Immune-Checkpoint Inhibitors in B-Cell Lymphoma

For years, immunotherapy has been considered a viable and attractive treatment option for patients with cancer. Among the immunotherapy arsenal, the targeting of intratumoral immune cells by immune-checkpoint inhibitory agents has recently revolutionised the treatment of several subtypes of tumours. These approaches, aimed at restoring an effective antitumour immunity, rapidly reached the market thanks to the simultaneous identification of inhibitory signals that dampen an effective antitumor response in a large variety of neoplastic cells and the clinical development of monoclonal antibodies targeting checkpoint receptors. Leading therapies in solid tumours are mainly focused on the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) pathways. These approaches have found a promising testing ground in both Hodgkin lymphoma and non-Hodgkin lymphoma, mainly because, in these diseases, the malignant cells interact with the immune system and commonly provide signals that regulate immune function. Although several trials have already demonstrated evidence of therapeutic activity with some checkpoint inhibitors in lymphoma, many of the immunologic lessons learned from solid tumours may not directly translate to lymphoid malignancies. In this sense, the mechanisms of effective antitumor responses are different between the different lymphoma subtypes, while the reasons for this substantial difference remain partially unknown. This review will discuss the current advances of immune-checkpoint blockade therapies in B-cell lymphoma and build a projection of how the field may evolve in the near future. In particular, we will analyse the current strategies being evaluated both preclinically and clinically, with the aim of fostering the use of immune-checkpoint inhibitors in lymphoma, including combination approaches with chemotherapeutics, biological agents and/or different immunologic therapies

Cytotoxicity of the mycotoxins deoxynivalenol and ochratoxin A on Caco-2 cell line in presence of resveratrol

Exposure to mycotoxins through dietary food intake involves a highly complex scenario where co-contamination of different mycotoxins has been frequently demonstrated. On the other hand, the effect of the interaction of mycotoxins with other generally considered beneficial food components, as the antioxidants, has been scarcely studied. The main goal of the present work was to assess the cytotoxic effects on Caco-2 cells of the mycotoxins deoxynivalenol (DON) and ochratoxin A (OTA), alone or combined, and to explore potential protective effects of resveratrol (RES), an antioxidant frequently found in wine. In parallel, reactive oxygen species (ROS) production has also been studied as a first approach to understand the underlying mechanism of cytotoxicity. Results indicate a higher toxic effect of the mycotoxins when they are co-exposed. This increase in cytotoxicity was not accompanied by an increase in ROS production. The co-exposure of OTA or DON with RES did not result in a decrease in cytotoxicity; on the contrary, it resulted in increased cytotoxicity not associated with an increase in ROS production.The authors are grateful to the CYTED Action 109AC0371, to the INIA project (RTA 2012-00053-00-00) as well as the Spanish (Project AGL2011-24862) and Catalonian (XaRTA-Reference Network on Food Technology) Governments for their financial support. C.A. González-Arias thanks the Secretaria de Universitats i Recerca del Departament de Economia i Coneixement of the Generalitat de Catalunya for the pre-doctoral grant

Security Guidelines for the Development of Accessible Web Applications through the implementation of intelligent systems

Due to the significant increase in threats, attacks and vulnerabilities that affect the Web in recent years has resulted the development and implementation of tools and methods to ensure security measures in the privacy, confidentiality and data integrity of users and businesses. Under certain circumstances, despite the implementation of these tools do not always get the flow of information which is passed in a secure manner. Many of these security tools and methods cannot be accessed by people who have disabilities or assistive technologies which enable people to access the Web efficiently. Among these security tools that are not accessible are the virtual keyboard, the CAPTCHA and other technologies that help to some extent to ensure safety on the Internet and are used in certain measures to combat malicious code and attacks that have been increased in recent times on the Web. Through the implementation of intelligent systems can detect, recover and receive information on the characteristics and properties of the different tools and hardware devices or software with which the user is accessing a web application and through analysis and interpretation of these intelligent systems can infer and automatically adjust the characteristics necessary to have these tools to be accessible by anyone regardless of disability or navigation context. This paper defines a set of guidelines and specific features that should have the security tools and methods to ensure the Web accessibility through the implementation of intelligent systems

Cryo-EM structure of a helicase loading intermediate containing ORC-Cdc6-Cdt1-MCM2-7 bound to DNA

