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Altres ajuts: PERIS (SLT017/20/000090), Ample evidence exists connecting dNTP pool dysregulation to cancer and genomic instability. SAMHD1, the unique dNTP triphosphohydrolase described in humans, has been proposed to play a key role in hematological cancers, although its value in advanced solid tumors has not yet been explored. Moreover, it has been proposed that SAMHD1 might fulfill the requirements of a driver gene in tumor development or might promote a so-called mutator phenotype. Here, we show that low SAMHD1 expression tumors show better prognosis in breast, ovarian, and lung advanced cancer. Moreover, low SAMHD1 expression is a positive predictive factor in lung and ovarian cancer treated with platin derivates and/or antimetabolites. In vitro evaluation of its underlying mechanism revealed that SAMHD1 KO cells presented enhanced susceptibility to DNA damage and subsequent induction of apoptosis of tumor cells. Our results provide strong evidence of the clinical importance of SAMHD1, becoming an interesting target for the development of personalized cancer treatments. SAMHD1 is a deoxynucleotide triphosphate (dNTP) triphosphohydrolase with important roles in the control of cell proliferation and apoptosis, either through the regulation of intracellular dNTPs levels or the modulation of the DNA damage response. However, SAMHD1's role in cancer evolution is still unknown. We performed the first in-depth study of SAMHD1's role in advanced solid tumors, by analyzing samples of 128 patients treated with chemotherapy agents based on platinum derivatives and/or antimetabolites, developing novel in vitro knock-out models to explore the mechanisms driving SAMHD1 function in cancer. Low (or no) expression of SAMHD1 was associated with a positive prognosis in breast, ovarian, and non-small cell lung cancer (NSCLC) cancer patients. A predictive value was associated with low-SAMHD1 expression in NSCLC and ovarian patients treated with antimetabolites in combination with platinum derivatives. In vitro, SAMHD1 kn

Thirty-six months is a key time to assess executive functions in premature children. Following an observational, cross sectional-comparative design, 57 children were assessed using development tests, parent reporting, and behavioural observation. The scores are in the average range, although greater vulnerability is observed in the motor skills, and in specific executive functions. The risk factors due to prematurity, sex, and behaviour observed during the assessment are related to achievement. The girls achieve better performance in global and fine motor skills. Lower gestational age is associated with poorer motor skills, and lower weight with linguistics. Parents of those born at higher birth weights or with lower prematurity report less Flexibility and Emotional Control. Data derived from functioning social observation support the results obtained using the development test and from the information provided by the parents. The results support a multi-method assessment at an early age be made part of protocol to reduce the impact of prematurity.

Validated physical activity (PA) questionnaires are crucial for collecting information in large epidemiological studies during childhood. Thus, this study analyzed the validity of a parent-reported PA questionnaire based on the Children’s Leisure Activities Study Survey by accelerometry in European children aged from 6 to 12 years old. We used data from 230 children of the Human Early-Life Exposome and Infancia y Medio Ambiente projects. Mean differences between moderate-to-vigorous PA (MVPA) reported by the questionnaire and the accelerometer were calculated (min/day), and its associated factors were explored by multiple robust linear regression. The agreement between methods was examined using a Bland–Altman plot. The concurrent validity of assessing MVPA was analyzed by cohort-adjusted Spearman’s partial correlations. ROC curve analysis was also used to explore the questionnaire’s capability to identify active children based on the World Health Organization guidelines. A moderate correlation was found between parent-reported and accelerometer MVPA (rho = 0.41, p < 0.001). The child’s sex (girl) was statistically associated with the mean MVPA difference between methods. However, this questionnaire accurately identified physically active children (area under the curve = 83.8% and 82.7% for boys and girls, cut-points = 68.6 and 45.4 min/day in MVPA, respectively). Consequently, this questionnaire is suitable for classifying active children in order to monitor public health interventions regarding PA.

Background: In the last decades, the birth of premature babies has increased, it is important to know the impact of certain variables, especially in the most vulnerable groups. Purpose: To analyse the relationship of gestational age (GA), weight and sex of the children, as well as the educa- tional level and age of the parents with the cognitive, motor and language development of a group of very pre- term births, assessed at 36 months. Design and methods: The research followed a descriptive, observational and cross-sectional design. Children's de- velopment was measured using the Bayley-III Scale. Descriptive analysis, bivariate and linear regression models were carried out. Results: Although the cognitive, motor and language development is within average levels, worse results are ev- idenced in the group of extreme premature, as opposed to the very premature. Boys score lower than girls, with these differences being more pronounced in the motor area. It also shows how the education level of both parents is related to the levels of development at 3 years of age of children born very prematurely, especially in language. Conclusions: Lower GA, male sex and lower parental educational level are associated with higher risk of develop- mental difficulties. Practice implications: The findings of this study are relevant to clinical practice because they suggest to develop protocols of evaluation and the follow up of all premature children beyond 36 months, as well as developing spe- cific intervention programmes for the most vulnerable of the premature groups

En el contexto de competencia presente en la sociedad de consumo actual, las marcas buscan acercarse cada vez más al cliente. Para conseguir este objetivo un punto clave es la ubicación de sus tiendas físicas, por lo que las compañías que quieren alcanzar un posicionamiento destacado en el mercado, deben elegir cuidadosamente dónde estar presentes, no sólo en términos de localización, sino también del edificio en el que se instalan. Y es que éstos no están elegidos al azar: se buscan construcciones singulares o con historia que permitan hacer de la marca un hito en la ciudad. En este trabajo se exponen varios ejemplos de esta dinámica en una misma marca, para ilustrar cómo un mismo edificio puede albergar usos diametralmente diferentes y la importancia que este hecho tiene para la imagen que se proyecta hacia los consumidores.

