¿Existe una personalidad jaquecosa?.

Se revisa brevemente el concepto actual de jaqueca y se analiza detalladamente la literatura existente sobre la personalidad jaquecosa. El concepto de personalidad jaquecosa fue mantenido por clínicos y autores de orientación psicoanalítica en las décadas de 1930-1950. los estudios recientes efectuados con criterios epidemiológicos (no basados en estudios hospitalarios) y realizados, empleando tests psicológicos estandarizados no son concordantes con la existencia de una personalidad jaquecosa

¿Existe una personalidad jaquecosa?.

Se revisa brevemente el concepto actual de jaqueca y se analiza detalladamente la literatura existente sobre la personalidad jaquecosa. El concepto de personalidad jaquecosa fue mantenido por clínicos y autores de orientación psicoanalítica en las décadas de 1930-1950. los estudios recientes efectuados con criterios epidemiológicos (no basados en estudios hospitalarios) y realizados, empleando tests psicológicos estandarizados no son concordantes con la existencia de una personalidad jaquecosa

ISG15 and ISGylation is required for pancreatic cancer stem cell mitophagy and metabolic plasticity

Pancreatic cancer stem cells (PaCSCs) drive pancreatic cancer tumorigenesis, chemoresistance and metastasis. While eliminating this subpopulation of cells would theoretically result in tumor eradication, PaCSCs are extremely plastic and can successfully adapt to targeted therapies. In this study, we demonstrate that PaCSCs increase expression of interferon-stimulated gene 15 (ISG15) and protein ISGylation, which are essential for maintaining their metabolic plasticity. CRISPR-mediated ISG15 genomic editing reduces overall ISGylation, impairing PaCSCs self-renewal and their in vivo tumorigenic capacity. At the molecular level, ISG15 loss results in decreased mitochondrial ISGylation concomitant with increased accumulation of dysfunctional mitochondria, reduced oxidative phosphorylation (OXPHOS) and impaired mitophagy. Importantly, disruption in mitochondrial metabolism affects PaCSC metabolic plasticity, making them susceptible to prolonged inhibition with metformin in vivo. Thus, ISGylation is critical for optimal and efficient OXPHOS by ensuring the recycling of dysfunctional mitochondria, and when absent, a dysregulation in mitophagy occurs that negatively impacts PaCSC stemness

A retrospective, multicenter study of the efficacy of lapatinib plus trastuzumab in HER2-positive metastatic breast cancer patients previously treated with trastuzumab, lapatinib, or both: the Trastyvere study

[Purpose]: To evaluate the efficacy and safety of lapatinib (L) and trastuzumab (T) combination in HER2-positive metastatic breast cancer (MBC) patients previously treated with T and/or L.[Materials and methods]: We conducted a retrospective, post-authorized, multicenter study including patients with HER2-positive MBC or locally advanced breast cancer (ABC) treated with the combination of L–T. Concomitant endocrine therapy, as well as brain metastasis and/or prior exposure to L, were allowed.[Results]: One hundred and fifteen patients from 14 institutions were included. The median age was 59.8 years. The median number of prior T regimens in the advanced setting was 3 and 73 patients had received a prior L regimen. The clinical benefit rate (CBR) was 34.8% (95% CI 26.1–43.5). Among other efficacy endpoints, the overall response rate was 21.7%, and median progression-free survival (PFS) and overall survival were 3.9 and 21.6 months, respectively. Heavily pretreated and ≥ 3 metastatic organ patients showed lower CBR and PFS than patients with a low number of previous regimens and < 3 metastatic organs. Moreover, CBR did not significantly change in L-pretreated compared with L-naïve patients (31.5% versus 40.5% for L-pretreated versus L-naïve). Grade 3/4 adverse events were reported in 19 patients (16.5%).[Conclusion]: The combination of L–T is an effective and well-tolerated regimen in heavily pretreated patients and remains active among patients progressing on prior L-based therapy. Our study suggests that the L–T regimen is a safe and active chemotherapy-free option for MBC patients previously treated with T and/or L.This work was supported by GlaxoSmithKline plc (GSK) through a contract with Medica Scientia Innovation Research (MedSIR), an academic research organization focused on independent clinical research development

Statistical validation of Aeolus L2A particle backscatter coefficient retrievals over ACTRIS/EARLINET stations on the Iberian Peninsula

