Pediatric thyroid cancer

Thyroid cancer is a rare disease in pediatric age; however it is increasing in the last few years, mainly in adolescent women. Although children and adult thyroid cancer are similar, they have some particular differences. The aim of this report is to analyze those differences, emphasizing the particularities of thyroid cáncer in pediatric age./nThe development of molecular genetic testing has allowed a deeper understanding of genetic predisposition síndromes, such as MEN2A, which has led to a significant increase in prophylactic thyroidectomies. The most frequent histological group is differentiated cáncer, specifically papilar type. At the time of diagnosis in children thyroid cancer presents a greater size and extensión, and more probabilities of multifocality and metastasis than in adults. The short-term prognosis is excellent; however in the long-term there are a significant number of recurrences and second tumors. It is important to carry out a personalized medicine, and to create diagnostic protocols. A Deep tumor characterization and the prognosis stratification will be essential to choose the correct treatment for each case, also to achieve maximum effectiveness, survival and to minimize side effects.Introducción y objetivo: El cáncer de tiroides es una enfermedad rara en la edad pediátrica que está aumentando en los últimos años, principalmente en mujeres adolescentes. Aunque guarda similitudes con el cáncer tiroideo del adulto tiene una serie de peculiaridades que lo diferencian. Nuestro objetivo es mostrar estas diferencias, resaltando las particularidades de esta enfermedad en la edad pediátrica frente a la del adulto./nLos avances en las técnicas diagnósticas de genética molecular han permitido nuevos descubrimientos acerca de la génesis de tumores tiroideos en edades tempranas. También han supuesto un incremento de los diagnósticos de síndromes de predisposición genética, principalmente MEN2A, que ha producido un aumento significativo de tiroidectomías profilácticas. Los tipos histológicos más frecuentes son los cánceres diferenciados, principalmente el papilar. Al diagnóstico en edad pediátrica, suelen presentar un mayor tamaño, extensión, y probabilidades de multifocalidad y metástasis que en el adulto. A corto plazo el pronóstico es excelente; sin embargo, a largo plazo existe un número importante de recaídas y de aparición de segundos tumores. Para su tratamiento y seguimiento son necesarias unidades de alta especialización pediátrica que incluyan cirujanos expertos en tiroides. Se debe tender a la medicina personalizada estableciendo protocolos diagnósticos que caractericen correctamente el tumor y estratifiquen el pronóstico, adaptando la cirugía, la administración de yodo-131 y los nuevos tratamientos farmacológicos para buscar la máxima efectividad y supervivencia y minimicen los efectos secundarios

Influencia de un programa de ejercicios físicos adaptados para el desarrollo de la coordinación motriz en niños de 8 a 12 años del equipo de atletismo Marlins de Ciudad del Carmen, México

ejercicios físicos adaptados ejerce sobre el desarrollo de la coordinación motriz en niños que entrenan atletismo del equipo Marlin´s, lo que permitirá a futuro ser parte de un grupo de atletas, que tengan un buen nivel competitivo en esta disciplina. La investigación es de tipo longitudinal, al realizarse las mediciones a lo largo del tiempo, se enmarca en un diseño pre experimental con pre-test y post-test al mismo grupo. Se hace una comparación de muestra pareadas para eliminar el sesgo de error que tiene el pre-experimento. Los métodos utilizados para dar respuesta a la problemática detectada son diversos con énfasis en la medición como método principal que permitió realizar un análisis estadístico acorde al tipo de estudio seleccionado. La contribución se materializa en la propia concepción del programa motriz a los niños que entrenan atletismo. Las conclusiones refieren que derivado del diagnóstico se observó en la muestra seleccionada dificultades en la coordinación motriz, lo que demostró la necesidad de la elaboración de este programa. Después de aplicado, pudo comprobarse que el mismo influyó positivamente en el proceso de entrenamiento del atletismo, se logró mejorar significativamente la coordinación motriz en niños de 8 a 12 años del equipo de atletismo Marlins y con ello la ejecución de las diferentes técnicas empleadas en este deporte. Palabras clave: Coordinación motriz, entrenamiento, atletismo.   ABSTRACT The purpose of the research was to determine the influence that an adapted physical exercise program exerts on the development of motor coordination in children who train athletics for the Marlin's team, which will allow them to be part of a group of athletes in the future, who have a good competitive level in this discipline. The research is of a longitudinal type, as the measurements are made over time, it is part of a pre-experimental design with pre-test and post-test to the same group. A comparison of paired samples is made to eliminate the error bias that the pre-experiment has. The methods used to respond to the detected problems are diverse with emphasis on measurement as the main method that allowed statistical analysis according to the type of study selected. The contribution is materialized in the very conception of the motor program for children who train athletics. The conclusions refer that derived from the diagnosis, difficulties in motor coordination were observed in the selected sample, which demonstrated the need for the development of this program. After applied, it could be verified that it had a positive influence on the athletics training process, it was possible to significantly improve motor coordination in children from 8 to 12 years of age from the Marlins athletics team and with it the execution of the different techniques used in this sport. Keywords: Motor coordination, training, athletics

