Cancer Predisposition Genes in Adolescents and Young Adults (AYAs): a Review Paper from the Italian AYA Working Group

Purpose of Review: The present narrative systematic review summarizes current knowledge on germline gene mutations predisposing to solid tumors in adolescents and young adults (AYAs). Recent Findings: AYAs with cancer represent a particular group of patients with specific challenging characteristics and yet unmet needs. A significant percentage of AYA patients carry pathogenic or likely pathogenic variants (PV/LPVs) in cancer predisposition genes. Nevertheless, knowledge on spectrum, frequency, and clinical implications of germline variants in AYAs with solid tumors is limited. Summary: The identification of PV/LPV in AYA is especially critical given the need for appropriate communicative strategies, risk of second primary cancers, need for personalized long-term surveillance, potential reproductive implications, and cascade testing of at-risk family members. Moreover, these gene alterations may potentially provide novel biomarkers and therapeutic targets that are lacking in AYA patients. Among young adults with early-onset phenotypes of malignancies typically presenting at later ages, the increased prevalence of germline PV/LPVs supports a role for genetic counseling and testing irrespective of tumor type

Exploiting pre-rRNA processing in Diamond Blackfan anemia gene discovery and diagnosis

Diamond Blackfan anemia (DBA), a syndrome primarily characterized by anemia and physical abnormalities, is one among a group of related inherited bone marrow failure syndromes (IBMFS) which share overlapping clinical features. Heterozygous mutations or single-copy deletions have been identified in 12 ribosomal protein genes in approximately 60% of DBA cases, with the genetic etiology unexplained in most remaining patients. Unlike many IBMFS, for which functional screening assays complement clinical and genetic findings, suspected DBA in the absence of typical alterations of the known genes must frequently be diagnosed after exclusion of other IBMFS. We report here a novel deletion in a child that presented such a diagnostic challenge and prompted development of a novel functional assay that can assist in the diagnosis of a significant fraction of patients with DBA. The ribosomal proteins affected in DBA are required for pre-rRNA processing, a process which can be interrogated to monitor steps in the maturation of 40S and 60S ribosomal subunits. In contrast to prior methods used to assess pre-rRNA processing, the assay reported here, based on capillary electrophoresis measurement of the maturation of rRNA in pre-60S ribosomal subunits, would be readily amenable to use in diagnostic laboratories. In addition to utility as a diagnostic tool, we applied this technique to gene discovery in DBA, resulting in the identification of RPL31 as a novel DBA gene. Am. J. Hematol. 89:985-991, 2014. (c) 2014 Wiley Periodicals, Inc

Los métodos didáctico musicales y la atención en relación al movimiento

La línea que dirige la orientación y el propósito de ésta investigación, se centra en realizar de forma panorámica, una visión en la que poner de relieve el grado de implementación de la atención en los distintos métodos didáctico musicales más relacionados con la docencia musical general, desde las propuestas taxonómicas diseñadas por el iniciador Émile Jacques-Dalcroze, pasando por diferentes proposiciones metodológicas, hasta los planteamientos considerados en el reciente método BAPNE. Para ello se tendrán en cuenta las diferentes aportaciones, clasificaciones de las mismas, priorizando aquellas con mayor grado de vinculación hacia los elementos del lenguaje musical más relacionados con el binomio movimiento y atención. De igual forma, se pone de relieve el diferente grado de tratamiento, sistematización y pertinente consideración de la atención con respecto a los diferentes métodos seleccionados en general y del movimiento en ellos de forma particular. El Método BAPNE, propone fundamentada y sistematizadamente, una serie de criterios por los que sus taxonomías optimizan las potencialidades didácticas del binomio movimiento-atención en el diseño de aplicaciones para el aula

La percusión corporal como estímulo para alumnos con déficit de atención y concentración

El objetivo de este estudio es desarrollar un protocolo de actividades a través del Método BAPNE con alumnos con dificultades de aprendizaje para la estimulación de la atención, concentración y memoria. Con ello queremos demostrar los beneficios que posee la percusión corporal a través de esta metodología y su relación con la creatividad y aprendizaje por proyectos. Con actividades muy específicas elaboradas por un grupo de investigación organizado por neurólogos y docentes ofrecemos nuevas vías de innovación docente para aplicar a diferentes colectivos educativos. El estudio se articula bajo unos objetivos centrados en la mejora de la capacidad de abstracción, percepción, atención, observación, concentración y aprendizaje. De forma paralela realizamos especial énfasis en la estimulación de la memoria sensorial (a través de los sentidos), memoria a corto plazo (inmediata y de trabajo) y en la memoria a largo plazo (episódica, semántica y procedimental). La batería de actividades sugeridas se combina para trabajar asociaciones, secuencias, actividades sensomotrices, repeticiones y descripciones corporales, combinaciones motoras a nivel biomecánico, capacidad de atención y de observación, lenguaje, relajaciones, visualizaciones y percepciones espacio-temporales. Así, sugerimos un modo de trabajo lo más holístico posible para ayudar a personas con problemas de atención y memoria

Pentraxin 3 plasma levels at graft-versus-host disease onset predict disease severity and response to therapy in children given haematopoietic stem cell transplantation

Acute Graft-versus-Host Disease (GvHD) remains a major complication of allogeneic haematopoietic stem cell transplantation, with a significant proportion of patients failing to respond to first-line systemic corticosteroids. Reliable biomarkers predicting disease severity and response to treatment are warranted to improve its management. Thus, we sought to determine whether pentraxin 3 (PTX3), an acutephase protein produced locally at the site of inflammation, could represent a novel acute GvHD biomarker. Using a murine model of the disease, we found increased PTX3 plasma levels after irradiation and at GvHD onset. Similarly, plasma PTX3 was enhanced in 115 pediatric patients on day of transplantation, likely due to conditioning, and at GvHD onset in patients experiencing clinical symptoms of the disease. PTX3 was also found increased in skin and colon biopsies from patients with active disease. Furthermore, PTX3 plasma levels at GvHD onset were predictive of disease outcome since they resulted significantly higher in both severe and therapyunresponsive patients. Multiple injections of rhPTX3 in the murine model of GvHD did not influence the disease course. Taken together, our results indicate that PTX3 constitutes a biomarker of GvHD severity and therapy response useful to tailor treatment intensity according to early risk-stratification of GvHD patients

Cancer burden in adolescents and young adults in Europe

Background Cancer epidemiology is unique in adolescents and young adults (AYAs; aged 15-39 years). The European Society for Medical Oncology/European Society for Paediatric Oncology (ESMO/SIOPE) AYA Working Group aims to describe the burden of cancers in AYAs in Europe and across European Union (EU) countries. Patients and methods We used data available on the Global Cancer Observatory. We retrieved crude and age-standardised (World Standard Population) incidence and mortality rates. We reported about AYA cancer burden in Europe and between 28 EU member states. We described incidence and mortality for all cancers and for the 13 cancers most relevant to the AYA population. Results Incidence and mortality varied widely between countries with the highest mortality observed in Eastern EU countries. Cancers of the female breast, thyroid and male testis were the most common cancers across countries followed by melanoma of skin and cancers of the cervix. Variations in cancer incidence rates across different populations may reflect different distribution of risk factors, variations in the implementation or uptake of screening as well as overdiagnosis. AYA cancer mortality disparities may be due to variation in early-stage diagnoses, different public education and awareness of cancer symptoms, different degrees of access or availability of treatment. Conclusions Our results highlight the future health care needs and requirements for AYA-specialised services to ensure a homogeneous treatment across different countries as well as the urgency for preventive initiatives that can mitigate the increasing burden