Nou avenç en teràpia gènica

Un grup d'investigadors del CBATEG de la UAB, dirigit pel doctor Miguel Chillón, ha descrit el desenvolupament d'un sistema nou de producció d'adenovirus d'última generació (utilitzats com a vectors per a tractaments de teràpia gènica) que permet reduir, significativament, els inconvenients que existeixen fins ara per realitzar assaigs en humans. La UAB ha patentat recentment aquesta tècnica.Un grupo de investigadores del CBATEG de la UAB, dirigido por el doctor Miguel Chillón, ha descrito el desarrollo de un nuevo sistema de producción de adenovirus de última generación (utilizados como vectores para tratamientos de terapia génica) que permite reducir significativamente los inconvenientes existentes hasta ahora para realizar ensayos en humanos. La UAB ha patentado recientemente esta técnica.A group of CTABEG researchers, directed by Dr Miguel Chillon, describe the development of a new method for producing last-generation adenoviruses (used as vectors in gene therapy) which significantly reduce the inconveniences that existed until now in clinical trials carried out with humans. This method has been recently patented by the UAB

AAV-mediated expression of secreted and transmembrane αKlotho isoforms rescues relevant aging hallmarks in senescent SAMP8 mice

Senescence represents a stage in life associated with elevated incidence of morbidity and increased risk of mortality due to the accumulation of molecular alterations and tissue dysfunction, promoting a decrease in the organism's protective systems. Thus, aging presents molecular and biological hallmarks, which include chronic inflammation, epigenetic alterations, neuronal dysfunction, and worsening of physical status. In this context, we explored the AAV9-mediated expression of the two main isoforms of the aging-protective factor Klotho (KL) as a strategy to prevent these general age-related features using the senescence-accelerated mouse prone 8 (SAMP8) model. Both secreted and transmembrane KL isoforms improved cognitive performance, physical state parameters, and different molecular variables associated with aging. Epigenetic landscape was recovered for the analyzed global markers DNA methylation (5-mC), hydroxymethylation (5-hmC), and restoration occurred in the acetylation levels of H3 and H4. Gene expression of pro- and anti-inflammatory mediators in central nervous system such as TNF-α and IL-10, respectively, had improved levels, which were comparable to the senescence-accelerated-mouse resistant 1 (SAMR1) healthy control. Additionally, this improvement in neuroinflammation was supported by changes in the histological markers Iba1, GFAP, and SA β-gal. Furthermore, bone tissue structural variables, especially altered during senescence, recovered in SAMP8 mice to SAMR1 control values after treatment with both KL isoforms. This work presents evidence of the beneficial pleiotropic role of Klotho as an anti-aging therapy as well as new specific functions of the KL isoforms for the epigenetic regulation and aged bone structure alteration in an aging mouse model. Intraventricular administration of AAV vectors expressing secreted and transmembrane Klotho isoforms, rescued accelerated aging phenotype of SAMP8 mice. An improvement in cognitive and physical performance, recovery of epigenetic, inflammatory and senescence markers, as well as structural changes in long bones of these mice was detected

Zinc-Assisted Microscale Granules Made of the SARS-CoV-2 Spike Protein Trigger Neutralizing, Antivirus Antibody Responses

Altres ajuts: acords transformatius de la UABThe development of new and more efficient vaccination approaches is a constant need, due to the pressure of historical and emerging infectious diseases and the limited efficacy and universality of the current vaccination technologies. Peptides and recombinant proteins have been explored for decades as subunit vaccines for bacterial and viral infections, presented either as soluble protein species or as virus-like assemblies. Recently, synthetic secretory protein-only microscale granules have been developed as dynamic depots for sustained protein release. They are based on the reversible coordination between ionic Zn and histidine residues, which promotes a fast formation of granular particles in vitro out of soluble protein and a slow release of such building block protein in vivo through the physiological chelation of the metal. Such an endocrine-like platform represents a new drug delivery system fully validated in oncology by which soluble and functional protein drugs are progressively released from the granules and made available for antitumor activities upon subcutaneous administration. By exploring such an approach for immunization here, microparticles made of a recombinant form of the receptor binding domain (RBD) of SARS-CoV-2 were tested as an antigen delivery system for induction of antibody responses against the virus upon administration of the material in the absence of added adjuvants. Also, the comparison between protein materials produced in bacterial, mammalian, or insect cell factories has demonstrated a moderate impact of protein glycosylation on the final immunological performance of the system. Therefore, we propose the consideration of synthetic protein secretory granules as a new sustainable immunization platform based on fully manageable, self-organized, and self-formulated immunogens, aimed at reducing the dosage, costs, and complexity of vaccination regimens

