Immediate effects of dasatinib on the migration and redistribution of naïve and memory lymphocytes associated with lymphocytosis in chronic myeloid leukemia patients

Introduction: Dasatinib is a dual SRC/ABL tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML) that is known to have unique immunomodulatory effects. In particular, dasatinib intake typically causes lymphocytosis, which has been linked to better clinical response. Since the underlying mechanisms are unknown and SRC family kinases are involved in many cell motility processes, we hypothesized that the movement and migration of lymphocytes is modulated by dasatinib. Patients, Materials and Methods: Peripheral blood samples from CML patients treated with second-line dasatinib were collected before and 2 h after the first dasatinib intake, and follow-up samples from the same patients 3 and 6 months after the start of therapy. The migratory capacity and phenotype of lymphocytes and differential blood counts before and after drug intake were compared for all study time-points. Results: We report here for the first time that dasatinib intake is associated with inhibition of peripheral blood T-cell migration toward the homeostatic chemokines CCL19 and CCL21, which control the trafficking toward secondary lymphoid organs, mainly the lymph nodes. Accordingly, the proportion of lymphocytes in blood expressing CCR7, the chemokine receptor for both CCL19 and CCL21, decreased after the intake including both naïve CD45RA+ and central memory CD45RO+ T-cells. Similarly, naïve B-cells diminished with dasatinib. Finally, such changes in the migratory patterns did not occur in those patients whose lymphocyte counts remained unchanged after taking the drug. Discussion: We, therefore, conclude that lymphocytosis induced by dasatinib reflects a pronounced redistribution of naïve and memory populations of all lymphocyte subsets including CD4+ and CD8+ T-cells and B-cells

Statistical analysis to perform improvement actions in Final Degree Projects. A proposal for the Degree in Pharmacy

[EN] A statistical analysis of the most important characteristics of the Final Degree Projects (FDP) of the Degree in Pharmacy at the University of the Basque Country (UPV / EHU) has been carrying out. The sample analyzed was 264 FDP. The results of the analysis, a multivariate logistic regression, have confirmed, among other aspects, that a great majority of the FDP contain knowledge of a single module of the curriculum, and their content is usually not directly linked to any of job opportunities of the Degree. To reverse this trend, this paper proposes an intervention that resolves the observed deficiencies and improves the execution dynamics of the FDP. The proposal includes a working methodology of a teaching team that is involved and participates in the approach, elaboration, direction and evaluation of the FDP. In addition, an example of the methodology applied to job opportunity of the Community Pharmacy is presenting. The teaching team is multidisciplinary, formed by specialists in different subjects of all the courses of the Degree, of five areas of knowledge belonging to four of the six modules developed in the curriculum. The teaching team and the participating students work with a methodology of Problem Based Learning (PBL). This proposal strengthens the coordination of teaching teams, the originality and creativity of the FDP, the active role of students and teachers and a direct relationship with professional opportunities, which can be implementing in any degree. This work was financing by the UPV / EHU[ES] Se ha realizado un análisis estadístico de las características más importantes de los Trabajos de Fin de Grado (TFG) del Grado en Farmacia en la Universidad del País Vasco (UPV/EHU). La muestra analizada ha sido de 264 TFG. Los resultados del análisis, una regresión logística multivariante, han constatado, entre otros aspectos, que una gran mayoría de los TFG, contienen conocimientos de un único módulo del plan de estudios, y su contenido no suele estar directamente ligado a alguna de las salidas profesionales del Grado. Para revertir esta tendencia, en este trabajo se plantea una intervención que resuelva las carencias observadas y mejore la dinámica de ejecución de los TFG. La propuesta incluye una metodología de trabajo de un equipo docente que se involucra y participa en el planteamiento, elaboración, dirección y evaluación de los TFG. Además, se presenta un ejemplo de la metodología aplicada a la salida profesional de la Farmacia Comunitaria. El equipo docente es multidisciplinar, formado por especialistas en diversas materias de todos los cursos del Grado, de cinco áreas de conocimiento pertenecientes a cuatro de los seis módulos desarrollados en el plan de estudios. El equipo docente y el alumnado participante trabajan con una metodología de Aprendizaje Basado en Problemas (ABP). Esta propuesta, potencia la coordinación de equipos docentes, la originalidad y creatividad de los TFG, el protagonismo activo del alumnado y profesorado y una relación directa con las salidas profesionales, que puede implementarse en cualquier Grado. Este trabajo contó con la financiación de la UPV/EHU.Berraondo Juaristi, M.; Fernández De Aránguiz Guridi, MY.; Fernández De Aránguiz Guridi, A.; Ruiz Ortega, J.; Ayerbe Diaz, M.; Lecea Arana, B.; Martínez De Marigorta Izaga, E.... (2018). Análisis estadístico para realizar acciones de mejora en los Trabajos Fin de Grado. Una propuesta para el Grado en Farmacia. REDU. Revista de Docencia Universitaria. 16(2):17-38. doi:10.4995/redu.2018.9847SWORD173816

Spatial and temporal facies evolution of a Lower Jurassic carbonate platform, NW Tethyan margin (Mallorca, Spain)

The variety of depositional facies of a Lower Jurassic carbonate platform has been investigated on the island of Mallorca along a transect comprising six stratigraphic profiles. Twenty-nine facies and sub-facies have been recognized, grouped into seven facies associations, ranging in depositional environment from supratidal/terrestrial and peritidal to outer platform. Spatial and temporal (2D) facies distribution along the transect reflects the evolution of the carbonate platform with time showing different facies associations, from a broad peritidal platform (stage 1) to a muddy open platform (stage 2), and finally to a peritidal to outer carbonate platform (stage 3). Stage 1 (early Sinemurian to earliest late Sinemurian) corresponds to a nearly-flat peritidal-shallow subtidal epicontinental platform with facies belts that shifted far and fast over the whole study area. The evolution from stage 1 to stage 2 (late Sinemurian) represents a rapid flooding of the epicontinental shallow platform, with more open-marine conditions, and the onset of differential subsidence. During stage 3 (latest Sinemurian), peritidal and shallow-platform environments preferentially developed to the northeast (Llevant Mountains domain) with a rapid transition to middle-outer platform environments toward the northwest (Tramuntana Range domain). Stages 1 and 3 present facies associations typical of Bahamian-type carbonates, whereas stage 2 represents the demise of the Bahamian-type carbonate factory and proliferation of muddy substrates with suspension-feeders. The described platform evolution responded to the interplay between the initial extensional tectonic phases related to Early Jurassic Tethyan rifting, contemporaneous environmental perturbations, and progressive platform flooding related to the Late Triassic–Early Jurassic worldwide marine transgression and associated accommodation changes

Efficacy of a brief multifactorial adherence-based intervention on reducing the blood pressure of patients with poor adherence: protocol for a randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>Lowering of blood pressure by antihypertensive drugs reduces the risks of cardiovascular events, stroke, and total mortality. However, poor adherence to antihypertensive medications reduces their effectiveness and increases the risk of adverse events. In terms of relative risk reduction, an improvement in medication adherence could be as effective as the development of a new drug.</p> <p>Methods/Design</p> <p>The proposed randomized controlled trial will include patients with a low adherence to medication and uncontrolled blood pressure. The intervention group will receive a multifactorial intervention during the first, third, and ninth months, to improve adherence. This intervention will include motivational interviews, pill reminders, family support, blood pressure self-recording, and simplification of the dosing regimen.</p> <p>Measurement</p> <p>The primary outcome is systolic blood pressure. The secondary outcomes are diastolic blood pressure, proportion of patients with adequately controlled blood pressure, and total cost.</p> <p>Discussion</p> <p>The trial will evaluate the impact of a multifactorial adherence intervention in routine clinical practice. Ethical approval was given by the Ethical Committee on Human Research of Balearic islands, Spain (approval number IB 969/08 PI).</p> <p>Trial registration</p> <p>Current controlled trials ISRCTN21229328</p

Data Descriptor : A European Multi Lake Survey dataset of environmental variables, phytoplankton pigments and cyanotoxins

Under ongoing climate change and increasing anthropogenic activity, which continuously challenge ecosystem resilience, an in-depth understanding of ecological processes is urgently needed. Lakes, as providers of numerous ecosystem services, face multiple stressors that threaten their functioning. Harmful cyanobacterial blooms are a persistent problem resulting from nutrient pollution and climate-change induced stressors, like poor transparency, increased water temperature and enhanced stratification. Consistency in data collection and analysis methods is necessary to achieve fully comparable datasets and for statistical validity, avoiding issues linked to disparate data sources. The European Multi Lake Survey (EMLS) in summer 2015 was an initiative among scientists from 27 countries to collect and analyse lake physical, chemical and biological variables in a fully standardized manner. This database includes in-situ lake variables along with nutrient, pigment and cyanotoxin data of 369 lakes in Europe, which were centrally analysed in dedicated laboratories. Publishing the EMLS methods and dataset might inspire similar initiatives to study across large geographic areas that will contribute to better understanding lake responses in a changing environment.Peer reviewe

Stratification strength and light climate explain variation in chlorophyll a at the continental scale in a European multilake survey in a heatwave summer

To determine the drivers of phytoplankton biomass, we collected standardized morphometric, physical, and biological data in 230 lakes across the Mediterranean, Continental, and Boreal climatic zones of the European continent. Multilinear regression models tested on this snapshot of mostly eutrophic lakes (median total phosphorus [TP] = 0.06 and total nitrogen [TN] = 0.7 mg L−1), and its subsets (2 depth types and 3 climatic zones), show that light climate and stratification strength were the most significant explanatory variables for chlorophyll a (Chl a) variance. TN was a significant predictor for phytoplankton biomass for shallow and continental lakes, while TP never appeared as an explanatory variable, suggesting that under high TP, light, which partially controls stratification strength, becomes limiting for phytoplankton development. Mediterranean lakes were the warmest yet most weakly stratified and had significantly less Chl a than Boreal lakes, where the temperature anomaly from the long-term average, during a summer heatwave was the highest (+4°C) and showed a significant, exponential relationship with stratification strength. This European survey represents a summer snapshot of phytoplankton biomass and its drivers, and lends support that light and stratification metrics, which are both affected by climate change, are better predictors for phytoplankton biomass in nutrient-rich lakes than nutrient concentrations and surface temperature

Evaluación del Practicum en industria del Master Universitario de Investigación, Desarrollo y Control de Medicamentos

Podeu consultar la Setena trobada de professorat de Ciències de la Salut completa a: http://hdl.handle.net/2445/43352El principal objetivo de este estudio, que forma parte del proyecto REDICE2010, fue evaluar el practicum de industria del Máster Universitario de Investigación, Desarro-llo y Control de Medicamentos, que se imparte en la Facultad de Farmacia de la UB y su repercusión en las asignaturas relacionadas. Dado que este período de prácticas, que se realiza en una industria del sector far-macéutico o afín, debe proporcionar al alumnado competencias y habilidades que les capacitan para la actividad profesional, se ha recabado la opinión tanto de los estudiantes (actuales y egresados del máster) como de los tutores de la industria y de la universidad y de expertos en el sector industrial y académico que aportan su visión sobre la formación idónea de los alumnos para afrontar con éxito los retos profesionales, a fin de detectar debilidades formativas en el máster y establecer mecanismos de mejora

Preclinical characterization of antagomiR-218 as a potential treatment for myotonic dystrophy

Myotonic dystrophy type 1 (DM1) is a rare neuromuscular disease caused by expansion of unstable CTG repeats in a non-coding region of the DMPK gene. CUG expansions in mutant DMPK transcripts sequester MBNL1 proteins in ribonuclear foci. Depletion of this protein is a primary contributor to disease symptoms such as muscle weakness and atrophy and myotonia, yet upregulation of endogenous MBNL1 levels may compensate for this sequestration. Having previously demonstrated that antisense oligonucleotides against miR-218 boost MBNL1 expression and rescue phenotypes in disease models, here we provide preclinical characterization of an antagomiR-218 molecule using the HSALR mouse model and patient-derived myotubes. In HSALR, antagomiR-218 reached 40–60 pM 2 weeks after injection, rescued molecular and functional phenotypes in a dose- and time-dependent manner, and showed a good toxicity profile after a single subcutaneous administration. In muscle tissue, antagomiR rescued the normal subcellular distribution of Mbnl1 and did not alter the proportion of myonuclei containing CUG foci. In patient-derived cells, antagomiR-218 improved defective fusion and differentiation and rescued up to 34% of the gene expression alterations found in the transcriptome of patient cells. Importantly, miR-218 was found to be upregulated in DM1 muscle biopsies, pinpointing this microRNA (miRNA) as a relevant therapeutic target

Informe final de l'avaluació d'impacte als entorns escolars pacificats a la ciutat de Barcelona pel programa Protegim les Escoles. Període, 2021-2023

Unidad de excelencia María de Maeztu CEX2019-000940-MAquest estudi forma part de la Iniciativa de Planificació Urbana, Medi Ambient i Salut del ISGlobal, dirigida per Mark Nieuwenhuijsen i coordinada per la Carolyn Daher.Aquest informe resumeix l'impacte de les pacificacions implementades en el 2021 i el 2022-2023 pel Programa Protegim Les Escoles a la ciutat de Barcelona, que té com a objectiu transformar entorns escolars en nous espais més segurs i saludables per a tota la comunitat. Objectiu i metodologia. L'objectiu general de l'estudi és fer una avaluació d'impacte de les pacificacions implementades en els entorns escolars en el flux de trànsit motoritzat i vianants, l'ús de l'espai públic, el joc al carrer fora de l'horari d'entrada i sortida de les escoles, i la qualitat de l'aire. Aquesta metodologia recull així els canvis en l'ús de l'espai públic i qualitat ambiental, pels infants i les seves famílies, però també per la resta de la comunitat. L'estudi es basa en observacions sistemàtiques i percepcions de l'espai públic, en horari de matí (10:00-12:00) i tarda (17:00-19:00), així com mesures de la qualitat de l'aire (nivells de NO2) realitzades abans i després d'implementar les pacificacions en entorns escolars, comparant-los amb entorns de control similars on no s'han fet actuacions. Aquesta metodologia ens permet entendre millor quins canvis estan directament relacionats amb les intervencions i fer millores per a futures accions. Conclusions. Cal emmarcar les transformacions i l'avaluació d'impacte coincidint en un context d'incertesa de sortida del desconfinament i restriccions d'ús de l'espai públic per la Covid-19 durant el 2021, en el que de manera gradual es va anar recuperant l'ús del carrer, la interacció social, la percepció del benestar general i de l'entorn. Aquesta situació pot haver influenciat alguns dels indicadors i resultats durant el període d'avaluació. Les principals conclusions de l'estudi es resumeixen en els següents punts: Les pacificacions dels entorns escolars han creat espais de convivència més inclusius i saludables per als nens i nenes i la resta de la comunitat. Les pacificacions totals (Carrers Escola) han reduït significativament el flux de trànsit motoritzat (sobretot cotxes i motos), augmentat l'ús de l'espai públic per tota la comunitat i promogut el joc al carrer, especialment a la tarda. La reducció del trànsit motoritzat ha augmentat l'activitat física i les relacions socials entre els infants, especialment en les nenes, contribuint a millorar la seva salut física i emocional. Les pacificacions han contribuït a una millora en la qualitat de l'aire, amb una reducció dels nivells de NO2, beneficiant la salut respiratòria, cardiovascular i neurològica de la població. L'ús de l ́espai públic, el joc al carrer i la proporció de nenes jugant ha augmentat en les pacificacions parcials implementades en el 2022-2023, probablement en relació amb adaptacions realitzades respecte a les del 2021 i a un efecte de consolidació de les transformacions. Les pacificacions parcials implementades en el 2022-2023 consoliden els resultats de les anteriors, implementades en el 2021, en quant a l'augment en el flux de vianants, la reducció del flux de trànsit motoritzat i millora de la qualitat de l'aire. En general les percepcions de les persones usuàries de l'espai públic han millorat després de les transformacions a tots els entorns, destaca la millora de la percepció de seguretat als xamfrans. L'extensió limitada de les àrees transformades, la seva ubicació i probablement els criteris de selecció per ser els entorns pacificats, condicionen el recompte de persones usuàries i vehicles circulant i, per tant, la magnitud dels canvis observats atribuïbles a les pacificacions. Implementar mesures de pacificació més contundents en àrees de major extensió, juntament amb d'altres complementàries als carrers del voltant de les escoles contribuirà a escalar els resultats observats i maximitzar els beneficis en salut i seguretat associats. L'avaluació d'impacte adequada, des de la fase de disseny dels programes d'intervenció urbana, és crucial per atribuir els canvis observats a les intervencions implementades. El programa Protegim Les Escoles és una peça clau per aconseguir una ciutat pacificada i saludable, com a eina de transformació per poblacions vulnerables i tota la ciutadania