Childhood B-Cell Preleukemia Mouse Modeling

Leukemia is the most usual childhood cancer, and B-cell acute lymphoblastic leukemia (B-ALL) is its most common presentation. It has been proposed that pediatric leukemogenesis occurs through a “multi-step” or “multi-hit” mechanism that includes both in utero and postnatal steps. Many childhood leukemia-initiating events, such as chromosomal translocations, originate in utero, and studies so far suggest that these “first-hits” occur at a far higher frequency than the incidence of childhood leukemia itself. The reason why only a small percentage of the children born with such preleukemic “hits” will develop full-blown leukemia is still a mystery. In order to better understand childhood leukemia, mouse modeling is essential, but only if the multistage process of leukemia can be recapitulated in the model. Therefore, mouse models naturally reproducing the “multi-step” process of childhood B-ALL will be essential to identify environmental or other factors that are directly linked to increased risk of disease.Research in CV-D group has been funded by Instituto de Salud Carlos III (ISCIII), through a “Miguel Servet Grant” (CPII19/00024-AES 2017–2020); co-funded by the European Union. Research in IS-G group is partially supported by FEDER and by SAF2015-64420-R MINECO/FEDER, UE, RTI2018-093314-B-I00 MCIU/AEI/FEDER, UE, by PID2021-122185OB-I00 MCIU/AEI/FEDER, UE, and by Junta de Castilla y León (UIC-017, CSI001U16, CSI234P18, and CSI144P20). IS-G have been supported by the Fundacion Unoentrecienmil (CUNINA project). CC and IS-G have been supported by the Fundación Científica de la Asociación Española contra el Cáncer (PRYCO211305SANC). Research at CC’s laboratory was partially supported by Ministerio de Ciencia e Innovación/AEI/FEDER (PID2021-122787OB-I00), FEDER MINECO (SAF2017-83061-R), the “Fundación Ramón Areces” and a Research Contract with the “Fundación Síndrome de Wolf-Hirschhorn o 4p-”. Institutional grants from the “Fundación Ramón Areces” and “Banco de Santander” to the CBMSO are also acknowledged. J.M.-C. is the recipient of a UAM FPU fellowship. AC-G (CSI067-18) and MI-H (CSI021-19) are supported by FSE-Conserjería de Educación de la Junta de Castilla y León 2019 and 2020 (ESF—European Social Fund) fellowship, respectively. SA-A is supported by an Ayuda para Contratos predoctorales para la formación de doctores (PRE2019-088887). L.S. is supported by a scholarship from University of Salamanca co-financed by Banco Santander and ESF

