas redes se puede proporcionar más información y nuevos servicios a conductores y pasajeros. Uno de esos nuevos servicios es la creación de evidencias sobre el comportamiento de un vehículo. Esto será útil, por ejemplo, para la correcta determinación de responsabilidad en un accidente o para justificar un comportamiento adecuado ante una sanción recibida. Utilizando las redes vehiculares se puede obtener la descripción de ese comportamiento a través de los vehículos del entorno. Con ello se impide que el propio vehículo describa su actuación de una forma modificada acorde con sus intereses. Para abordar este nuevo servicio es necesario garantizar la seguridad de la información intercambiada. En este trabajo se presenta un protocolo de creación de evidencias sobre el comportamiento de un vehículo, obteniendo los datos desde los cercanos. Se incluye el protocolo de verificación de las evidencias, así como el análisis de seguridad de la propuesta.Este trabajo ha sido parcialmente financiado por el Ministerio de Ciencia e Innovacion (España), dentro del Plan Nac. de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica 2008-2011, contrato TIN2009-13461 (proy. E-SAVE).Publicad

Genomic analysis reveals the major driving forces of bacterial life in the rhizosphere

A global analysis of Pseudomonas putida gene expression performed during the interaction with maize roots revealed how a bacterial population adjusts its genetic program to the specific conditions of this lifestyle

Genetic Dissection of the Regulatory Network Associated with High c-di-GMP Levels in Pseudomonas putida KT2440

Most bacteria grow in nature forming multicellular structures named biofilms. The bacterial second messenger cyclic diguanosine monophosphate (c-di-GMP) is a key player in the regulation of the transition from planktonic to sessile lifestyles and this regulation is crucial in the development of biofilms. In Pseudomonas putida KT2440, Rup4959, a multidomain response regulator with diguanylate cyclase activity, when overexpressed causes an increment in the intracellular levels of c-di-GMP that gives rise to a pleiotropic phenotype consisting of increased biofilm formation and crinkly colony morphology. In a broad genomic screen we have isolated mutant derivatives that lose the crinkly morphology, designed as cfc (crinkle free colony). A total of 19 different genes have been identified as being related with the emergence of the cfc phenotype either because the expression or functionality of Rup4959 is compromised, or due to a lack of transduction of the c-di-GMP signal to downstream elements involved in the acquisition of the phenotype. Discernment between these possibilities was investigated by using a c-di-GMP biosensor and by HPLC-MS quantification of the second messenger. Interestingly five of the identified genes encode proteins with AAA+ ATPase domain. Among the bacterial determinants found in this screen are the global transcriptional regulators GacA, AlgU and FleQ and two enzymes involved in the arginine biosynthesis pathway. We present evidences that this pathway seems to be an important element to both the availability of the free pool of the second messenger c-di-GMP and to its further transduction as a signal for biosynthesis of biopolimers. In addition we have identified an uncharacterized hybrid sensor histidine kinase whose phosphoaceptor conserved histidine residue has been shown in this work to be required for in vivo activation of the orphan response regulator Rup4959, which suggests these two elements constitute a two-component phosphorelay system.This work was supported by grants BFU2010-17946 and BFU2013-43469-P from Plan Nacional de I+D+I (Spanish Government) and by EDFR funds. OH-R was supported by a FPI fellowship and LB-M by predoctoral fund from Junta de Andalucía. MAM was supported by the Postdoctoral Juan de la Cierva Spanish Research Program (JCI-2012-11815).Peer reviewedPeer Reviewe