Novel potential predictive markers of sunitinib outcomes in long-term responders versus primary refractory patients with metastatic clear-cell renal cell carcinoma

Background: Several potential predictive markers of efficacy of targeted agents in patients with metastatic renal cell carcinoma (mRCC) have been identified. Interindividual heterogeneity warrants further investigation. Patients and methods: Multicenter, observational, retrospective study in patients with clear-cell mRCC treated with sunitinib. Patients were classified in two groups: long-term responders (LR) (progression-free survival (PFS)=22 months and at least stable disease), and primary refractory (PR) (progressive disease within 3-months of sunitinib onset). Objectives were to compare baseline clinical factors in both populations and to correlate tumor expression of selected signaling pathways components with sunitinib PFS. Results: 123 patients were analyzed (97 LR, 26 PR). In the LR cohort, overall response rate was 79% and median duration of best response was 30 months. Median PFS and overall survival were 43.2 (95% confidence intervals[CI]:37.2-49.3) and 63.5 months (95%CI:55.1-71.9), respectively. At baseline PR patients had a significantly lower proportion of nephrectomies, higher lactate dehydrogenase and platelets levels, lower hemoglobin, shorter time to and higher presence of metastases, and increased Fuhrman grade. Higher levels of HEYL, HEY and HES1 were observed in LR, although only HEYL discriminated populations significantly (AUC[ROC]=0.704; cut-off=34.85). Increased levels of hsa-miR-27b, hsa-miR-23b and hsa-miR-628-5p were also associated with prolonged survival. No statistical significant associations between hsa-miR-23b or hsa-miR-27b and the expression of c-Met were found. Conclusions: Certain mRCC patients treated with sunitinib achieve extremely long-term responses. Favorable baseline hematology values and longer time to metastasis may predict longer PFS. HEYL, hsa-miR-27b, hsa-miR-23b and hsa-miR- 628-5p could be potentially used as biomarkers of sunitinib response

Differentiation of Human Embryonic Stem Cells to Regional Specific Neural Precursors in Chemically Defined Medium Conditions

Background: Human embryonic stem cells (hESC) provide a unique model to study early events in human development. The hESC-derived cells can potentially be used to replace or restore different tissues including neuronal that have been damaged by disease or injury. Methodology and Principal Findings: The cells of two different hESC lines were converted to neural rosettes using adherent and chemically defined conditions. The progenitor cells were exposed to retinoic acid (RA) or to human recombinant basic fibroblast growth factor (bFGF) in the late phase of the rosette formation. Exposing the progenitor cells to RA suppressed differentiation to rostral forebrain dopamine neural lineage and promoted that of spinal neural tissue including motor neurons. The functional characteristics of these differentiated neuronal precursors under both, rostral (bFGF) and caudalizing (RA) signals were confirmed by patch clamp analysis. Conclusions/Significance: These findings suggest that our differentiation protocol has the capacity to generate regionspecific and electrophysiologically active neurons under in vitro conditions without embryoid body formation, co-cultur

Microorganismos presentes en las uñas de las Asistentes Dentales de la Facultad de Odontología, UNAN-León, agosto 2007 - marzo 2008

UNAN-LeónUNAN-Leó

Un río puede ser un aula

Seleccionado en la convocatoria: Proyectos de innovación e investigación educativa de centros docentes de niveles no universitarios, Gobierno de Aragon 2012-2013Proyecto cuyo objetivo es el estudio de las orillas del río Ebro a través de la toma de datos bióticos y abióticos y destinado a los alumnos del tercer ciclo de educación primaria. Se diseñan diversas salidas a lo largo del curso que los alumnos recorrerán en bici, andando o coche. La metodología seguida se basa en la observación y posterior investigación. Se desarrollan actividades como: el estudio de los árboles y animales de la zona, la elaboración de planos, la visita a un invernadero, a una cooperativa de alfalfa y a una depuradora de aguas, el anillamiento de aves o el estudio de rocasGobierno de Aragón. Departamento de Educación, Universidad, Cultura y DeporteAragónDirección General de Política Educativa y Educación Permanente; Avenida Gómez Laguna, 25, planta 2ª; 50009 Zaragoza; Tel. +34976715416, Fax +34976715496ES

Psychological Impact and Risk of Suicide in Hospitalized COVID-19 Patients, During the Initial Stage of the Pandemic: A Cross-Sectional Study.