Thyroid nodules in children

Introduction and objective: Thyroid nodules in children are rare (2% of children have palpable thyroid nodules and 5% of children have thyroid nodules by ultrasonography)./nMost of these are benign and asymptomatic, but the percentage of nodules harboring cancer in children is higher than in adults: the rate of malignancy varies from 10 to 50% depending on published case series. For this reason, it is very important evaluating and monitoring the thyroid nodules in children./nSynthesis: The thyroid gland in children is more susceptible to certain carcinogenic agents than the thyroid gland in adults. Thus, clinical following of the thyroid nodules in children is very important./nThe American Thyroid Association (ATA) recognized that size criterion for performing fine-needle aspiration (FNA) in adults may not be appropriate in a growing thyroid gland in children. For this reason, the ATA recommended that ultrasound characterization and clinical context should be used in the evaluation./nBenign thyroid nodules must be monitored by periodic neck palpation and ultrasound examinations, so that if a significant increase in size is detected, it may lead to consider repeating FNA or performing a surgical excision./nConclusions: Clinical and ultrasonographic monitoring in thyroid nodule in children is very important due to its higher rate of malignancy than in adults.Introducción y objetivo: Los nódulos tiroideos son poco frecuentes en la infancia (2% de niños tienen nódulos palpables y un 5% de niños tienen nódulos detectados por ecografía). La mayoría son benignos y asintomáticos. Pero a diferencia de lo que sucede en el adulto, el riesgo de malignización de los mismos es mayor, de modo que, dependiendo de las series la tasa de malignidad se sitúa entre 10-50%. De ahí la importancia de hacer un seguimiento clínico adecuado./nSíntesis: La glándula tiroidea del niño es más sensible al efecto de determinados agentes carcinogénicos que la del adulto. Esto hace que el seguimiento de los nódulos tiroideos del niño que, en su mayoría son benignos y asintomáticos, cobre especial importancia./nLa American Thyroid Association (ATA) determinó que el criterio de tamaño utilizado en adultos para indicar punción aspiración con aguja fina (PAAF) podía no ser apropiado para la glándula del niño que está en crecimiento, por lo que recomendó también tener en cuenta las características ecográficas y el contexto clínico./nAnte los nódulos tiroideos benignos, se recomienda seguimiento clínico y ecográfico y ante aumentos de tamaño significativos, reconsiderar PAAF o cirugía./nConclusiones: Es importante hacer un seguimiento clínico y ecográfico en el nódulo tiroideo del niño por su mayor riesgo de malignización.Introduction and objective: Thyroid nodules in children are rare (2% of children have palpable thyroid nodules and 5% of children have thyroid nodules by ultrasonography)./nMost of these are benign and asymptomatic, but the percentage of nodules harboring cancer in children is higher than in adults: the rate of malignancy varies from 10 to 50% depending on published case series. For this reason, it is very important evaluating and monitoring the thyroid nodules in children./nSynthesis: The thyroid gland in children is more susceptible to certain carcinogenic agents than the thyroid gland in adults. Thus, clinical following of the thyroid nodules in children is very important./nThe American Thyroid Association (ATA) recognized that size criterion for performing fine-needle aspiration (FNA) in adults may not be appropriate in a growing thyroid gland in children. For this reason, the ATA recommended that ultrasound characterization and clinical context should be used in the evaluation./nBenign thyroid nodules must be monitored by periodic neck palpation and ultrasound examinations, so that if a significant increase in size is detected, it may lead to consider repeating FNA or performing a surgical excision./nConclusions: Clinical and ultrasonographic monitoring in thyroid nodule in children is very important due to its higher rate of malignancy than in adults.Introducción y objetivo: Los nódulos tiroideos son poco frecuentes en la infancia (2% de niños tienen nódulos palpables y un 5% de niños tienen nódulos detectados por ecografía). La mayoría son benignos y asintomáticos. Pero a diferencia de lo que sucede en el adulto, el riesgo de malignización de los mismos es mayor, de modo que, dependiendo de las series la tasa de malignidad se sitúa entre 10-50%. De ahí la importancia de hacer un seguimiento clínico adecuado./nSíntesis: La glándula tiroidea del niño es más sensible al efecto de determinados agentes carcinogénicos que la del adulto. Esto hace que el seguimiento de los nódulos tiroideos del niño que, en su mayoría son benignos y asintomáticos, cobre especial importancia./nLa American Thyroid Association (ATA) determinó que el criterio de tamaño utilizado en adultos para indicar punción aspiración con aguja fina (PAAF) podía no ser apropiado para la glándula del niño que está en crecimiento, por lo que recomendó también tener en cuenta las características ecográficas y el contexto clínico./nAnte los nódulos tiroideos benignos, se recomienda seguimiento clínico y ecográfico y ante aumentos de tamaño significativos, reconsiderar PAAF o cirugía./nConclusiones: Es importante hacer un seguimiento clínico y ecográfico en el nódulo tiroideo del niño por su mayor riesgo de malignización

