Head-to-head antisense transcription and R-loop formation promotes transcriptional activation

The mechanisms used by antisense transcripts to regulate their corresponding sense mRNAs are not fully understood. Herein, we have addressed this issue for the vimentin (VIM) gene, a member of the intermediate filament family involved in cell and tissue integrity that is deregulated in different types of cancer. VIM mRNA levels are positively correlated with the expression of a previously uncharacterized head-to-head antisense transcript, both transcripts being silenced in colon primary tumors concomitant with promoter hypermethylation. Furthermore, antisense transcription promotes formation of an R-loop structure that can be disfavored in vitro and in vivo by ribonuclease H1 overexpression, resulting in VIM down-regulation. Antisense knockdown and R-loop destabilization both result in chromatin compaction around the VIM promoter and a reduction in the binding of transcriptional activators of the NF-κB pathway. These results are the first examples to our knowledge of R-loop–mediated enhancement of gene expression involving head-to-head antisense transcription at a cancer-related locus

Immune senescence and cancer in elderly patients: Results from an exploratory study

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Failures of 13-Valent Conjugated Pneumococcal Vaccine in Age-Appropriately Vaccinated Children 2-59 Months of Age, Spain

Vaccination with the 13-valent conjugated pneumococcal disease (PCV13) has reduced invasive pneumococcal disease (IPD), but there have been reports of vaccine failures. We performed a prospective study in children aged 2-59 months who received diagnoses of IPD during January 2012-June 2016 in 3 pediatric hospitals in Catalonia, Spain, a region with a PCV13 vaccination coverage of 63%. We analyzed patients who had been age-appropriately vaccinated but who developed IPD caused by PCV13 serotypes. We detected 24 vaccine failure cases. The serotypes involved were 3 (16 cases); 19A (5 cases); and 1, 6B, and 14 (1 case each). Cases were associated with children without underlying conditions, with complicated pneumonia (OR 6.65, 95% CI 1.91-23.21), and with diagnosis by PCR (OR 5.18, 95% CI 1.84-14.59). Vaccination coverage should be increased to reduce the circulation of vaccine serotypes. Continuous surveillance of cases of IPD using both culture and PCR to characterize vaccine failures is necessary

Interplay between COVID-19, pollution, and weather features on changes in the incidence of acute coronary syndromes in early 2020

Coronavirus disease 2019 (COVID-19) has caused an unprecedented change in the apparent epidemiology of acute coronary syndromes (ACS). However, the interplay between this disease, changes in pollution, climate, and aversion to activation of emergency medical services represents a challenging conundrum. We aimed at appraising the impact of COVID-19, weather, and environment features on the occurrence of ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) in a large Italian region and metropolitan area

Multiplex RNA-based detection of clinically relevant MET alterations in advanced non-small cell lung cancer

We studied MET alterations in 474 advanced non-small-cell lung cancer (NSCLC) patients by nCounter, an RNA-based technique. We identified 3% with MET Δex14 mRNA and 3.5% with very-high MET mRNA expression, a surrogate of MET amplification. MET alterations identified by nCounter correlated with clinical benefit from MET inhibitors. Quantitative mRNA-based techniques can improve the selection of patients for MET-targeted therapies. MET inhibitors have shown activity in non-small-cell lung cancer patients (NSCLC) with MET amplification and exon 14 skipping (METΔex14). However, patient stratification is imperfect, and thus, response rates have varied widely. Here, we studied MET alterations in 474 advanced NSCLC patients by nCounter, an RNA-based technique, together with next-generation sequencing (NGS), fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and reverse transcriptase polymerase chain reaction (RT-PCR), exploring correlation with clinical benefit. Of the 474 samples analyzed, 422 (89%) yielded valid results by nCounter, which identified 13 patients (3%) with MET Δex14 and 15 patients (3.5%) with very-high MET mRNA expression. These two subgroups were mutually exclusive, displayed distinct phenotypes and did not generally coexist with other drivers. For MET Δex14, 3/8 (37.5%) samples positive by nCounter tested negative by NGS. Regarding patients with very-high MET mRNA, 92% had MET amplification by FISH and/or NGS. However, FISH failed to identify three patients (30%) with very-high MET RNA expression, among which one received MET tyrosine kinase inhibitor treatment deriving clinical benefit. Our results indicate that quantitative mRNA-based techniques can improve the selection of patients for MET-targeted therapies

Gal-1 Expression Analysis in the GLIOCAT Multicenter Study: Role as a Prognostic Factor and an Immune-Suppressive Biomarker

Glioblastoma (GBM) is the most frequent primary malignant brain tumor and has a dismal prognosis. Unfortunately, despite the recent revolution of immune checkpoint inhibitors in many solid tumors, these have not shown a benefit in overall survival in GBM patients. Therefore, new potential treatment targets as well as diagnostic, prognostic, and/or predictive biomarkers are needed to improve outcomes in this population. The beta-galactoside binding protein Galectin-1 (Gal-1) is a protein with a wide range of pro-tumor functions such as proliferation, invasion, angiogenesis, and immune suppression. Here, we evaluated Gal-1 expression by immunohistochemistry in a homogenously treated cohort of GBM (the GLIOCAT project) and correlated its expression with clinical and molecular data. We observed that Gal-1 is a negative prognostic factor in GBM. Interestingly, we observed higher levels of Gal-1 expression in the mesenchymal/classical subtypes compared to the less aggressive proneural subtype. We also observed a Gal-1 expression correlation with immune suppressive signatures of CD4 T-cells and macrophages, as well as with several GBM established biomarkers, including SHC1, PD-L1, PAX2, MEOX2, YKL-40, TCIRG1, YWHAG, OLIG2, SOX2, Ki-67, and SOX11. Moreover, Gal-1 levels were significantly lower in grade 4 IDH-1 mutant astrocytomas, which have a better prognosis. Our results confirm the role of Gal-1 as a prognostic factor and also suggest its value as an immune-suppressive biomarker in GBM

Effectiveness of the 13-valent pneumococcal conjugate vaccine in preventing invasive pneumococcal disease in children aged 7-59 months. A matched case-control study

Background The 13-valent pneumococcal conjugate vaccine (PCV13) was licensed based on the results of immunogenicity studies and correlates of protection derived from randomized clinical trials of the 7-valent conjugate pneumococcal vaccine. We assessed the vaccination effectiveness (VE) of the PCV13 in preventing invasive pneumococcal disease (IPD) in children aged 7-59 months in a population with suboptimal vaccination coverage of 55%. Methods The study was carried out in children with IPD admitted to three hospitals in Barcelona (Spain) and controls matched by hospital, age, sex, date of hospitalization and underlying disease. Information on the vaccination status was obtained from written medical records. Conditional logistic regression was made to estimate the adjusted VE and 95% confidence intervals (CI). Results 169 cases and 645 controls were included. The overall VE of ≥1 doses of PCV13 in preventing IPD due to vaccine serotypes was 75.8% (95% CI, 54.1-87.2) and 90% (95% CI, 63.9-97.2) when ≥2 doses before 12 months, two doses on or after 12 months or one dose on or after 24 months, were administered. The VE of ≥1 doses was 89% (95% CI, 42.7-97.9) against serotype 1 and 86.0% (95% CI, 51.2-99.7) against serotype 19A. Serotype 3 showed a non-statistically significant effectiveness (25.9%; 95% CI, -65.3 to 66.8). Conclusions The effectiveness of ≥1 doses of PCV13 in preventing IPD caused by all PCV13 serotypes in children aged 7-59 months was good and, except for serotype 3, the effectiveness of ≥1 doses against the most frequent PCV13 serotypes causing IPD was high when considered individually

Impact of the 13-valent conjugated pneumococcal vaccine on the direct costs of invasive pneumococcal disease requiring hospital admission in children aged < 5 years. A prospective study

