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Risk of diabetes in patients with sleep apnea: comparison of surgery versus CPAP in a long-term follow-up study
Get PDFThis study aimed to obtain a comprehensive view of the risk of developing diabetes in patients with obstructive sleep apnea (OSA) and to compare this risk between patients receiving continuous positive airway pressure (CPAP) therapy versus upper airway surgery (UAS). We used local and the global-scale federated data research network TriNetX to obtain access to electronic medical records, including those for patients diagnosed with OSA, from health-care organizations (HCOs) worldwide. Using propensity score matching and the score-matched analyses of data for 5 years of follow-up, we found that patients who had undergone UAS had a lower risk of developing diabetes than those who used CPAP (risk ratio 0.415, 95% confidence interval (CI) 0.349-0.493). The risk for newly diagnosed diabetes patients showed a similar pattern (hazard ratio 0.382; 95% CI 0.317-0.459). Both therapies seem to protect against diabetes (Risk 0.081 after UAS vs. 0.195 after CPAP). Analysis of the large data sets collected from HCOs in Europe and globally lead us to conclude that, in patients with OSA, UAS can prevent the development of diabetes better than CPAP
MicroRNA-27a-3p targets FoxO signalling to induce tumour-like phenotypes in bile duct cells
No full textBackground & Aims: Cholangiocarcinoma (CCA) is a heterogeneous and lethal malignancy, the molecular origins of which remain poorly understood. MicroRNAs (miRs) target diverse signalling pathways, functioning as potent epigenetic regulators of tran-scriptional output. We aimed to characterise miRNome dysregulation in CCA, including its impact on transcriptome homeostasis and cell behaviour.Methods: Small RNA sequencing was performed on 119 resected CCAs, 63 surrounding liver tissues, and 22 normal livers. High -throughput miR mimic screens were performed in three primary human cholangiocyte cultures. Integration of patient tran-scriptomes and miRseq together with miR screening data identified an oncogenic miR for characterization. MiR-mRNA in-teractions were investigated by a luciferase assay. MiR-CRISPR knockout cells were generated and phenotypically characterized in vitro (proliferation, migration, colony, mitochondrial function, glycolysis) and in vivo using subcutaneous xenografts.Results: In total, 13% (140/1,049) of detected miRs were differentially expressed between CCA and surrounding liver tissues, including 135 that were upregulated in tumours. CCA tissues were characterised by higher miRNome heterogeneity and miR biogenesis pathway expression. Unsupervised hierarchical clustering of tumour miRNomes identified three subgroups, including distal CCA-enriched and IDH1 mutant-enriched subgroups. High-throughput screening of miR mimics uncovered 71 miRs that consistently increased proliferation of three primary cholangiocyte models and were upregulated in CCA tissues regardless of anatomical location, among which only miR-27a-3p had consistently increased expression and activity in several cohorts. FoxO signalling was predominantly downregulated by miR-27a-3p in CCA, partially through targeting of FOXO1. MiR-27a knockout increased FOXO1 levels in vitro and in vivo, impeding tumour behaviour and growth.Conclusions: The miRNomes of CCA tissues are highly remodelled, impacting transcriptome homeostasis in part through regulation of transcription factors like FOXO1. MiR-27a-3p arises as an oncogenic vulnerability in CCA
Chronic docosahexaenoic acid supplementation improves metabolic plasticity in subcutaneous adipose tissue of aged obese female mice
No full textThis study aimed to characterize the potential beneficial effects of chronic docosahexaenoic acid (DHA) supplementation on restoring subcutaneous
white adipose tissue (scWAT) plasticity in obese aged female mice. Two-month-old female C57BL/6J mice received a control (CT) or a high fat diet (HFD)
for 4 months. Then, 6-month-old diet-induced obese (DIO) mice were distributed into the DIO and the DIOMEG group (fed with a DHA-enriched HFD)
up to 18 months. In scWAT, the DHA-enriched diet reduced the mean adipocyte size and reversed the upregulation of lipogenic genes induced by the
HFD, reaching values even lower than those observed in CT animals. DIO mice exhibited an up-regulation of lipolytic and fatty oxidation gene expressions
that was reversed in DHA-supplemented mice except for Cpt1a mRNA levels, which were higher in DIOMEG as compared to CT mice. DHA restored the
increase of proinflammatory genes observed in scWAT of DIO mice. While no changes were observed in total macrophage F4/80+/CD11b+ content, the DHA
treatment switched scWAT macrophages profile by reducing the M1 marker Cd11c and increasing the M2 marker CD206. These events occurred alongside
with a stimulation of beige adipocyte specific genes, the restoration of UCP1 and pAKT/AKT ratio, and a recovery of the HFD-induced Fgf21 upregulation. In
summary, DHA supplementation induced a metabolic remodeling of scWAT to a healthier phenotype in aged obese mice by modulating genes controlling
lipid accumulation in adipocytes, reducing the inflammatory status, and inducing beige adipocyte markers in obese aged mice
Analysis and modelling of the dynamic stiffness up to 400 Hz of an air spring with a pipeline connected to a reservoir
No full textThe present research addresses the dynamic behaviour of an air spring with a pipeline connected
to a reservoir in a frequency range up to 400 Hz, in which structure-borne vibration transmission
may occur due to both the structural behaviour of the bellows and fluid dynamics in the
pneumatic circuit of the suspension. Based on experimental results, three frequency ranges are
distinguished where different resonances of the suspension appear: low (up to 30 Hz) due to
the air flow between the bellows and the surge reservoir, intermediate (30–150 Hz) due to the
