Nonsingular charged black holes \`{a} la Palatini

We argue that the quantum nature of matter and gravity should lead to a discretization of the allowed states of the matter confined in the interior of black holes. To support and illustrate this idea, we consider a quadratic extension of General Relativity formulated \`{a} la Palatini and show that nonrotating, electrically charged black holes develop a compact core at the Planck density which is nonsingular if the mass spectrum satisfies a certain discreteness condition. We also find that the area of the core is proportional to the number of charges times the Planck area.Comment: 10 single column page

Autologous and Allogeneic Stem Cell Transplantation for Treatment of Crohn’s Fistulae

Up to 20% of patients with Crohn’s disease (CD) may have perianal fistula disease. Classically, surgery has played an important role; in recent years, medical treatment has taken a leading role. Immunosuppressants and biological trea tments have proven beneficial in many patients, but still, the percentage of patients who do not respond remains significant. In this scenario, cell therapy is envisaged as an effective alternative to surgery. The promising preclinical and clinical data that we review below suggest that cell therapy could represent a major advance in the clinical management of this difficult problem

Optical Spectroscopy of nearby type1-LINERs

We present the highlights from our recent study of 22 local (z$<$0.025) type-1 LINERs from the Palomar Survey, on the basis of optical long-slit spectroscopic observations taken with TWIN/CAHA, ALFOSC/NOT and HST/STIS (Cazzoli et al. 2018). Our goals were threefold: (a) explore the AGN- nature of these LINERs by studying the broad (BLR-originated) H$\alpha$ component; (b) derive a reliable interpretation for the multiple narrow components of emission lines by studying their kinematics and ionisation mechanism (via standard BPTs); (c) probe the neutral gas in the nuclei of these LINERs for the first time. Hence, kinematics and fluxes of a set of emission lines, from H$\beta$ to [SII], and the NaD doublet in absorption have been modelled and measured, after the subtraction of the underlying light from the stellar component.Comment: Proceedings of the IAU Symposium 356, 'Nuclear activity in galaxies across cosmic time'. Based on Cazzoli et al. 2018, MNRAS, 480, 1106 available at https://academic.oup.com/mnras/article/480/1/1106/505038

Aislamiento y cultivo de células osteoblásticas: Interés para la investigación en cirugía ortopédica y traumatología

Describimos un método de aislamiento y caracterización de células osteoblásticas procedentes de la superficie de trabéculas óseas de explantes obtenidos de metafisis de fémures y tibias de conejo y de cabezas femorales humanas de pacientes sometidos a cirugía protésica de cadera. Después de eliminar las células de la médula ósea de los explantes, estos se despositaron sobre dos tipos de mallas, de 80 y 100 µm., obteniéndose un cultivo en monocarpa que se mostró confluente a partir de los 20 días. La población celular aislada presentó un fenotipo osteoblástico utilizando métodos colorimétricos para determinación de la actividad de fosfatasa alcalina (FA) y morfológicos por medio de la observación con microscopía electrónica de barrido. Las células cultivadas exhibieron una morfología diferente según el grado de confluencia de cultivo, siendo en todo momento positivas las sucesivas determinaciones colorimétricas de FA realizadas a lo largo de la experiencia. Consideramos el método de gran interés en investigación en ortopédica, pues permite el estudio de comportamiento de estas células cuando están sometidas a cualquier tipo de estímulo externo, así como cuando se enfrentan a nuevas generaciones de biomateriales, etc.We describe a method of isolation and characterization of osteoblastic cells taken from the surface of bone trabeculae of explants obtained from femur and tibia metaphysis in rabbits and human femoral head in patients undergoing orthopaedic surgery. Afther removing the cells from the bone marrow of explants, they were placed over two mesh, 80 and 100 µmn, obtaining then a culture in monolayer which showed to be confluent after 20 days. The isolated cell population showed an osteoblastic phenotype using colourmetric methods to determinate the alkaline phosphatase (AF) activity and morphologic methods by means of scanning. The cultivated cell showed a different morphology according to the degree of confluence of the culture, being always positive the sucesive colourmetric determinations of AF along the experiment. We consider the method of a great interest for orthopaedic investigations, since it allows the study of the behaviour of these cells when they are subjet to different types of external stimulus as well as meet they the new generations of biomaterials

Comment on 'Distinct clinical outcomes of two CIMP-positive colorectal cancer subtypes based on a revised CIMP classification system'