Motivos de abandono y no práctica de actividad físicodeportiva

A pesar de los reconocidos beneficios físicos, psíquicos y socialesque la práctica de actividad físico-deportiva produce en la salud de los jóvenes,la prevalencia de abandono y falta de este tipo de actividades está mostrandoun importante aumento a nivel mundial, particularmente en los países desarrollados.Se precisan actuaciones educativas inmediatas para frenar estasituación. El objetivo del estudio es analizar la expresión de interés hacia laactividad físico-deportiva atendiendo al nivel de participación de ésta, y conocerlos motivos de abandono y no práctica en una muestra representativade adolescentes españoles. Se efectuó un estudio descriptivo de corte transversaly se empleó la encuesta sobre comportamientos, actitudes y valores sobreactividad físico-deportiva del estudio AVENA (Alimentación y Valoracióndel Estado Nutricional en Adolescentes). La muestra fue de 2.859 adolescentesespañoles (1.357 hombres, 1.502 mujeres; rango de edad: 13-18,5 años)y elegida de entre los escolares de Enseñanza Secundaria, procedentes tantode centros públicos como privados de cinco ciudades españolas: Granada,Madrid, Murcia, Santander y Zaragoza. Los principales resultados verificanuna elevada expresión de interés hacia la práctica físico-deportiva aunque casila mitad de los adolescentes indican un nivel de participación insuficienterespecto a lo que realmente querrían practicar. La exigencia del estudio y lapereza y desgana suponen los principales motivos de abandono de la misma.Respecto a los motivos de no práctica, la falta de tiempo, seguido muy de lejospor la pereza, la falta de gusto hacia la misma y el cansancio por el estudio otrabajo. El género y la edad modifican significativamente la expresión de interésy los motivos de abandono y no práctica físico-deportiva. El conocimientode estos motivos podría permitir desarrollar programas de intervención eficacesy duraderos en la adopción de estilos de vida saludables en los jóvenes

Attitudes toward the physical activity and sport practice in Spanish adolescents: the AVENA study

El objetivo del estudio se centra en conocer las actitudes hacia la práctica de actividad físico deportiva orientada a la salud en una muestra representativa de adolescentes españoles. Para ello, se ha efectuado un estudio descriptivo de corte transversal, empleando la encuesta sobre comportamientos, actitudes y valores sobre actividad física y deportiva del Grupo AVENA. El análisis descriptivo e inferencial, nos permite obtener la opinión de 2.859 estudiantes, procedentes tanto de centros públicos como privados de cinco ciudades españolas: Granada, Madrid, Murcia, Santander y Zaragoza. Los principales resultados verifican que tanto chicos como chicas presentan una mayor orientación hacia actitudes relacionadas con el proceso (AP) de la actividad físico-deportiva que hacia actitudes referidas al resultado (AR) de dicha práctica. En ambos sexos, se produce una disminución progresiva en dicha orientación, tanto en las AP como en las AR, conforme aumenta la edad. En aquellos adolescentes que practican actividad física, la orientación hacia las actitudes es mayor que en adolescentes no practicantes. Como conclusión, las AP adquieren mayor importancia que las AR en los jóvenes adolescentes, siendo ambas mayores en chicos respecto a chicas y disminuyendo los valores de ambas conforme aumenta la edad. El conocimiento facilitado en este trabajo podría servir de apoyo para perfeccionar las diversas estrategias de promoción de la salud sobre las que asentar la adquisición de nuevos estilos de vida entre la población joven de una forma estable y duradera.The aim of this study was to know the attitudes toward the physical activity and sport practice oriented to health in a representative sample of Spanish adolescents. A descriptive cross-sectional study was implemented and the survey about behaviours, attitudes and values related to physical activity and sport practice developed in the AVENA study was used. The sample size was 2859 Spanish students from public and private secondary schools in 5 Spanish cities: Granada, Madrid, Murcia, Santander and Zaragoza. The main results verify that both boys and girls have a greater orientation towards process-related attitudes (PA) of physical activity and sport that outcome-related attitudes (AR) of the practice. In boys and girls, both AP and AR both genders, there is a progressive decrease when increasing the age. Adolescents who engaged in physical activity had higher levels of attitudes than non-practitioners. In conclusion, AP became more important than AR in young adolescents; both AP and AR were higher in boys than in girls and attitude values decreased with increasing age. The knowledge of attitudes might allow to develop effective and long-term successful intervention programmes for adopting healthy lifestyles in the current young peopl