Validated physical activity (PA) questionnaires are crucial for collecting information in large epidemiological studies during childhood. Thus, this study analyzed the validity of a parent-reported PA questionnaire based on the Children’s Leisure Activities Study Survey by accelerometry in European children aged from 6 to 12 years old. We used data from 230 children of the Human Early-Life Exposome and Infancia y Medio Ambiente projects. Mean differences between moderate-to-vigorous PA (MVPA) reported by the questionnaire and the accelerometer were calculated (min/day), and its associated factors were explored by multiple robust linear regression. The agreement between methods was examined using a Bland–Altman plot. The concurrent validity of assessing MVPA was analyzed by cohort-adjusted Spearman’s partial correlations. ROC curve analysis was also used to explore the questionnaire’s capability to identify active children based on the World Health Organization guidelines. A moderate correlation was found between parent-reported and accelerometer MVPA (rho = 0.41, p < 0.001). The child’s sex (girl) was statistically associated with the mean MVPA difference between methods. However, this questionnaire accurately identified physically active children (area under the curve = 83.8% and 82.7% for boys and girls, cut-points = 68.6 and 45.4 min/day in MVPA, respectively). Consequently, this questionnaire is suitable for classifying active children in order to monitor public health interventions regarding PA.

The emerging SARS-CoV-2 variants of concern (VOCs) may display enhanced transmissibility, more severity and/or immune evasion; however, the pathogenesis of these new VOCs in experimental SARS-CoV-2 models or the potential infection of other animal species is not completely understood. Here we infected K18-hACE2 transgenic mice with B.1, B.1.351/Beta, B.1.617.2/Delta and BA.1.1/Omicron isolates and demonstrated heterogeneous infectivity and pathogenesis. B.1.351/Beta variant was the most pathogenic, while BA.1.1/Omicron led to lower viral RNA in the absence of major visible clinical signs. In parallel, we infected wildtype (WT) mice and confirmed that, contrary to B.1 and B.1.617.2/Delta, B.1.351/Beta and BA.1.1/Omicron can infect them. Infection in WT mice coursed without major clinical signs and viral RNA was transient and undetectable in the lungs by day 7 post-infection. In silico modeling supported these findings by predicting B.1.351/Beta receptor binding domain (RBD) mutations result in an increased affinity for both human and murine ACE2 receptors, while BA.1/Omicron RBD mutations only show increased affinity for murine ACE2., The research of CBIG consortium (constituted by IRTA-CReSA, BSC & IrsiCaixa) is supported by Grifols. We thank Foundation Dormeur for financial support for the acquisition of the QuantStudio-5 real time PCR system. CÁ-N has a grant by Secretaria d’Universitats i Recerca de la Generalitat de Catalunya and Fons Social Europeu. EG-V is a research fellow from PERIS (SLT017/20/000090). This work was partially funded by grant PID2020-117145RB-I00 from the Spanish Ministry of Science and Innovation (NI-U) the Departament de Salut of the Generalitat de Catalunya (grant SLD016 to JB and Grant SLD015 to JC), the Spanish Health Institute Carlos III (Grant PI17/01518. PI20/00093 to JB and PI18/01332 to JC), Fundació La Marató de TV3 (Project202126-30-21), CERCA Programme/Generalitat de Catalunya 2017 SGR 252, and the crowdfunding initiatives #joemcorono (https://www.yomecorono.com), BonPreu/Esclat and Correos. Funded in part by Fundació Glòria Soler (JB). The funders had no role in study design, data collection and analysis, the decision to publish, or the preparation of the manuscript., Peer Reviewed, "Article signat per 27 autors/es: Ferran Tarrés-Freixas, Benjamin Trinité, Anna Pons-Grífols, Miguel Romero-Durana, Eva Riveira-Muñoz, Carlos Ávila-Nieto, Mónica Pérez, Edurne Garcia-Vidal, Daniel Perez-Zsolt, Jordana Muñoz-Basagoiti, Dàlia Raïch-Regué, Nuria Izquierdo-Useros, Cristina Andrés, Andrés Antón, Tomàs Pumarola, Ignacio Blanco, Marc Noguera-Julián, Victor Guallar, Rosalba Lepore, Alfonso Valencia, Victor Urrea, Júlia Vergara-Alert, Bonaventura Clotet, Ester Ballana, Jorge Carrillo, Joaquim Segalés and Julià Blanco", Postprint (published version)