formation of standing waves in the pipeline and high (beyond 150 Hz) due to the structural
dynamics of the bellows. A novel modelling technique to predict the dynamic behaviour of
the pneumatic system in all these frequency ranges is presented and validated: this consists of
an enhanced Finite Element Model (FEM) considering the structural properties of the bellows
and the effect of pressurised air in the bellows and in the reservoir, coupled to a model of
fluid exchange between the two main air volumes which is defined using a VUFLUIDECH
user subroutine developed in ABAQUS. The study focusses on the axial dynamic stiffness of
the pneumatic suspension, which plays a key role in determining the transmissibility of the
suspension. However, the mathematical model introduced in the paper is capable of predicting
also the vibration modes of the suspension in shear and rotation, which may be relevant in
some applications, e.g. when air springs are used in vehicle suspensions
¿Es necesario seguir investigando sobre la muerte? Una reflexión historiográfica y nuevas perspectivas
No full textLa historiografía sobre la muerte, desarrollada entre finales de los años setenta y noventa de la pasada centuria, tuvo especial interés y proyección a partir de las investigaciones trazadas por la tercera generación de Annales. Los planteamientos de esta corriente, en sintonía con los modelos de dicha escuela y avalados por la renovación del objeto histórico tras el estructuralismo, giraron alrededor del estudio de las condiciones materiales, actitudes, imágenes y gestualidad del hombre medieval ante la muerte. El cuerpo de esta fructífera reflexión, como parcela de la ¿historia de las mentalidades¿, albergó novedades metodológicas, facilitando una visión y proyección heurística, debido al impacto que tuvo dentro del diálogo de la historia con las ciencias sociales y otras disciplinas del quehacer humanístico. A finales del siglo xx y comienzo del presente, el giro producido en el quehacer histórico ha otorgado un mayor protagonismo a lo social y cultural, colocando en el lugar protagonista ocupado durante décadas por la ¿historia de la muerte¿ otros intereses. Compete, por tanto, plantearse qué horizontes cabría dibujar, dentro de las coordenadas historiográficas de la actualidad, para las investigaciones sobre la muerte, cuyas paradojas siguen vigentes como recurso para conocer los fenómenos y manifestaciones propias de la civilización medieval
Hitz, Zena, Pensativos. Los placeres ocultos de la vida intelectual, Madrid, Ediciones Encuentro, 2022, 243p. ISBN: 978-84-1339-110-6, 20,90€ [RESEÑA]
Get PDFBook Revie
Pablo Echart, Cine dentro del cine. 50 películas sobre el séptimo arte, Published by Editorial UOC, Barcelona (2023), 212 pp. [RECENSIÓN]
No full textBook Revie
Desarrollo de un método de cribado de fármacos para identificar nuevas drogas capaces de revertir el fenotipo resistente de las células cancerosas a la destrucción por células CAR-T.
Get PDFEn los últimos años, la terapia de células T con receptor de antígeno quimérico (CAR) se
ha convertido en un tratamiento prometedor para el tratamiento del cáncer. A pesar de
este progreso, una proporción significativa de pacientes experimenta resistencia a la
terapia CAR-T. Las células cancerosas pueden ser insensibles a la destrucción por las
células CAR-T, lo que se conoce como resistencia intrínseca. Esta resistencia intrínseca
es responsable de una parte muy significativa del fracaso de este tipo de terapias que
afecta a todo tipo de tumores, siendo una dificultad adicional para la eficacia de las células
CAR-T en el tratamiento de tumores sólidos. Mucho de los mecanismos de resistencia
intrínseca están regulados a nivel epigenético. Recientemente, se han desarrollado y
probado varios inhibidores epigenéticos en cáncer. El enfoque principal de la mayoría de
los estudios hasta ahora ha sido el efecto citotóxico directo de estos compuestos, y pocos
estudios han investigado la capacidad de revertir el fenotipo resistente de las células
cancerosas a la terapia CAR-T. Existe la necesidad de una metodología sistemática para
identificar nuevas drogas que sensibilicen a la célula tumoral a la destrucción por las
células CAR-T. Mediante la expresión de flaying luciferase (fLuc) en líneas murinas de
tumores sólidos que expresan el antígeno EGFRvIII, hemos establecido un protocolo
simple, preciso, sensible y robusto para detectar sensibilizadores epigenéticos.
Demostramos la eficacia de nuestro protocolo e identificamos varios inhibidores
epigenéticos capaces de sensibilizar a las células tumorales a la destrucción por un CAR
anti-EGFRvIII
Characterization of potential therapeutic targets in Leishmania infantum
Get PDFLeishmaniasis is a parasitic disease caused by various species of Leishmania, which affects
millions of people worldwide. Current treatments for leishmaniasis often present adverse
effects and may not be effective against every Leishmania strain or form of the disease.
Therefore, it is essential to explore new therapeutic approaches to combat the parasite. In this
study, we focused on the PeBoW complex proteins homologous in Leishmania, which is
involved in ribosomal biogenesis and plays a critical role in cancer development in mammalian
cells. Recently, a homologue of the oncogene PES1 was found in Leishmania major, which
plays a crucial role in parasite infectivity. Given this, we analyzed the possibility of using other
PeBoW complex partner genes in Leishmania as therapeutic targets for leishmaniasis treatment.
Specifically, our investigation aimed to characterize the partner WDR12 homologous in
Leishmania infantum (LmjWDR12) as new therapeutic approach
ECG, an essential tool to guide arrhythmic mitral valve prolapse diagnosis
Get PDFA 35-year-old man was referred for cardiac check-up because of
suspected reflex syncope. He underwent a tilt-test challenge without
syncope provocation. The electrocardiography (ECG) showed sinus
rhythm with polymorphic premature ventricular contractions (PVC),
with right bundle branch block morpholog