A importância dos meios de comunicação na promoção do direito à educação e à informação

O direito à educação e à informação são direitos fundamentais em democracia. Saber se os direito à educação e à informação e ao conhecimento se concretizam pela consagração constitucional do direito à educação e como é possível encontrá-lo consagrado, quer ao nível do direito interno dos Estados quer ao nível do direito da União Europeia é hoje da maior pertinência, com os direitos fundamentais na agenda política. O objetivo desta análise é demonstrar que o papel da comunicação social é crucial, e que a UE promove ativamente a educação, investigação e inovação. Estas são as vias para promover o desenvolvimento com base no crescimento do emprego e da coesão social. Os meios de comunicação social podem dar um contributo fundamental para enfrentar problemas importantes ligados ao crescimento económico e este vector vem mesmo consagrado no âmbito da estratégia global do programa Europa 2020. Na dimensão nacional portuguesa, o direito à educação e informação é apresentado como um direito cultural da Constituição. Já no direito de vertente europeia, o direito à educação surge em protocolo da Convenção Europeia dos Direitos do Homem de 1950 e é consagrado na Carta dos Direitos Fundamentais da União Europeia. Em qualquer dos casos há uma dimensão positiva neste direito que envolve a intervenção dos Estados, e os meios de comunicação social podem ter um papel relevante neste âmbito. Atendendo aos pressupostos e objetivos delineados acima, e considerando a natureza embrionária deste estudo, foi desenhada uma metodologia que aborda a revisão da literatura sobre os vários temas abordados, com especial enfoque na questão da educação e informação. Dedutivamente, será assim possível inferir o contributo do direito interno e europeu bem como da comunicação social para a concretização deste desiderato. O estado da arte, de pendor teórico-académico, será consolidado através da interpretação normativa sistemática e metodologicamente selecionada dos textos legais e de textos informativos emanados pelos meios de comunicação

Cross-Linking Mass Spectrometry Uncovers Interactions Between High-Density Lipoproteins and the SARS-CoV-2 Spike Glycoprotein

High-density lipoprotein (HDL) levels are reduced in patients with coronavirus disease 2019 (COVID-19), and the extent of this reduction is associated with poor clinical outcomes. While lipoproteins are known to play a key role during the life cycle of the hepatitis C virus, their influence on coronavirus (CoV) infections is poorly understood. In this study, we utilize cross-linking mass spectrometry (XL-MS) to determine circulating protein interactors of the severe acute respiratory syndrome (SARS)-CoV-2 spike glycoprotein. XL-MS of plasma isolated from patients with COVID-19 uncovered HDL protein interaction networks, dominated by acute-phase serum amyloid proteins, whereby serum amyloid A2 was shown to bind to apolipoprotein (Apo) D. XL-MS on isolated HDL confirmed ApoD to interact with SARS-CoV-2 spike but not SARS-CoV-1 spike. Other direct interactions of SARS-CoV-2 spike upon HDL included ApoA1 and ApoC3. The interaction between ApoD and spike was further validated in cells using immunoprecipitation-MS, which uncovered a novel interaction between both ApoD and spike with membrane-associated progesterone receptor component 1. Mechanistically, XL-MS coupled with data-driven structural modeling determined that ApoD may interact within the receptor-binding domain of the spike. However, ApoD overexpression in multiple cell-based assays had no effect upon viral replication or infectivity. Thus, SARS-CoV-2 spike can bind to apolipoproteins on HDL, but these interactions do not appear to alter infectivity.</p

Anticontractile Effect of Perivascular Adipose Tissue and Leptin are Reduced in Hypertension

Leptin causes vasodilatation both by endothelium-dependent and -independent mechanisms. Leptin is synthesized by perivascular adipose tissue (PVAT). The hypothesis of this study is that a decrease of leptin production in PVAT of spontaneously hypertensive rats (SHR) might contribute to a diminished paracrine anticontractile effect of the hormone. We have determined in aorta from Wistar-Kyoto (WKY) and SHR (i) leptin mRNA and protein levels in PVAT, (ii) the effect of leptin and PVAT on contractile responses, and (iii) leptin-induced relaxation and nitric oxide (NO) production. Leptin mRNA and protein expression were significantly lower in PVAT from SHR. Concentration-response curves to angiotensin II were significantly blunted in presence of PVAT as well as by exogenous leptin (10−9 M) only in WKY. This anticontractile effect was endothelium-dependent. Vasodilatation induced by leptin was smaller in SHR than in WKY, and was also endothelium-dependent. Moreover, release of endothelial NO in response to acute leptin was higher in WKY compared to SHR, but completely abolished in the absence of endothelium. In conclusion, the reduced anticontractile effect of PVAT in SHR might be attributed to a reduced PVAT-derived leptin and to an abrogated effect of leptin on endothelial NO release probably due to an impaired activation of endothelial NO synthase

Pluripotent Stem Cell-Derived Hepatocytes Inhibit T Cell Proliferation In Vitro through Tryptophan Starvation.