Genetic complexity impacts the clinical outcome of follicular lymphoma patients

© The Author(s) 2021.Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma (NHL, 20–30%) after diffuse large B-cell lymphoma (DLBCL). Despite the introduction of rituximab and the high response rate to first-line treatment, approximately 20% of the FL patients relapse or progress within 2 years of receiving first-line therapy. Therefore, the major challenge is finding biomarkers that identify high-risk patients at diagnosis.This work was partially supported by the Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness PI15/01393, PI18/00410, CIBERONC-CB16/12/00233, and “Una manera de hacer Europa” (Innocampus; CEI-2010-1-0010)”, the Education Council or Health Council of the Junta de Castilla y León (CAS102P17, GRS 1180/A/15), Spanish Association Against Cancer (AECC; PROYE18020BEA), and Gilead Sciences (GLD17/00334). CJ, MES, and AMe are supported by the ISCII (CD19/00030, CPII18/00028, and FI19/00320). MGA, IPC, and CJ were supported by the Spanish Society of Hematology Foundation (FEHH). All Spanish funding is co-sponsored by the European Union FEDER program

Motivos de práctica de actividad física-deportiva en adolescentes españoles: Estudio Avena

Fundamentos: La práctica de actividad físico-deportiva es un medio ideal para la obtención de beneficios bio-psico-sociales en la salud de los jóvenes. El objetivo del estudio fue conocer los motivos de práctica de actividad físico-deportiva en una muestra representativa de adolescentes españoles. Métodos: Se efectuó un estudio descriptivo de corte transversal y se empleó la encuesta sobre comportamientos, actitudes y valores sobre actividad física y deportiva del Grupo AVENA. La muestra fueron 2.859 estudiantes, procedentes de centros públicos y privados de cinco ciudades españolas: Granada, Madrid, Murcia, Santander y Zaragoza. Resultados: La diversión, la realización de ejercicio físico, estar con los amigos y el gusto hacia la práctica son, en ese orden, los principales motivos señalados para realizar actividad físico-deportiva en el tiempo libre. El género y la edad modifican significativamente los motivos de práctica físicodeportiva

Motives of Doprout and Non Practice Physical Activity and Sport in Spanish Adolescents: The Avena Study

A pesar de los reconocidos beneficios físicos, psíquicos y sociales que la práctica de actividad físico-deportiva produce en la salud de los jóvenes, la prevalencia de abandono y falta de este tipo de actividades está mostrando un importante aumento a nivel mundial, particularmente en los países desarrollados. Se precisan actuaciones educativas inmediatas para frenar esta situación. El objetivo del estudio es analizar la expresión de interés hacia la actividad físico-deportiva atendiendo al nivel de participación de ésta, y conocer los motivos de abandono y no práctica en una muestra representativa de adolescentes españoles. Se efectuó un estudio descriptivo de corte transversal y se empleó la encuesta sobre comportamientos, actitudes y valores sobre actividad físico-deportiva del estudio AVENA (Alimentación y Valoración del Estado Nutricional en Adolescentes). La muestra fue de 2.859 adolescentes españoles (1.357 hombres, 1.502 mujeres; rango de edad: 13-18,5 años) y elegida de entre los escolares de Enseñanza Secundaria, procedentes tanto de centros públicos como privados de cinco ciudades españolas: Granada, Madrid, Murcia, Santander y Zaragoza. Los principales resultados verifican una elevada expresión de interés hacia la práctica físico-deportiva aunque casi la mitad de los adolescentes indican un nivel de participación insuficiente respecto a lo que realmente querrían practicar. La exigencia del estudio y la pereza y desgana suponen los principales motivos de abandono de la misma. Respecto a los motivos de no práctica, la falta de tiempo, seguido muy de lejos por la pereza, la falta de gusto hacia la misma y el cansancio por el estudio o trabajo. El género y la edad modifican significativamente la expresión de interés y los motivos de abandono y no práctica físico-deportiva. El conocimiento de estos motivos podría permitir desarrollar programas de intervención eficaces y duraderos en la adopción de estilos de vida saludables en los jóvenes.Despite the recognized physical, psychological and social benefits of physical and sport practice in the health of young people, prevalence of doprout and lack of such activities is increasing in developed countries. Interventions of different society institutions are required, being particularly relevant educational institutions. The aim of the study is to analyze the interest physical activity and sport regarding the level of participation in this practice and to know the reasons for abandoning and non practicing in a representative sample of Spanish adolescents. A descriptive cross-sectional study was implemented and the survey about behaviours, attitudes and values related to physical activity and sport practice, which was developed in the AVENA (Feeding and assessment of nutritional status of spanish adolescents) study. The sample size was 2859 Spanish adolescents (1.357 men, 1.502 women; age range: 13-18.5 years) and chosen from among students of secondary education, both from public and private schools in five Spanish cities: Granada, Madrid, Murcia, Santander and Zaragoza. The main results show a high level of interest about physical activity and sport practice although almost half of the adolescents show an insufficient level regarding the level that they would like to practice. The demanding school and laziness and reluctante are the main reasons for stop practicing. The reasons for no practicing are lack of time, and much further the laziness, lack of pleasure with the practice and tiredness because of the school or work. Gender and age modify significantly the interest and reasons for abandoning and non practicing physical activity and sports. The knowledge of these reasons could allow to develop effective and long-term successful intervention programmes for adopting healthy lifestyles in young people