The lack of invasive pneumococcal disease (IPD) cost studies may underestimate the effect of pneumococcal polysaccharide conjugated vaccines (PCV). The objective of this study was to estimate the direct costs of hospitalized IPD cases. A prospective study was made in children aged <5 years diagnosed with IPD in two high-tech hospitals in Catalonia (Spain) between 2007-2009 (PCV7 period) and 2012-2015 (PCV13 period). Costs were calculated according to 2014 Catalan Health Service rates using diagnostic-related groups. In total, 319 and 154 cases were collected, respectively. Pneumonia had the highest cost (65.7% and 62.0%, respectively), followed by meningitis (25.8% and 26.1%, respectively). During 2007-2015, the costs associated with PCV7 serotypes (Pearson coeffcient (Pc) = 0.79; p = 0.036) and additional PCV13 serotypes (Pc = 0.75; p = 0.05) decreased, but those of other serotypes did not (Pc = 0.23 p = 0.62). The total mean cost of IPD increased in the PCV13 period by 31.4% (¿3016.1 vs. ¿3963.9), mainly due to ICU stay (77.4%; ¿1051.4 vs. ¿1865.6). During the PCV13 period, direct IPD costs decreased due to a reduction in the number of cases, but cases were more severe and had a higher mean cost. During 2015, IPD costs increased due to an increase in the costs associated with non-PCV13 serotypes and serotype 3 and this requires further investigation

Island-like mountain radiations in Asia: The case study of the genera Saussurea and Jurinea

Trabajo presentado en el XIX International Botanical Congress (IBC 2017), celebrado en Shenzhen (China) del 23 al 29 de julio de 2017Evolutionary radiations represent events in which many species or lineages evolved from a common ancestor in a short period of time. Many plant radiations have been triggered by island-like ecological opportunities following mountain uplift; the mountain ranges with the steepest and widest environmental gradients, such as the Andes, are home of exceptional regional species pools (and also exceptional endemism rates), mainly derived from evolutionary radiations. The Himalayan-Qinghai-Tibetan Plateau (HQTP) and the adjacent Hengduan Mountains (HM) are considered one of the main biodiversity hotspots of the world thanks to its richness in species and endemics. Both regions show extreme altitudinal ranges compressed in short distances as a consequence of the collision of the Indian and Eurasian plates, and thus constitute ideal evolutionary scenarios to study diversification processes in mountain regions. We have identified two possible cases of alpine radiations in the Saussurea-Jurinea complex (Compositae-Cardueae), involving some 550 species in total. Saussurea shows an amazing number of species (more than 300) in the HQTP and Hengduan mountains, although a considerable number of species are also found on the west side of the mountains of Middle Asia (Tian Shan and Pamir-Alay). Jurinea, in contrast, has the highest number of species (150 sp.) in the Tian Shan and Pamir-Alay. Our general objectives are the following: a) To carry out an extensive sampling of Saussurea and Jurinea, especially centred in the two main radiation areas in the HQTP and Tian Shan mountains; b) To generate well-resolved phylogenies of both genera using a multi-loci approach through next-generation-sequencing (NGS) analyzed by Bayesian inference and parsimony, and explore coalescent-based species tree estimation with our NGS data set; c) On the basis of the new phylogenies, conduct phylogenetic comparative analyses and multi-model biogeographical inference to address the following questions: Do the alpine species of both genera in Asian mountains constitute clades with clearly higher rates of diversification than their lowland relatives? How many independent radiations took place in the complex? If several, did they occur at the same period, and are they comparable in terms of speciation rates? Which factors (intrinsic or extrinsic) shape species radiations, i.e., do the radiations follow a geographical model, an adaptive model, or a mixed model? Our results will be a major contribution to the study of alpine radiations especially in the HQTP, and will open a methodological pathway for the analysis of very large radiations in other genera.Peer reviewe

Pla estratègic d’atenció pal·liativa especialitzada de Catalunya: bases del model de futur

Pla estratègic; Atenció pal·liativa; Atenció centrada en la personaPlan estratégico; Atención paliativa; Atención centrada en la personaStrategic plan; Palliative care; Person centered careAquest Pla estratègic aborda la planificació estratègica de l’atenció a les persones amb necessitats pal·liatives per part dels equips i dispositius de cures pal·liatives específics (a partir d’ara, atenció pal·liativa especialitzada), mentre que de forma conjunta amb la direcció estratègica d’atenció primària i comunitària serà necessari el replantejament de l’atenció al final de vida de forma transversal