This study aimed to assess the psychological impact and risk of suicide in patients hospitalized for COVID-19. A cross-sectional study was conducted on a representative sample of patients hospitalized for COVID-19 at the "San Cecilio" University Hospital (Granada, Spain) between March and May 2020. Sociodemographic and clinical variables were collected. All participants were evaluated using the Gijon's Social-Familial Evaluation Scale to assess social problems, the Impact of Event Scale-6 and the Hospital Anxiety-Depression Scale to assess psychological impact, the Columbia Suicide Severity and Beck Hopelessness scales to assess risk of suicide, and the List of Threatening Experiences questionnaire to control for confounding bias. Thirty-six COVID-19 patients were evaluated. Of them, 33.3% had a significant psychological impact; 13.9% showed symptoms of anxiety, 13.9% showed symptoms of depression, and 47.2% showed symptoms of anxiety-depression. Moderate and severe risk of suicide were found in 75% and 2.8% of the patients, respectively. Suicidal ideation was observed in 16.7% and suicide behaviors in 5.6% of the patients. Psychological impact was associated with previous psychological treatment, a greater degree of functional dependency, and increased social-familial risk. In addition, the risk of suicide was mainly associated with active treatment of a psychiatric illness and active smoking. No significant correlation was found between psychological impact and risk of suicide. Psychological impact and risk of suicide were significant in patients admitted for COVID-19. Although the risk of suicide was not associated with increased psychological impact, both should be assessed, especially in patients at higher risk based on significantly associated factors

Activated spinal cord ependymal stem cells rescue neurological function

11 páginas,4 figuras, 1 tabla -- PAGS nros. 733-743Spinal cord injury (SCI) is a major cause of paralysis. Currently, there are no effective therapies to reverse this disabling condition. The presence of ependymal stem/progenitor cells (epSPCs) in the adult spinal cord suggests that endogenous stem cell-associated mechanisms might be exploited to repair spinal cord lesions. epSPC cells that proliferate after SCI are recruited by the injured zone, and can be modulated by innate and adaptive immune responses. Here we demonstrate that when epSPCs are cultured from rats with a SCI (ependymal stem/progenitor cells injury [epSPCi]), these cells proliferate 10 times faster in vitro than epSPC derived from control animals and display enhanced self renewal. Genetic profile analysis revealed an important influence of inflammation on signaling pathways in epSPCi after injury, including the upregulation of Jak/Stat and mitogen activated protein kinase pathways. Although neurospheres derived from either epSPCs or epSPCi differentiated efficiently to oligodendrocites and functional spinal motoneurons, a better yield of differentiated cells was consistently obtained from epSPCi cultures. Acute transplantation of undifferentiated epSPCi or the resulting oligodendrocyte precursor cells into a rat model of severe spinal cord contusion produced a significant recovery of motor activity 1 week after injury. These transplanted cells migrated long distances from the rostral and caudal regions of the transplant to the neurofilament-labeled axons in and around the lesion zone. Our findings demonstrate that modulation of endogenous epSPCs represents a viable cell-based strategy for restoring neuronal dysfunction in patients with spinal cord damage. STEM CELLS2009;27:733–743This research was supported by the Spanish Program of Regenerative Medicine Conselleria de Sanidad de la Generalidad Valenciana-Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias-Instituto de Salud Carlos III, Project RD06/0010/1006 and the Ministerio de Educación, Ciencia y Tecnología, grants SAF2007-63714 and SAF2007-63193, respectivelyPeer reviewe