Motives of practice physical activity and sport in Spanish adolescents: the AVENA study

Fundamentos: La práctica de actividad físico-deportiva es un medio ideal para la obtención de beneficios bio-psico-sociales en la salud de los jóvenes. El objetivo del estudio fue conocer los motivos de práctica de actividad físico-deportiva en una muestra representativa de adolescentes españoles. Métodos: Se efectuó un estudio descriptivo de corte transversal y se empleó la encuesta sobre comportamientos, actitudes y valores sobre actividad física y deportiva del Grupo AVENA. La muestra fueron 2.859 estudiantes, procedentes de centros públicos y privados de cinco ciudades españolas: Granada, Madrid, Murcia, Santander y Zaragoza. Resultados: La diversión, la realización de ejercicio físico, estar con los amigos y el gusto hacia la práctica son, en ese orden, los principales motivos señalados para realizar actividad físico-deportiva en el tiempo libre. El género y la edad modifican significativamente los motivos de práctica físicodeportiva. Conclusiones: El conocimiento de los motivos de práctica podría permitir desarrollar programas de intervención eficaces y duraderos en la adopción de estilos de vida saludables en los jóvenes actuales.Background: Practice of physical activity and sport is an ideal medium for obtain benefits biopsycho-socials health of young people. The aim of the current study is to know the reasons for practicing physical activity and sport in a representative sample of Spanish adolescents. Methods: A descriptive cross-sectional study was implemented and the survey about behaviours, attitudes and values related to physical activity and sport practice, which was developed in the AVENA study was used. The sample size was 2859 Spanish students from public and private secondary schools in 5 Spanish cities: Granada, Madrid, Murcia, Santander and Zaragoza. Results: The amusement, doing exercise, being with friends and the pleasure of this practice are, in this order, the main reasons for practicing physical activity and sport in their free time. Gender and age modify significantly the reasons for practicing physical activity and sports. Conclusions: The knowledge of the reason of practicing could allow to develop effective and longterm successful intervention programmes for adopting healthy lifestyles in the currently young people.Grupo FORCE (HUM-386). Departamento de Didáctica y Organización escolar de la Universidad de Granada

Characteristics and outcomes of adult patients in the PETHEMA registry with relapsed or refractory FLT3-ITD mutation-positive acute myeloid leukemia

This retrospective study investigated outcomes of 404 patients with relapsed/refractory (R/R) FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) acute myeloid leukemia (AML) enrolled in the PETHEMA registry, pre-approval of tyrosine kinase inhibitors. Most patients (63%) had received first-line intensive therapy with 3 + 7. Subsequently, patients received salvage with intensive therapy (n = 261), non-intensive therapy (n = 63) or supportive care only (n = 80). Active salvage therapy (i.e., intensive or non-intensive therapy) resulted in a complete remission (CR) or CR without hematological recovery (CRi) rate of 42%. More patients achieved a CR/CRi with intensive (48%) compared with non-intensive (19%) salvage therapy (p < 0.001). In the overall population, median overall survival (OS) was 5.5 months; 1- and 5-year OS rates were 25% and 7%. OS was significantly (p < 0.001) prolonged with intensive or non-intensive salvage therapy compared with supportive therapy, and in those achieving CR/CRi versus no responders. Of 280 evaluable patients, 61 (22%) had an allogeneic stem-cell transplant after they had achieved CR/CRi. In conclusion, in this large cohort study, salvage treatment approaches for patients with FLT3-ITD mutated R/R AML were heterogeneous. Median OS was poor with both non-intensive and intensive salvage therapy, with best long-term outcomes obtained in patients who achieved CR/CRi and subsequently underwent allogeneic stem-cell transplant.This study was supported by Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Valencia, Spain [CB16/12/00284]