Regenerative medicine aims to replace damaged tissues by stimulating endogenous tissue repair or by transplanting autologous or allogeneic cells. Due to their capacity to produce unlimited numbers of cells of a given cell type, pluripotent stem cells, whether of embryonic origin or induced via the reprogramming of somatic cells, are of considerable therapeutic interest in the regenerative medicine field. However, regardless of the cell type, host immune responses present a barrier to success. The aim of this study was to investigate in vitro the immunological properties of human pluripotent stem cell (PSC)-derived hepatocyte-like cells (HLCs). These cells expressed MHC class I molecules while they lacked MHC class II and co-stimulatory molecules, such as CD80 and CD86. Following stimulation with IFN-γ, HLCs upregulated CD40, PD-L1 and MHC class I molecules. When co-cultured with allogeneic T cells, HLCs did not induce T cell proliferation; furthermore, when T cells were stimulated via αCD3/CD28 beads, HLCs inhibited their proliferation via IDO1 and tryptophan deprivation. These results demonstrate that PSC-derived HLCs possess immunoregulatory functions, at least in vitro

Kinetics of early innate immune activation during HIV-1 infection of humanized mice

Human immunodeficiency virus type-1 (HIV-1) infection is associated with aberrant immune activation, however, most model systems for HIV-1 have been used during established infection. Here, we utilize ultra-sensitive HIV-1 quantification to delineate early events during the HIV-1 eclipse, burst and chronic phases of HIV-1 infection in humanized mice. We show that very early in infection, HIV-1 suppresses peripheral type I interferon (IFN) and interferon-stimulated gene (ISG) responses, including the HIV-1 restriction factor IFI44. At the peak of innate immune activation, prior to CD4 T cell loss, HIV-1 infection differentially affects peripheral and lymphoid TLR expression profiles in T cells and macrophages. This results in a trend towards an altered activation of NFκB, TBK1 and IRF3. The subsequent type I and III IFN responses result in preferential induction of peripheral ISG responses. Following this initial innate immune activation, peripheral expression of the HIV-1 restriction factor SAMHD1 returns to levels below those observed in uninfected mice, suggesting that HIV-1 interferes with their basal expression. However, peripheral cells, still retain their responsiveness to exogenous type I IFN, whereas splenic cells show a reduction in select ISG in response to IFN. This demonstrates the highly dynamic nature of very early HIV-1 infection and suggests that blocks to the induction of HIV-1 restriction factors contribute to the establishment of viral persistence.IMPORTANCE Human immunodeficiency virus (HIV)-1 infection is restricted to humans and some non-human primates (e.g. chimpanzee, gorilla). Alternative model systems based on SIV infection of macaques are available but do not recapitulate all aspects of HIV-1 infection and disease. Humanized mice, which contain a human immune system, can be used to study HIV-1 but only limited information on early events and immune responses are available to date. Here, we describe very early immune responses to HIV-1 and demonstrate a suppression of cell-intrinsic innate immunity. Furthermore, we show that HIV-1 infection interacts differently with innate immune responses in blood and lymphoid organs

Identification of Broad-Spectrum Antiviral Compounds by Targeting Viral Entry.

Viruses are a major threat to human health and economic well-being. In recent years Ebola, Zika, influenza, and chikungunya virus epidemics have raised awareness that infections can spread rapidly before vaccines or specific antagonists can be made available. Broad-spectrum antivirals are drugs with the potential to inhibit infection by viruses from different groups or families, which may be deployed during outbreaks when specific diagnostics, vaccines or directly acting antivirals are not available. While pathogen-directed approaches are generally effective against a few closely related viruses, targeting cellular pathways used by multiple viral agents can have broad-spectrum efficacy. Virus entry, particularly clathrin-mediated endocytosis, constitutes an attractive target as it is used by many viruses. Using a phenotypic screening strategy where the inhibitory activity of small molecules was sequentially tested against different viruses, we identified 12 compounds with broad-spectrum activity, and found a subset blocking viral internalisation and/or fusion. Importantly, we show that compounds identified with this approach can reduce viral replication in a mouse model of Zika infection. This work provides proof of concept that it is possible to identify broad-spectrum inhibitors by iterative phenotypic screenings, and that inhibition of host-pathways critical for viral life cycles can be an effective antiviral strategy

Estudio de factores predictivos de respuesta patológica a quimioterapia neoadyuvante en el cáncer de mama receptores hormonales positivos HER2 negativo

Se trata de un estudio de casos de carcinomas de mama con escasa información respecto a los factores que determinan la repuesta a quimioterapia neoadyuvante. Un elevado nivel de proliferación y el estado de receptores hormonales han mostrado ser predictivos de dicha respuesta.La quimioterapia neoadyuvante (QTN) se utiliza cada vez más para conseguir una reducción tumoral que permita una cirugía conservadora y, mediante el grado de respuesta patológica tumoral, determinar el pronóstico de las pacientes. Los datos anatomopatológicos proporcionados por la biopsia previa al tratamiento (BAG), podrían ser determinantes para conocer el grado de respuesta y estar relacionados con la evolución de la enfermedad. El objetivo del estudio es, determinar el valor predictivo de respuesta, basado en variables anatomopatológicas de la BAG, en una cohorte de 220 casos de mujeres con cáncer de mama fenotipo RE positivo y HER2 negativo, tratadas de 3 a 6 meses con antraciclina/taxanos, en 4 hospitales de Andalucía, desde el año 2003 al año 2014. El tamaño previo tumoral, el grado histológico, RE (receptores de estrógenos), RP (receptores de progesterona), nivel de proliferación (Ki67) y subtipo molecular subrrogado inmunohistoquímico, fueron evaluados en la BAG, y se compararon con el grado de respuesta a QTN en la pieza quirúrgica (sistemas de Miller y Payne [MyP] y RCB) valorado por un observador. Resultados: En nuestro estudio, los tumores con inmunoexpresión de RE 50% (p<0,05). Además, responden mejor al tratamiento los carcinoma con subtipo luminal B que los luminal A (p=0,04). Conclusiones: Además de un elevado nivel de proliferación, el estado de receptores de estrógenos y progesterona también influye en la respuesta a QTN en carcinoma de mama Her2 negativo, respondiendo mejor los pacientes con expresión hormonal baja. Probablemente relacionado con lo anterior, las pacientes con subtipo luminal B, mostratron una mejor respuesta.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study

Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide