Neuropsychological Rehabilitation in Pediatric Oncology: comparison of neuropsychological profiles after intervention

Presentamos el caso de una adolescente diagnosticada en 2001 con un linfoma de Burkitt no-Hodgkin cuando tenía 14 años (etapa 4, CNS afectado). El tratamiento incluyó quimioterapia sistémica intratecal y radioterapia holocraneal (24Gy). En los estudios de imagen se aprecian cambios de señal en sustancia blanca frontal relacionados con la terapéutica. Participantes y Métodos: La paciente fue evaluada con nuestro protocolo de evaluación neuropsicológica que abarca múltiples funciones cognitivas, así como una evaluación psicopatológica. En septiembre de 2003 presenta un deterioro cognitivo generalizado. La rehabilitación se basó en su perfil neuropsicológico, edad, expectativas e intereses del paciente. La intervención específica en habilidades académicas se decidió debido a su retraso con sus compañeros. La intervención se ha llevado a cabo durante 10 meses, 2 horas / semana e incluye: técnicas y hábitos de estudio, capacitación habilidades académicas (aritmética, lectura, ejercicios de comprensión y escritura), atención y memoria. Los resultados de la evaluación neuropsicológica 2004 revelaron cambios significativos, entre 1 y 2 desviaciones estándar, en las áreas de intervención. Además se obtuvieron mejorías entre 12 y 19 puntos en los coeficientes intelectuales. Conclusiones: La rehabilitación en oncología pediátrica implica un apoyo a largo plazo para nuestros pacientes. Además de la mejora de los recursos ambientales (escuela, familia, servicios sociales...), queremos desarrollar intervenciones individualizadas que nos permite paliar / compensar las secuelas cáncer y su tratamiento. Estos primeros resultados ofrecen mejoras significativas y cuantificables en las áreas de intervención y son un primer indicador de la validez de nuestro trabajo.We present the case of an adolescent diagnosed in 2001 with a Non-Hodgkin Burkitt's lymphoma when she was 14 (stage 4, CNS affected). Treatment included systemic and intrathecal chemotherapy and holocranial radiotherapy (24Gy). Imaging studies revealed signal changes in frontal white matter related with therapeutics. Participants and Methods : The patient was assessed with our neuropsychological assessment protocol composed of multiple cognitive functioning as well as a psychopathological evaluation. In September 2003 she presented a generalized cognitive deterioration. Rehabilitation was based on her neuropsychological profile, age, expectations and interests of the patient. Specific intervention in academic abilities was decided because of her delay with peers. The intervention has been carried out for 10 months, 2 hours/week and included: techniques and studying habits, academic abilities training (arithmetic, reading comprehension and writing), attention and memory exercises. Results : Results of 2004 neuropsychological assessment revealed significant changes, between 1 and 2 standard deviations, in the intervention areas. Moreover we obtained 12 to 19 points improvement in IQ. Conclusions : Rehabilitation in pediatric oncology implies long-term support for our patients. Besides of improving environmental resources (school, family, social services...), we want to develop individualized interventions that allows us to palliate/compensate cancer and treatment sequelae. These first results offer significant and quantitative improvements in the intervention areas and are the first to point out the validity of our work

Hif-1α knockdown reduces glycolytic metabolism and induces cell death of human synovial fibroblasts under normoxic conditions

[Abstract] Increased glycolysis and HIF-1α activity are characteristics of cells under hypoxic or inflammatory conditions. Besides, in normal O2 environments, elevated rates of glycolysis support critical cellular mechanisms such as cell survival. The purpose of this study was to analyze the contribution of HIF-1α to the energy metabolism and survival of human synovial fibroblasts (SF) under normoxic conditions. HIF-1α was silenced using lentiviral vectors or small-interfering RNA (siRNA) duplexes. Expression analysis by qRT-PCR and western blot of known HIF-1α target genes in hypoxia demonstrated the presence of functional HIF-1α in normoxic SF and confirmed the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a HIF-1α target even in normoxia. HIF-1α silencing induced apoptotic cell death in cultured SF and, similarly, treatment with glycolytic, but not with OXPHOS inhibitors, induced SF death. Finally, in vivo HIF-1α targeting by siRNA showed a significant reduction in the viability of human SF engrafted into a murine air pouch. Our results demonstrate that SF are highly dependent on glycolytic metabolism and that HIF-1α plays a regulatory role in glycolysis even under aerobic conditions. Local targeting of HIF-1α provides a feasible strategy to reduce SF hyperplasia in chronic arthritic diseases.Instituto de Salud Carlos III; FIS 12/439Instituto de Salud Carlos III; RETICS RD12/009Instituto de Salud Carlos III; CP13/00014Comunidad de Madrid; RAPHYME-CM S2010/BMD235

CD38 Deficiency Ameliorates Chronic Graft-Versus-Host Disease Murine Lupus via a B-Cell-Dependent Mechanism