The Global Observing System (GOS) has encountered some limitations due to a lack of worldwide real-time wind measurements. In this context, the European Space Agency (ESA) has developed the Aeolus satellite mission, based on the ALADIN (Atmospheric Laser Doppler Instrument) Doppler wind lidar; this mission aims to obtain near-real-time wind retrievals at the global scale. As spin-off products, the instrument retrieves aerosol optical properties such as particle backscatter and extinction coefficients. In this work, a validation of Aeolus reprocessed (baseline 10) co-polar backscatter coefficients ( part Aeolus) is presented through an intercomparison with analogous ground-based measurements taken at the ACTRIS (Aerosols, Clouds and Trace gases Research InfraStructure Network)/EARLINET (European Aerosol Research Lidar Network) stations of Granada (Spain), Évora (Portugal) and Barcelona (Spain) over the period from July 2019 until October 2020. Case studies are first presented, followed by a statistical analysis. The stations are located in a hot spot between Africa and the rest of Europe, which guarantees a variety of aerosol types, from mineral dust layers to continental/anthropogenic aerosol, and allows us to test Aeolus performance under different scenarios. The so called Aeolus-like profiles ( part Aeolus like;355) are obtained from total particle backscatter coefficient and linear particle depolarization ratio ( part linear) profiles at 355 and 532 nm measured from the surface, through a thorough bibliographic review of dual-polarization measurements for relevant aerosol types. Finally, the study proposes a relation for the spectral conversion of part linear, which is implemented in the Aeolus-like profile calculation. The statistical results show the ability of the satellite to detect and characterize significant aerosol layers under cloud-free conditions, along with the surface effect on the lowermost measurements, which causes the satellite to largely overestimate copolar backscatter coefficients. Finally, the Aeolus standard correct algorithm middle bin (SCAmb) shows a better agreement with ground-based measurements than the standard correct algorithm (SCA), which tends to retrieve negative and meaningless coefficients in the clear troposphere. The implementation of Aeolus quality flags entails a vast reduction in the number of measurements available for comparison, which affects the statistical significance of the results

Barrier crossings and winds shape daily travel schedules and speeds of a flight generalist

External factors such as geography and weather strongly affect bird migration influencing daily travel schedules and flight speeds. For strictly thermal-soaring migrants, weather explains most seasonal and regional differences in speed. Flight generalists, which alternate between soaring and flapping flight, are expected to be less dependent on weather, and daily travel schedules are likely to be strongly influenced by geography and internal factors such as sex. We GPS-tracked the migration of 70 lesser kestrels (Falco naumanni) to estimate the relative importance of external factors (wind, geography), internal factors (sex) and season, and the extent to which they explain variation in travel speed, distance, and duration. Our results show that geography and tailwind are important factors in explaining variation in daily travel schedules and speeds. We found that wind explained most of the seasonal differences in travel speed. In both seasons, lesser kestrels sprinted across ecological barriers and frequently migrated during the day and night. Conversely, they travelled at a slower pace and mainly during the day over non-barriers. Our results highlighted that external factors far outweighed internal factors and season in explaining variation in migratory behaviour of a flight generalist, despite its ability to switch between flight modes.Peer reviewe

Transcriptomal profiling of the cellular response to DNA damage mediated by Slug (Snai2)

Snai2-deficient cells are radiosensitive to DNA damage. The function of Snai2 in response to DNA damage seems to be critical for its function in normal development and cancer. Here, we applied a functional genomics approach that combined gene-expression profiling and computational molecular network analysis to obtain global dissection of the Snai2-dependent transcriptional response to DNA damage in primary mouse embryonic fibroblasts (MEFs), which undergo p53-dependent growth arrest in response to DNA damage. Although examination of the response showed that overall expression of p53 target gene expression patterns was similarly altered in both control and Snai2-deficient cells, we have identified and validated candidate Snai2 target genes linked to Snai2 gene function in response to DNA damage. This work defines for the first time the effect of Snai2 on p53 target genes in cells undergoing growth arrest, elucidates the Snai2-dependent molecular network induced by DNA damage, points to novel putative Snai2 targets, and suggest a mechanistic model, which has implications for cancer management

Unraveling the effect of silent, intronic and missense mutations on VWF splicing: contribution of next generation sequencing in the study of mRNA

Large studies in von Willebrand disease patients, including Spanish and Portuguese registries, led to identification of >250 different mutations. It is a challenge to determine the pathogenic effect of potential splice site mutations on VWF mRNA. This study aimed to elucidate the true effects of 18 mutations on VWF mRNA processing, investigate the contribution of next-generation sequencing to in vivo mRNA study in von Willebrand disease, and compare the findings with in silico prediction. RNA extracted from patient platelets and leukocytes was amplified by RT-PCR and sequenced using Sanger and next generation sequencing techniques. Eight mutations affected VWF splicing: c.1533+1G>A, c.5664+2T>C and c.546G>A (p.=) prompted exon skipping; c.3223-7_3236dup and c.7082-2A>G resulted in activation of cryptic sites; c.3379+1G>A and c.7473G>A (p.=) demonstrated both molecular pathogenic mechanisms simultaneously; and the p.Cys370Tyr missense mutation generated two aberrant transcripts. Of note, the complete effect of 3 mutations was provided by next generation sequencing alone because of low expression of the aberrant transcripts. In the remaining 10 mutations, no effect was elucidated in the experiments. However, the differential findings obtained in platelets and leukocytes provided substantial evidence that 4 of these would have an effect on VWF levels. In this first report using next generation sequencing technology to unravel the effects of VWF mutations on splicing, the technique yielded valuable information. Our data bring to light the importance of studying the effect of synonymous and missense mutations on VWF splicing to improve the current knowledge of the molecular mechanisms behind von Willebrand disease.info:eu-repo/semantics/publishedVersio