This work was funded by Projects PI13/01741, PI13/01273, PI16/01920 and PI16/01650 from the Spanish Ministry of Health and Consumer Affairs and FEDER, and Mutua Madrileña Foundation (2012-0036), and was approved by the Ethics Committee of our Institution.Peer Reviewe

A clinico-pathological and molecular analysis reveals differences between solitary (early and late-onset) and synchronous rectal cancer

Rectal cancer (RC) appears to behave differently compared with colon cancer. We aimed to analyze existence of different subtypes of RC depending on distinct features (age of onset and the presence of synchronous primary malignant neoplasms). We compared the clinicopathological, familial and molecular features of three different populations diagnosed with RC (early-onset RC [EORC], late-onset RC, and synchronous RC [SRC]). Eighty-five RCs were identified and were evaluated according to their microsatellite instability, CpG Island Methylator Phenotype (CIMP) and chromosomal instability, as assessed by Next Generation Sequencing and microarray-based comparative genomic hybridization approaches. The results were subjected to cluster analysis. SRCs displayed the most specific characteristics including a trend for the development of multiple malignant neoplasms, a greater proportion of CIMP-High tumors (75%) and more frequent genomic alterations. These findings were confirmed by a clustering analysis that stratified RCs according to their genomic alterations. We also found that EORCs exhibited their own features including an important familial cancer component and a remarkable rate of mutations in TP53 (53%). Together, heterogeneity in RC characteristics by age of disease-onset and SRC warrants further study to optimize tailored prevention, detection and intervention strategies—particularly among young adults.This work was funded by the Spanish Ministry of Health and Consumer Affairs and FEDER, Grant number PI16/01650 to José Perea, PI16/01920 to Rogelio González-Sarmiento, and PI14/00459 to Miguel Uriost

The AGN nature of LINER nuclear sources

Properties of LINERs

Biocompatibility and osseointegration study of new prosthetic materials

Objetivos Los implantes óseos son utilizados cada vez con mayor frecuencia en la práctica clínica y, entre los materiales, el Ti o sus aleaciones son los de mejor rendimiento por sus propiedades fisicoquímicas. Aleaciones como TiNbTa han demostrado mejorar las características biomecánicas del Ti puro comercial (c.p.), sin embargo, su capacidad osteointegradora necesita ser evaluada. El objetivo del presente estudio fue valorar la citotoxicidad y la capacidad de adhesión, proliferación y diferenciación de células osteoblásticas en cultivo, influida por discos de material TiNbTa frente a Ti c.p. Material y métodos Analizamos a los 4 y 7 días del cultivo la línea celular MC3T3, la viabilidad celular (AlamarBlue Cell Viability Reagent. Invitrogen, España), así como la proliferación y diferenciación celular (actividad de fosfatasa alcalina (ALP) y microscopía electrónica de barrido (Fijación para SEM). Se realizó la prueba t de Student para determinar diferencias estadísticamente significativas entre los dos grupos de discos de estudio. Resultados Los resultados obtenidos demuestran muy buena viabilidad celular durante el periodo de estudio, sin diferencias significativas para ambos materiales. Así mismo, detectamos una caída en los niveles de ALP que fue significativa para ambos componentes entre los días 4 y 7 del estudio (p<0,05). Las imágenes de microscopía electrónica revelaron buena capacidad de adhesión al material, así como diferenciación celular frente a ambos tipos de discos. Conclusiones La aleación de TiNbTa como material para implantes óseos cuenta con una buena capacidad osteointegradora, además de resolver problemas de biomecánica que presenta el titanio puro como componente.Objetive Bone implants are increasingly used in clinical practice and, among the materials, Ti or its alloys are offer the best performance given their physicochemical properties. Alloys such as TiNbTa have been shown to improve the biomechanical characteristics of commercial pure Ti (c.p.), however, its osseointegration capacity needs to be evaluated. The objective of the present study was to assess the cytotoxicity and the adhesion, proliferation and differentiation capacity of osteoblastic cells in culture, influenced by discs of TiNbTa material versus Ti c.p. Material and methods At 4 and 7 days after culture, we analyzed the MC3T3 cell line, cell viability (AlamarBlue Cell Viability Reagent. Invitrogen, Spain), as well as cell proliferation and differentiation (alkaline phosphatase activity (ALP) and scanning electron microscopy (Fixation for SEM) Student's t test was performed to determine statistically significant differences between the two groups of study discs. Results The results obtained show very good cell viability during the study period, with no significant differences for both materials. Likewise, we detected a drop in ALP levels that was significant for both components between days 4 and 7 of the study (p <0.05). Electron microscopy images revealed good adhesion capacity to the material, as well as cell differentiation against both types of discs. Conclusions The TiNbTa alloy as a material for bone implants offers good osseointegrative capacity, in addition to solving biomechanical problems that pure titanium presents as a component

