Inhalation therapy in the next decade : Determinants of adherence to treatment in asthma and COPD

Peer reviewedPublisher PD

Bovine lactoferrin-induced CCL1 expression involves distinct receptors in monocyte-derived dendritic cells and their monocyte precursors

Lactoferrin (LF) exhibits a wide range of immunomodulatory activities including modulation of cytokine and chemokine secretion. In this study, we demonstrate that bovine LF (bLF) up-modulates, in a concentration- and time-dependent manner, CCL1 secretion in monocytes (Mo) at the early stage of differentiation toward dendritic cells (DCs), and in fully differentiated immature Mo-derived DCs (MoDCs). In both cell types, up-modulation of CCL1 secretion is an early event following bLF-mediated enhanced accumulation of CCL1 transcripts. Notably, bLF-mediated up-regulation of CCL1 involves the engagement of distinct surface receptors in MoDCs and their Mo precursors. We show that bLF-mediated engagement of CD36 contributes to CCL1 induction in differentiating Mo. Conversely, toll-like receptor (TLR)2 blocking markedly reduces bLF-induced CCL1 production in MoDCs. These findings add further evidence for cell-specific differential responses elicited by bLF through the engagement of distinct TLRs and surface receptors. Furthermore, the different responses observed at early and late stages of Mo differentiation towards DCs may be relevant in mediating bLF effects in specific body districts, where these cell types may be differently represented in physiopathological conditions

Factores Pedagógicos que Favorecen el Éxito Escolar en Estudiantes de Enseñanza Postobligatoria

El foco del presente estudio ha sido el éxito escolar: la continuidad, la permanencia en el sistema educativo, lo cual implica transitar de forma adecuada por sus diversas etapas y modalidades formativas. En particular, hemos buscado conocer qué factores pedagógicos -vinculados a los procesos de enseñanza-aprendizaje y a la relación profesor/a-alumno/a- constituyen condiciones favorables para el éxito y la continuidad escolar de chicas y de chicos de enseñanza secundaria postobligatoria (Bachillerato y Ciclos Formativos). Hemos tratado de visibilizar el éxito escolar de chicos y de chicas en la educación secundaria, de analizar las experiencias y las trayectorias de estudiantes que, más allá del periodo obligatorio, dan continuidad a su vida escolar con éxito académico, de prestar atención a las diferencias entre estudiantes de Bachillerato y Ciclos Formativos y, por último, de analizar de forma diferenciada la experiencia de las chicas y de los chicos, indagando en los elementos de la construcción de la subjetividad en ambos sexos. Para ello, hemos trabajado con una muestra intencional de 26 estudiantes (12 chicas y 14 chicos), 16 de Bachillerato y 10 de Ciclos Formativos, seleccionados por sus docentes, en 12 centros urbanos y semiurbanos de Málaga, Sevilla, Granada, Cádiz y Almería. Los datos han sido recogidos a través de entrevistas semiestructuradas, con el apoyo de la técnica de foto-lenguaje y un cuestionario de contexto.Fundación Centro de Estudios Andaluces - [PRY031/11

Alzheimer's disease biomarker profiling in a memory clinic cohort without common comorbidities

Alzheimer's disease is a multifactorial disorder with large heterogeneity. Comorbidities such as hypertension, hypercholesterolaemia and diabetes are known contributors to disease progression. However, less is known about their mechanistic contribution to Alzheimer's pathology and neurodegeneration. The aim of this study was to investigate the relationship of several biomarkers related to risk mechanisms in Alzheimer's disease with the well-established Alzheimer's disease markers in a memory clinic population without common comorbidities. We investigated 13 molecular markers representing key mechanisms underlying Alzheimer's disease pathogenesis in CSF from memory clinic patients without diagnosed hypertension, hypercholesterolaemia or diabetes nor other neurodegenerative disorders. An analysis of covariance was used to compare biomarker levels between clinical groups. Associations were analysed by linear regression. Two-step cluster analysis was used to determine patient clusters. Two key markers were analysed by immunofluorescence staining in the hippocampus of non-demented control and Alzheimer's disease individuals. CSF samples from a total of 90 participants were included in this study: 30 from patients with subjective cognitive decline (age 62.4 ± 4.38, female 60%), 30 with mild cognitive impairment (age 65.6 ± 7.48, female 50%) and 30 with Alzheimer's disease (age 68.2 ± 7.86, female 50%). Angiotensinogen, thioredoxin-1 and interleukin-15 had the most prominent associations with Alzheimer's disease pathology, synaptic and axonal damage markers. Synaptosomal-associated protein 25 kDa and neurofilament light chain were increased in mild cognitive impairment and Alzheimer's disease patients. Grouping biomarkers by biological function showed that inflammatory and survival components were associated with Alzheimer's disease pathology, synaptic dysfunction and axonal damage. Moreover, a vascular/metabolic component was associated with synaptic dysfunction. In the data-driven analysis, two patient clusters were identified: Cluster 1 had increased CSF markers of oxidative stress, vascular pathology and neuroinflammation and was characterized by elevated synaptic and axonal damage, compared with Cluster 2. Clinical groups were evenly distributed between the clusters. An analysis of post-mortem hippocampal tissue showed that compared with non-demented controls, angiotensinogen staining was higher in Alzheimer's disease and co-localized with phosphorylated-tau. The identification of biomarker-driven endophenotypes in cognitive disorder patients further highlights the biological heterogeneity of Alzheimer's disease and the importance of tailored prevention and treatment strategies

Gene expression landscape of Chronic Myeloid Leukemia K562 cells overexpressing the tumor suppressor gene PTPRG

This study concerns the analysis of the modulation of Chronic Myeloid Leukemia (CML) cell model K562 transcriptome following transfection with the tumor suppressor gene encoding for Protein Tyrosine Phosphatase Receptor Type G (PTPRG) and treatment with the tyrosine kinase inhibitor (TKI) Imatinib. Specifically, we aimed at identifying genes whose level of expression is altered by PTPRG modulation and Imatinib concentration. Statistical tests as differential expression analysis (DEA) supported by gene set enrichment analysis (GSEA) and modern methods of ontological term analysis are presented along with some results of current interest for forthcoming experimental research in the field of the transcriptomic landscape of CML. In particular, we present two methods that differ in the order of the analysis steps. After a gene selection based on fold-change value thresholding, we applied statistical tests to select differentially expressed genes. Therefore, we applied two different methods on the set of differentially expressed genes. With the first method (Method 1), we implemented GSEA, followed by the identification of transcription factors. With the second method (Method 2), we first selected the transcription factors from the set of differentially expressed genes and implemented GSEA on this set. Method 1 is a standard method commonly used in this type of analysis, while Method 2 is unconventional and is motivated by the intention to identify transcription factors more specifically involved in biological processes relevant to the CML condition. Both methods have been equipped in ontological knowledge mining and word cloud analysis, as elements of novelty in our analytical procedure. Data analysis identified RARG and CD36 as a potential PTPRG up-regulated genes, suggesting a possible induction of cell differentiation toward an erithromyeloid phenotype. The prediction was confirmed at the mRNA and protein level, further validating the approach and identifying a new molecular mechanism of tumor suppression governed by PTPRG in a CML context

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Adaptation and use of technological tools for data processing in the Home of VAS for Linio Colombia

A partir de la investigación que se realizó se pudo concluir que hay una gran oportunidad de mejora para satisfacer las necesidades de los clientes, dicha oportunidad va ligada con la entrega de reportes para mejorar su visualización, entendimiento y orden ya que estos no estaban cumpliendo las expectativas y estaban dificultando la toma de decisiones estratégicas para los sellers. Todo esto se hizo a través de la creación de un dashboard por medio de la herramienta Power BI, a través de la cual luego de identificar la principal problemática que estaba enfrentando el área de VAS de Linio Colombia se llegó a la solución, y se creó un seguimiento de las campañas que pautan en esta, así como a la implementación de un dashboard para obtener una base de datos con informacion actualizada que en este momento está siendo de gran utilidad para la ejecución de reportes mensuales, ya que dicha información vendrá mucho más detallada, especifica y dinámica a la vista, lo cual facilitará el entendimiento de estos y ayudará a una mejor toma de decisiones para también lograr el cumplimiento de objetivos empresariales.From the investigation that was carried out, it was possible to conclude that there is a great opportunity for improvement to satisfy the needs of the clients, this opportunity is linked to the delivery of reports to improve their visualization, understanding and order since they were not complying with the expectations and were making it difficult for sellers to make strategic decisions. All this was done through the creation of a dashboard through the Power BI tool, through which, after identifying the main problem that the VAS area of Linio Colombia was facing, the solution was found, and this was to create a follow-up of the campaigns that guide this, as well as the implementation of a dashboard to obtain a database with updated information that at this moment is being very useful for the execution of monthly reports, since this information now will be more detailed, specific and dynamic in view, which will facilitate their understanding and help better decision making, to also achieve the fulfillment of business objectives.Administrador (a) de EmpresasPregrad