The Second Oncogenic Hit Determines the Cell Fate of ETV6-RUNX1 Positive Leukemia

© 2021 Rodríguez-Hernández, Casado-García, Isidro-Hernández, Picard, Raboso-Gallego, Alemán-Arteaga, Orfao, Blanco, Riesco, Prieto-Matos, García Criado, García Cenador, Hock, Enver, Sanchez-Garcia and Vicente-Dueñas.ETV6-RUNX1 is almost exclusively associated with childhood B-cell acute lymphoblastic leukemia (B-ALL), but the consequences of ETV6-RUNX1 expression on cell lineage decisions during B-cell leukemogenesis are completely unknown. Clinically silent ETV6-RUNX1 preleukemic clones are frequently found in neonatal cord blood, but few carriers develop B-ALL as a result of secondary genetic alterations. The understanding of the mechanisms underlying the first transforming steps could greatly advance the development of non-toxic prophylactic interventions. Using genetic lineage tracing, we examined the capacity of ETV6-RUNX1 to instruct a malignant phenotype in the hematopoietic lineage by cell-specific Cre-mediated activation of ETV6-RUNX1 from the endogenous Etv6 gene locus. Here we show that, while ETV6-RUNX1 has the propensity to trigger both T- and B-lymphoid malignancies, it is the second hit that determines tumor cell identity. To instigate leukemia, both oncogenic hits must place early in the development of hematopoietic/precursor cells, not in already committed B-cells. Depending on the nature of the second hit, the resulting B-ALLs presented distinct entities that were clearly separable based on their gene expression profiles. Our findings give a novel mechanistic insight into the early steps of ETV6-RUNX1+ B-ALL development and might have major implications for the potential development of ETV6-RUNX1+ B-ALL prevention strategies.Research in CV-D group has been funded by Instituto de Salud Carlos III through the project “PI17/00167” and by a “Miguel Servet Grant” (CPII19/00024—AES 2017–2020), co-funded by European Regional Development Fund/European Social Fund (“A way to make Europe”/“Investing in your future”). Research in the IS-G group is partially supported by FEDER and SAF2015-64420-R MINECO/FEDER, UE, RTI2018-093314-B-I00 MCIU/AEI/FEDER, UE, and by Junta de Castilla y León (UIC-017, CSI001U16, CSI234P18, and CSI144P20). The IS-G lab is a member of the EuroSyStem and the DECIDE Network funded by the European Union under the FP7 program. CV-D and IS-G have been supported by the German Federal Office for Radiation Protection (BfS)–Germany (FKZ: 3618S32274). IS-G has been supported by the Fundacion Unoentrecienmil (CUNINA project). HH was supported by a Hyundai Hope on Wheels scholar grant. GR-H was supported by FSE-Conserjería de Educación de la Junta de Castilla y León (CSI001-15). AC-G and MI-H are supported by FSE-Conserjería de Educación de la Junta de Castilla y León 2019 and 2020 (ESF—European Social Fund) fellowship, respectively (REF. CSI067-18 and CSI021-19). JR-G was supported by a scholarship from the University of Salamanca, co-financed by Banco Santander and ESF. SA-A was supported by RTI2018-093314-B-I00 MCIU/AEI/FEDER fellowship (PRE2019-088887)

The Second Oncogenic Hit Determines the Cell Fate of ETV6-RUNX1 Positive Leukemia

ETV6-RUNX1 is almost exclusively associated with childhood B-cell acute lymphoblastic leukemia (B-ALL), but the consequences of ETV6-RUNX1 expression on cell lineage decisions during B-cell leukemogenesis are completely unknown. Clinically silent ETV6-RUNX1 preleukemic clones are frequently found in neonatal cord blood, but few carriers develop B-ALL as a result of secondary genetic alterations. The understanding of the mechanisms underlying the first transforming steps could greatly advance the development of non-toxic prophylactic interventions. Using genetic lineage tracing, we examined the capacity of ETV6-RUNX1 to instruct a malignant phenotype in the hematopoietic lineage by cell-specific Cre-mediated activation of ETV6-RUNX1 from the endogenous Etv6 gene locus. Here we show that, while ETV6-RUNX1 has the propensity to trigger both T- and B-lymphoid malignancies, it is the second hit that determines tumor cell identity. To instigate leukemia, both oncogenic hits must place early in the development of hematopoietic/precursor cells, not in already committed B-cells. Depending on the nature of the second hit, the resulting B-ALLs presented distinct entities that were clearly separable based on their gene expression profiles. Our findings give a novel mechanistic insight into the early steps of ETV6-RUNX1+ B-ALL development and might have major implications for the potential development of ETV6-RUNX1+ B-ALL prevention strategies

Transient inhibition of the JAK/STAT pathway prevents B-ALL development in genetically predisposed mice

Preventing development of childhood B-cell acute lymphoblastic leukemia (B-ALL), a disease with devastating effects, is a longstanding and unsolved challenge. Heterozygous germline alterations in the PAX5 gene can lead to B-ALL upon accumulation of secondary mutations affecting the JAK/STAT signaling pathway. Preclinical studies have shown that this malignant transformation occurs only under immune stress such as exposure to infectious pathogens. Here we show in Pax5+/− mice that transient, early-life administration of clinically relevant doses of ruxolitinib, a JAK1/2 inhibitor, significantly mitigates the risk of B-ALL following exposure to infection; 1 of 29 animals treated with ruxolitinib developed B-ALL versus 8 of 34 untreated mice. Ruxolitinib treatment preferentially targeted Pax5+/− versus wild-type B-cell progenitors and exerted unique effects on the Pax5+/− B-cell progenitor transcriptional program. These findings provide the first in vivo evidence for a potential strategy to prevent B-ALL development.C. Cobaleda and C. Vicente-Dueñas labs are members of the EU COST Action LEGEND (CA16223). Research in C. Vicente-Dueñas group has been funded by Instituto de Salud Carlos III through the project " PI17/00167 and by a “Miguel Servet Grant” [CPII19/00024 - AES 2017-2020; co-funded by European Regional Development Fund (ERDF)/European Social Fund (ESF) "A way to make Europe"/"Investing in your future"]. J.J. Yang and K.E. Nichols receive funding from the American Lebanese Syrian Associated Charities (ALSAC) and R01CA241452 from the NCI. Research in ISG group is partially supported by FEDER and by SAF2015-64420-R MINECO/FEDER, UE, RTI2018-093314-B-I00 MCIU/AEI/FEDER, UE, 9659122185-122185-4-21 MCIU/AEI/FEDER, UE, by Junta de Castilla y León (UIC-017, CSI001U16, CSI234P18, and CSI144P20). M. Ramírez-Orellana and I. Sánchez-García have been supported by the Fundacion Unoentrecienmil (CUNINA project). C. Cobaleda, M. Ramírez-Orellana, and I. Sánchez-García have been supported by the Fundación Científica de la Asociación Española contra el Cáncer (PRYCO211305SANC). A. Casado-García (CSI067-18) and M. Isidro-Hernández (CSI021-19) are supported by FSE-Conserjería de Educación de la Junta de Castilla y León 2019 and 2020 (ESF, European Social Fund) fellowship, respectively. J. Raboso-Gallego is supported by a scholarship from University of Salamanca co-financed by Banco Santander and ESF. S. Alemán-Arteaga is supported by an Ayuda para Contratos predoctorales para la formación de doctores (PRE2019-088887)