© 2021 Martínez-Blanco, Domínguez-Pantoja, Botía-Sánchez, Pérez-Cabrera, Bello-Iglesias, Carrillo-Rodríguez, Martin-Morales, Lario-Simón, Pérez-Sánchez-Cañete, Montosa-Hidalgo, Guerrero-Fernández, Longobardo-Polanco, Redondo-Sánchez, Cornet-Gomez, Torres-Sáez, Fernández-Ibáñez, Terrón-Camero, Andrés-León, O’Valle, Merino, Zubiaur and Sancho.The absence of the mouse cell surface receptor CD38 in Cd38−/− mice suggests that this receptor acts as a positive regulator of inflammatory and autoimmune responses. Here, we report that, in the context of the chronic graft-versus-host disease (cGVHD) lupus inducible model, the transfer of B6.C-H2bm12/KhEg(bm12) spleen cells into co-isogenic Cd38−/− B6 mice causes milder lupus-like autoimmunity with lower levels of anti-ssDNA autoantibodies than the transfer of bm12 spleen cells into WT B6 mice. In addition, significantly lower percentages of Tfh cells, as well as GC B cells, plasma cells, and T-bet+CD11chi B cells, were observed in Cd38−/− mice than in WT mice, while the expansion of Treg cells and Tfr cells was normal, suggesting that the ability of Cd38−/− B cells to respond to allogeneic help from bm12 CD4+ T cells is greatly diminished. The frequencies of T-bet+CD11chi B cells, which are considered the precursors of the autoantibody-secreting cells, correlate with anti-ssDNA autoantibody serum levels, IL-27, and sCD40L. Proteomics profiling of the spleens from WT cGVHD mice reflects a STAT1-driven type I IFN signature, which is absent in Cd38−/− cGVHD mice. Kidney, spleen, and liver inflammation was mild and resolved faster in Cd38−/− cGVHD mice than in WT cGVHD mice. We conclude that CD38 in B cells functions as a modulator receptor that controls autoimmune responses.S and MZ received financial support through “Proyecto del Plan Estatal”: SAF2017–89801-R. The IPBLN-CSIC Proteomics Unit belonged to ProteoRed-ISCIII (PRB2; PRB3) and was supported by grants PT13/0001/0011 (IPBLN-CSIC) and PT17/0019/0010 (CIB-CSIC; IPBLN-CSIC). RM: Project: SAF2017-82905-R. FO'V: Cátedra MIS IMPLANT-UGR. The stay of AC-G in Sancho’s lab was supported by a fellowship-contract JAE-Intro (CSIC). The stay of MD-P in Sancho’s lab was supported by a 1-year post-doctoral fellowship (Reference No. 502492) from the Consejo Nacional de Ciencia y Tecnología (CONACYT) of México. EA-L was recipient of a postdoctoral fellowship from the regional Andalusian Government

Physical fitness reference standards for preschool children: the PREFIT project

Objectives: Reference values are necessary for classifying children, for health screening, and for early prevention as many non-communicable diseases aggravate during growth and development. While physical fitness reference standards are available in children aged 6 and older, such information is lacking in preschool children. Therefore, the purposes of this study were (1) to provide sex-and age-specific physical fitness reference standards for Spanish preschool children; and (2) to study sex differences across this age period and to characterise fitness performance throughout the preschool period. Design: Cross-sectional. Methods: A total of 3179 preschool children (1678 boys) aged 2.8–6.4 years old from Spain were included in the present study. Physical fitness was measured using the PREFIT battery. Results: Age- and sex-specific percentiles for the physical fitness components are provided. Boys performed better than girls in the cardiorespiratory fitness, muscular strength, and speed-agility tests over the whole preschool period studied and for the different percentiles. In contrast, girls performed slightly better than boys in the balance test. Older children had better performance in all fitness tests than their younger counterparts. Conclusions: Our study provides age- and sex-specific physical fitness reference standards in preschool children allowing interpretation of fitness assessment. Sexual dimorphism in fitness tests exists already at preschool age, and these differences become larger with age. These findings will help health, sport, and school professionals to identify preschool children with a high/very low fitness level, to examine changes in fitness over time, and to analyse those changes obtained due to intervention effects.The PREFIT project takes place thanks to the funding linked to the Ramón y Cajal grant held by FBO (RYC-2011-09011). CC-S is supported by a grant from the Spanish Ministry of Economy and Competitiveness (BES-2014-068829). JRR and FBO are supported by grants from the Spanish Ministry of Science and Innovation (RYC-2010-05957 and RYC-2011-09011, respectively). In addition, this study was further supported by the University of Granada, Plan Propio de Investigación 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES). Additional funding from the SAMID III network, RETICS, funded by the PNI+D+I 2017-2021 (Spain), ISCIII- Sub-Directorate General for Research Assessment and Promotion, the European Regional Development Fund (ERDF) (Ref. RD16/0022), the EXERNET Research Network on Exercise and Health in Special Populations (DEP2005-00046/ACTI), the University of the Basque Country (GIU14/21), and the University of Zaragoza (JIUZ-2014-BIO-08)