Chronic cannabinoid administration to periadolescent rats modulates the metabolic response to acute cocaine in the adult brain

Purpose: To analyze brain metabolic response to acute cocaine in male and female Wistar rats with or without a history of cannabinoid exposure during periadolescence. Procedures: The synthetic cannabinoid agonist CP 55,940 (CP) or its vehicle (VH), were administered to male and female rats during periadolescence. When these animals reached adulthood, saline and cocaine-induced changes in 2-deoxy-2-[18F]fluoro D glucose (FDG) uptake were studied by positron emission tomography. Results: The baseline (post-saline) metabolism in the septal nuclei was higher in CP-females than in VH-females, although septal metabolism was lower in CP-females after cocaine, reaching similar values to those of VH-females at baseline. Cocaine did not affect metabolism in VH-females. Periadolescent cannabinoid treatment did not influence baseline metabolism in males although cocaine reduced the FDG uptake in the dorsal striatum of males that received the VH but not CP. Conclusions: These results suggest that cannabinoids during periadolescence modify baseline and cocaine-evoked brain metabolism in a sex-dependent manner. In the case of CP-females, the involvement of septal metabolic alterations in their susceptibility to the rewarding effects of cocaine should be further investigated.This work was supported by grants from the Ministerio de Educación y Ciencia (Grants nº SAF2004-08148 and SAF2007-064890); Ministerio de Sanidad y Consumo (Grants RD06/ 00170029 of Instituto de Salud Carlos III, PNSD 2004 2007 and 2008 2010); Dirección General de Investigación de la Comunidad de Madrid (Grant S-SAL/0261/2006, I+D CANNAB-CM Consortium); and UNED (Plan de Promoción de la Investigación) to EA, and grants from the “Ministerio de Ciencia y Tecnología” (TEC2004-07052-C02-01/TCM), “Ministerio de Sanidad y Consumo” (CIBER CB06/01/0079, PNSD 2007 2010, FIS CP08/00017), “Ministerio de Industria” (CENIT program) and “Fundación de Investigación Médica Mutua Madrileña” (2007 2010 and 2008 2011) to MD.Publicad

Cimp-Positive Status is More Representative in Multiple Colorectal Cancers than in Unique Primary Colorectal Cancers

We thank the Tumor Registry of the Pathology Department of the 12 de Octubre University Hospital for providing the paraffin-embedded tissues, and Ron Hartong for his help with the English revision of this manuscript. This work was funded by Projects PI10/00683 and PI16/01650 to J.P, and PI16/01920 to R.G.S, from the Spanish Ministry of Health and Consumer Affairs and FEDER, and by Project 2012-0036 from the Mutua Madrileña Foundation. This work was supported by R01 (CA72851, CA181572, CA184792, CA202797) and U01 (CA187956, CA214254) grants from the National Cancer Institute, NIH; RP140784 from the CancerPrevention Research Institute of Texas; grants from the Baylor Foundation and Baylor Scott & White Research Institute, Dallas, TX, USA to AG.Colorectal cancer (CRC) with CpG island methylator phenotype (CIMP) is recognized as a subgroup of CRC that shows association with particular genetic defects and patient outcomes. We analyzed CIMP status of 229 individuals with CRC using an eight-marker panel (CACNA1G, CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1); CIMP-(+) tumors were defined as having ≥ 5 methylated markers. Patients were divided into individuals who developed a "unique" CRC, which were subclassified into early-onset CRC (EOCRC) and late-onset CRC (LOCRC), and patients with multiple primary CRCs subclassified into synchronous CRC (SCRC) and metachronous CRC (MCRC). We found 9 (15.2%) CIMP-(+) EOCRC patients related with the proximal colon (p = 0.008), and 19 (26.8%) CIMP-(+) LOCRC patients associated with tumor differentiation (p = 0.045), MSI status (p = 0.021) and BRAF mutation (p = 0.001). Thirty-five (64.8%) SCRC patients had at least one CIMP-(+) tumor and 20 (44.4%) MCRC patients presented their first tumor as CIMP-(+). Thirty-nine (72.2%) SCRC patients showed concordant CIMP status in their simultaneous tumors. The differences in CIMP-(+) frequency between groups may reflect the importance of taking into account several criteria for the development of multiple primary neoplasms. Additionally, the concordance between synchronous tumors suggests CIMP status is generally maintained in SCRC patients.S