Deus

A relação entre a arte e a transcendência é imemorial. Uma sociedade interroga-se sobre a vida e a morte, desenvolve rituais e estabelece mediações através da oferta de objetos, de sacrifícios, de representações, de práticas funerárias, de comportamentos que não surgem da necessidade biológica, surgem da necessidade pensada, ou melhor, surgem do espírito. A questão estabelece-se entre o pensamento e as coisas. As coisas, o seu destino, o seu processo, o seu devir, têm regularidades, e irregularidades. Sobre as regularidades, como a quantidade, a permanência, a repetição, podemos estabelecer representações, ou relações de conhecimento. Sobre as irregularidades, percebidas como arbitrárias, que provocam incerteza, vida e morte, destinos indeterminados, podemos pensar uma determinação exterior, que nos transcende na duração e no conhecimento. Ao lançar “Deus” como tema deste número da revista Estúdio teve-se a perceção inteira da sua profundidade. A condição humana faz-se da representação da sua finitude, na mesma medida da grandeza do que a transcende. Assim foi, neste número, o tema do desafio lançado pela Estúdio. Adicionou-se este tema ao escopo que a revista Estúdio sempre tem apresentado, e que a distingue, ao solicitar aos artistas e criadores que apresentem as suas perspetivas sobre as obras de seus companheiros de profissão, colocando um ênfase no estudo de artistas que são menos conhecidos, e dando prioridade aos originários dos países abrangidos pelos idiomas da revista, português e espanhol. Este número 10 da Estúdio, dedicado ao tema Deus, é constituído por 19 artigos, selecionados a partir de 46 submissões, a que se adicionou um dossier editorial, perfazendo assim um total de 21 artigos e 1 entrevista.info:eu-repo/semantics/publishedVersio

Local hydrological conditions influence tree diversity and composition across the Amazon basin

Tree diversity and composition in Amazonia are known to be strongly determined by the water supplied by precipitation. Nevertheless, within the same climatic regime, water availability is modulated by local topography and soil characteristics (hereafter referred to as local hydrological conditions), varying from saturated and poorly drained to well-drained and potentially dry areas. While these conditions may be expected to influence species distribution, the impacts of local hydrological conditions on tree diversity and composition remain poorly understood at the whole Amazon basin scale. Using a dataset of 443 1-ha non-flooded forest plots distributed across the basin, we investigate how local hydrological conditions influence 1) tree alpha diversity, 2) the community-weighted wood density mean (CWM-wd) – a proxy for hydraulic resistance and 3) tree species composition. We find that the effect of local hydrological conditions on tree diversity depends on climate, being more evident in wetter forests, where diversity increases towards locations with well-drained soils. CWM-wd increased towards better drained soils in Southern and Western Amazonia. Tree species composition changed along local soil hydrological gradients in Central-Eastern, Western and Southern Amazonia, and those changes were correlated with changes in the mean wood density of plots. Our results suggest that local hydrological gradients filter species, influencing the diversity and composition of Amazonian forests. Overall, this study shows that the effect of local hydrological conditions is pervasive, extending over wide Amazonian regions, and reinforces the importance of accounting for local topography and hydrology to better understand the likely response and resilience of forests to increased frequency of extreme climate events and rising temperatures

Estimating the global conservation status of more than 15,000 Amazonian tree species

Estimates of extinction risk for Amazonian plant and animal species are rare and not often incorporated into land-use policy and conservation planning. We overlay spatial distribution models with historical and projected deforestation to show that at least 36% and up to 57% of all Amazonian tree species are likely to qualify as globally threatened under International Union for Conservation of Nature (IUCN) Red List criteria. If confirmed, these results would increase the number of threatened plant species on Earth by 22%. We show that the trends observed in Amazonia apply to trees throughout the tropics, and we predict thatmost of the world’s >40,000 tropical tree species now qualify as globally threatened. A gap analysis suggests that existing Amazonian protected areas and indigenous territories will protect viable populations of most threatened species if these areas suffer no further degradation, highlighting the key roles that protected areas, indigenous peoples, and improved governance can play in preventing large-scale extinctions in the tropics in this century