In eukaryotes, the Cdt1-bound replicative helicase core MCM2-7 is loaded onto DNA by the ORC-Cdc6 ATPase to form a prereplicative complex (pre-RC) with an MCM2-7 double hexamer encircling DNA. Using purified components in the presence of ATP-γS, we have captured in vitro an intermediate in pre-RC assembly that contains a complex between the ORC-Cdc6 and Cdt1-MCM2-7 heteroheptamers called the OCCM. Cryo-EM studies of this 14-subunit complex reveal that the two separate heptameric complexes are engaged extensively, with the ORC-Cdc6 N-terminal AAA+ domains latching onto the C-terminal AAA+ motor domains of the MCM2-7 hexamer. The conformation of ORC-Cdc6 undergoes a concerted change into a right-handed spiral with helical symmetry that is identical to that of the DNA double helix. The resulting ORC-Cdc6 helicase loader shows a notable structural similarity to the replication factor C clamp loader, suggesting a conserved mechanism of action

Deleción 14q proximal, presentación de dos casos y revisión de la literatura

Dismorfología, Citogenética y Clínica: Resultados de estudios sobre los datos del ECEMCHere we present two unrelated cases that came to our service for families that are looking for information on the diagnostic on malformation syndromes and infants with congenital defects. Both cases show as common signs psychomotor delay, microcephaly, corpus callosum agenesis and inespecific facial phenotype. We perform a high resolution G-bands karyotypes, and both of them showed a "de novo" deletion in the proximal region of a chromosome 14, with different break points but with a common region deleted. The karyotype of the first case was 46,XY, del(14)(q12;q21.1), and the karyotype of the second case 46,XX del(14)(q11.2;q13.1). We discussed the possible candidates genes that could be related with the phenotype and review the different reported cases.N

Monososomy 1p36: A clinically recognizable syndrome

Dismorfología, Citogenética y Clínica: Resultados sobre los datos del ECEMCPure 1p36 deletion is considered a new delineated syndrome that probably is a contiguous gene syndrome, presenting a pattern of clinical manifestation that may be recognizable. This includes moderate to severe psychomotor retardation, hypotonia, microcephaly, postnatal growth retardation, seizures and craniofacial dysmorphism (deep set eyes, low nasal bridge, large anterior fontanelle, midface hypoplasia) which should lead to perform a chromosomal study particularly focussed on this type of deletion. Terminal region 1p is difficult to visualize and its alterations will only be detected in a High Resolution G-band karyotype, followed by Fluorescence in situ Hybridization techniques (FISH). Here we present a case which was diagnosed as having a 1p36.22 deletion with High Resolution G-band karyotype confirmed by telomeric FISH.N

SITUACIONES DE LAS PRÁCTICAS CLÍNICAS QUE PROVOCAN ESTRÉS EN LOS ESTUDIANTES DE ENFERMERÍA

Observacional, cross-sectional comparative study given to the 3 courses students of infirmary registered in course 2004-05 in the School of Meixoeiro (Vigo), with the objective to valuate situations of the clinical practices, grouped by factors, are but more stressant for the students. The Kezkak and Stai questionnaires have been used to make. Participation in the study has been of the 85.30%. with a rank of ages between 19-41 years. The obtained average scores in our school reflect a high score in almost all the items considered like leading factors of stress, in comparison with the students of other studies. When making the correlation between anxiety characteristic, anxiety state and the situations , we have found significant between some of the factors and anxiety state, but not in anxiety characteristic, which seem to indicate that the stress situations that arelived with greater intensity are more related to the insecurity than with a characteristic of its character. As a measure to improve the level of anxiety of our students in the accomplishment of its clinical practices we propose interventions that facilitate the education of relaxation techniques and facing facts.Estudio observacional, transversal comparativo, realizado a los alumnos de los tres cursos de enfermería matriculados en el curso 2004-05 en la Escuela do Meixoeiro (Vigo), con el objetivo de valorar qué situaciones de las prácticas clínicas, agrupadas por factores, resultan más estresantes para los/las estudiantes. La medición se ha realizado con los cuestionarios Kezkak y Stai. La participación en el estudio ha sido del 85,30%, con un rango de edad entre 19-41 años. Las puntuaciones medias obtenidas en nuestra Escuela reflejan una puntuación alta en casi todos los ítems considerados como factores desencadenantes de estrés, en comparación con los alumnos de otros estudios. Al realizar la correlación entre ansiedad rasgo, ansiedad estado y las situaciones estresantes, hemos encontrado significación entre algunos de los factores y la ansiedad estado, pero no en la ansiedad rasgo, lo que parece indicar que las situaciones de estrés que viven con mayor intensidad están más relacionadas con la inseguridad que con un rasgo de su carácter. Como medida para mejorar el nivel de ansiedad de nuestros alumnos en la realización de sus prácticas clínicas proponemos intervenciones que faciliten la enseñanza de técnicas de relajación y afrontamiento