Extracellular vesicles from pristane-treated CD38-deficient mice express an antiinflammatory neutrophil protein signature, which reflects the mild lupus severity elicited in these mice

In CD38-deficient (Cd38-/-) mice intraperitoneal injection of pristane induces a lupus-like disease, which is milder than that induced in WT mice, showing significant differences in the inflammatory and autoimmune processes triggered by pristane. Extracellular vesicles (EV) are present in all body fluids. Shed by cells, their molecular make-up reflects that of their cell of origin and/or tissue pathological situation. The aim of this study was to analyze the protein composition, protein abundance, and functional clustering of EV released by peritoneal exudate cells (PECs) in the pristane experimental lupus model, to identify predictive or diagnostic biomarkers that might discriminate the autoimmune process in lupus from inflammatory reactions and/or normal physiological processes. In this study, thanks to an extensive proteomic analysis and powerful bioinformatics software, distinct EV subtypes were identified in the peritoneal exudates of pristane-treated mice: 1) small EV enriched in the tetraspanin CD63 and CD9, which are likely of exosomal origin; 2) small EV enriched in CD47 and CD9, which are also enriched in plasma-membrane, membrane-associated proteins, with an ectosomal origin; 3) small EV enriched in keratins, ECM proteins, complement/coagulation proteins, fibrin clot formation proteins, and endopetidase inhibitor proteins. This enrichment may have an inflammation-mediated mesothelial-tomesenchymal transition origin, representing a protein corona on the surface of peritoneal exudate EV; 4) HDL-enriched lipoprotein particles. Quantitative proteomic analysis allowed us to identify an anti-inflammatory, Annexin A1- enriched pro-resolving, neutrophil protein signature, which was more prominent in EV from pristane-treated Cd38-/- mice, and quantitative differences in the protein cargo of the ECM-enriched EV from Cd38-/- vs WT mice. These differences are likely to be related with the distinct inflammatory outcome shown by Cd38-/- vs WT mice in response to pristane treatment. Our results demonstrate the power of a hypothesis-free and data-driven approach to transform the heterogeneity of the peritoneal exudate EV from pristanetreated mice in valuable information about the relative proportion of different EV in a given sample and to identify potential protein markers specific for the different small EV subtypes, in particular those proteins defining EV involved in the resolution phase of chronic inflammation.Proyecto del plan estatal, Ministerio de Ciencia e Innovacion PT13/0001/011CSIC PT17/0019/0010 PID2020-119567RB-I0

A deletion at Adamts9-magi1 Locus is associated with psoriatic arthritis risk

Objective: Copy number variants (CNVs) have been associated with the risk to develop multiple autoimmune diseases. Our objective was to identify CNVs associated with the risk to develop psoriatic arthritis (PsA) using a genome-wide analysis approach. Methods: A total of 835 patients with PsA and 1498 healthy controls were genotyped for CNVs using the Illumina HumanHap610 BeadChip genotyping platform. Genomic CNVs were characterised using CNstream analysis software and analysed for association using the χ2 test. The most significant genomic CNV associations with PsA risk were independently tested in a validation sample of 1133 patients with PsA and 1831 healthy controls. In order to test for the specificity of the variants with PsA aetiology, we also analysed the association to a cohort of 822 patients with purely cutaneous psoriasis (PsC). Results: A total of 165 common CNVs were identified in the genome-wide analysis. We found a highly significant association of an intergenic deletion between ADAMTS9 and MAGI1 genes on chromosome 3p14.1 (p=0.00014). Using the independent patient and control cohort, we validated the association between ADAMTS9-MAGI1 deletion and PsA risk (p=0.032). Using next-generation sequencing, we characterised the 26 kb associated deletion. Finally, analysing the PsC cohort we found a lower frequency of the deletion compared with the PsA cohort (p=0.0088) and a similar frequency to that of healthy controls (p>0.3). Conclusions: The present genome-wide scan for CNVs associated with PsA risk has identified a new deletion associated with disease risk and which is also differential from PsC risk

The FLUXNET2015 dataset and the ONEFlux processing pipeline for eddy covariance data

The FLUXNET2015 dataset provides ecosystem-scale data on CO2, water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe (over 1500 site-years, up to and including year 2014). These sites, independently managed and operated, voluntarily contributed their data to create global datasets. Data were quality controlled and processed using uniform methods, to improve consistency and intercomparability across sites. The dataset is already being used in a number of applications, including ecophysiology studies, remote sensing studies, and development of ecosystem and Earth system models. FLUXNET2015 includes derived-data products, such as gap-filled time series, ecosystem respiration and photosynthetic uptake estimates, estimation of uncertainties, and metadata about the measurements, presented for the first time in this paper. In addition, 206 of these sites are for the first time distributed under a Creative Commons (CC-BY 4.0) license. This paper details this enhanced dataset and the processing methods, now made available as open-source codes, making the dataset more accessible, transparent, and reproducible.Peer reviewe

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions