Modern Acinetobacter baumannii clinical isolates replicate inside spacious vacuoles and egress from macrophages

Multidrug-resistant Acinetobacter baumannii infections are increasing at alarming rates. Therefore, novel antibiotic-sparing treatments to combat these A. baumannii infections are urgently needed. The development of these interventions would benefit from a better understanding of this bacterium\u27s pathobiology, which remains poorly understood. A. baumannii is regarded as an extracellular opportunistic pathogen. However, research on Acinetobacter has largely focused on common lab strains, such as ATCC 19606, that have been isolated several decades ago. These strains exhibit reduced virulence when compared to recently isolated clinical strains. In this work, we demonstrate that, unlike ATCC 19606, several modern A. baumannii clinical isolates, including the recent clinical urinary isolate UPAB1, persist and replicate inside macrophages within spacious vacuoles. We show that intracellular replication of UPAB1 is dependent on a functional type I secretion system (T1SS) and pAB5, a large conjugative plasmid that controls the expression of several chromosomally-encoded genes. Finally, we show that UPAB1 escapes from the infected macrophages by a lytic process. To our knowledge, this is the first report of intracellular growth and replication of A. baumannii. We suggest that intracellular replication within macrophages may contribute to evasion of the immune response, dissemination, and antibiotic tolerance of A. baumannii

Factors related to survival in Intensive Care Unit patients with Covid-19: a study from a single center in Brazil

Introduction: Analysis of the outcome of 268 ICU patients in a single-center, as well the impact of viral infection on patients with preexisting medical conditions and how these factors affected survival and hospital stay. Methodology: Patients admitted to the ICU from March-August, 2020 were retrospectively analyzed under the same protocol at Hospital Alemão Oswaldo Cruz, São Paulo, Brazil. Several factors were considered and the results were presented using 95% confidence intervals. For statistical significance, p <0.05 was adopted. Results: Patient median age was 72 years, 64,2 years for discharged patients and 79.9 years for those deceased (p<0.001). The most common comorbidities were: systemic arterial hypertension, diabetes, thyroid disease, cardiovascular and kidney disease. Predictors of survival through univariate analysis: myalgia (p=0.001), cerebrovascular disease (p=0.002), COPD (p=0.003), dementia (p=0.000), mechanical ventilation (p=0.000), dialysis (0.000), vasopressor use (0.000), SAPS3 (0.000), lymphopenia (p=0.004), elevated D-dimer (P=0.011), time in ICU before tracheostomy (p=0.002), and performing a tracheostomy (p=0.000). The independent predictors of mortality were: advanced age (p=0.003) and tracheostomy performed in ICU (p=0.002). Discussion: COVID-19 affects usually older adults, where there already is a higher fatality rate. Acute respiratory distress syndrome is the primary cause of death and <5% of patients were reported as experiencing co-infection at admission. Conclusion: age, vasopressor use in patients with tracheostomy, and systemic coronary disease, heart failure, neoplasia, and COPD, were found to be significantly associated with COVID-19 severity

Long-term impact of a conditional cash transfer programme on maternal mortality: a nationwide analysis of Brazilian longitudinal data.

BACKGROUND: Reducing poverty and improving access to health care are two of the most effective actions to decrease maternal mortality, and conditional cash transfer (CCT) programmes act on both. The aim of this study was to evaluate the effects of one of the world's largest CCT (the Brazilian Bolsa Familia Programme (BFP)) on maternal mortality during a period of 11 years. METHODS: The study had an ecological longitudinal design and used all 2548 Brazilian municipalities with vital statistics of adequate quality during 2004-2014. BFP municipal coverage was classified into four levels, from low to consolidated, and its duration effects were measured using the average municipal coverage of previous years. We used negative binomial multivariable regression models with fixed-effects specifications, adjusted for all relevant demographic, socioeconomic, and healthcare variables. RESULTS: BFP was significantly associated with reductions of maternal mortality proportionally to its levels of coverage and years of implementation, with a rate ratio (RR) reaching 0.88 (95%CI 0.81-0.95), 0.84 (0.75-0.96) and 0.83 (0.71-0.99) for intermediate, high and consolidated BFP coverage over the previous 11 years. The BFP duration effect was stronger among young mothers (RR 0.77; 95%CI 0.67-0.96). BFP was also associated with reductions in the proportion of pregnant women with no prenatal visits (RR 0.73; 95%CI 0.69-0.77), reductions in hospital case-fatality rate for delivery (RR 0.78; 95%CI 0.66-0.94) and increases in the proportion of deliveries in hospital (RR 1.05; 95%CI 1.04-1.07). CONCLUSION: Our findings show that a consolidated and durable CCT coverage could decrease maternal mortality, and these long-term effects are stronger among poor mothers exposed to CCT during their childhood and adolescence, suggesting a CCT inter-generational effect. Sustained CCT coverage could reduce health inequalities and contribute to the achievement of the Sustainable Development Goal 3.1, and should be preserved during the current global economic crisis due to the COVID-19 pandemic

The Development of Linguistic Competences for Employability: A Training Project for Teachers

AbstractEmployability is a new concept that has just appeared in the Spanish educational system. Its rising importance is due to European Union educational policies which aim to provide young people with training that enables them to take part successfully in the present and future working world.This paper argues for the need to develop employability from the very start of formal education, and within this, we highlight the importance of developing linguistic competence among pre-school and primary pupils as a key element for favouring employability.To be able to do so, the teaching staff must be trained using quality education to enable them to work effectively on this competence. In this paper we present how a training program, with a specific European dimension, has been designed by a state school from the Valencian Community, to serve as a model for other schools concerned about the development of a linguistic competence that helps to improve both teachers’ and pupils’ employability

Herbicidas alachlor, pendimethalin e trifluralin na nodulação e crescimento inicial de plantas de amendoim

This work had the objective of evaluating the effect of the herbicides alachlor, pendimethalin and trifluralin on the initial growth of peanut plants (Arachis hypogaea L.) under greenhouse conditions for a period of thirty days as well as nodule number and dry weight for sixty days after the sowing period. The experiment was conducted at the Agronomy College of the Federal University ofBahia.The first experimental design was completely randomized with four treatments (control- rate zero; alachlor - 2.90 kg/ha, pendimethalin - 1.00 kg/haand trifluralin - 0.89 kg/ha) and three replieations. For each replication, plastie trays (70 em x 50 em x 10 em) were used with a yellow Latosol as the substrate and peanut seeds of the variety BRS 151-L 7 provided by EMBRAPA-CNPA. A seeond experiment was condueted with plastic pots of 5 kg, the same substrate, same treatments and experimental design with eight replieations. The following parameters were evaluated: seedling emergence, percentage of abnonnal seedlings and dead seeds, plant height, index of seedling emergenee velocity, root and shoot dry weight,number and dry weight of nodules. The results show that herbieides stimulate the initial nodulation of peanut plants, but reduce the pereentage of emergence, shoot dry weight and plant height. Therefore, the herbicides should be recommended with restrietions, for the studied eonditions. . Este trabalho teve como objetivos avaliar o efeito dos herbicidas alachlor, pendimethalin e trifluralin no crescimento inicial de plantas de amendoim (Arachis hypogaea L.) em casa de vegetação, por um período de trinta dias, e o número e massa seca dos nódulos após 60 dias do plantio. O experimento foi conduzido na casa de vegetação do Departamento de Química Agrícola e Solos da Escola de Agronomia da Uni versidade Federal da Bahia. O delineamento experimental do primeiro ensaio foi inteiramente casualizado, com quatro tratamentos e três repetições. Os tratamentos utilizados foram: alachlor (2,90 kg ha); pendimethalin (1,00 kg ha), trifluralin (0,89 kg ha) e testemunha. As parcelas foram constituidas de bandejas de plástico de 70 em x 50 em x 10 em, tendo como substrato um solo Latossolo amarelo álico coeso, utilizando-se sementes da variedade BRS 151- L7, oriundas da EMBRAPAlCNPA. No segundo ensaio, a unidade experimental constituiu-se de vasos plásticos de 5 kg com os mesmos tratamentos, substrato e delineamento experimental, com oito repetições. Avaliou-se os seguintes parâmetros: percentagem de emergência, plântulas anormais, sementes mortas, altura da planta, comprimento da raiz, índice de velocidade de emergência, massa seca da parte aérea e da raiz, número e massa seca de nódulos. Os herbicidas testados, apesar de estimularem a nodulação inicial das plantas de amendoim, reduzem a porcentagem de emergência, massa seca da parte aérea e altura das plantas, devendo ser recomendados com restrições nas condições estudadas.

Tumour compartment transcriptomics demonstrates the activation of inflammatory and odontogenic programmes in human adamantinomatous craniopharyngioma and identifies the MAPK/ERK pathway as a novel therapeutic target

Adamantinomatous craniopharyngiomas (ACPs) are clinically challenging tumours, the majority of which have activating mutations in CTNNB1. They are histologically complex, showing cystic and solid components, the latter comprised of different morphological cell types (e.g. β-catenin-accumulating cluster cells and palisading epithelium), surrounded by a florid glial reaction with immune cells. Here, we have carried out RNA sequencing on 18 ACP samples and integrated these data with an existing ACP transcriptomic dataset. No studies so far have examined the patterns of gene expression within the different cellular compartments of the tumour. To achieve this goal, we have combined laser capture microdissection with computational analyses to reveal groups of genes that are associated with either epithelial tumour cells (clusters and palisading epithelium), glial tissue or immune infiltrate. We use these human ACP molecular signatures and RNA-Seq data from two ACP mouse models to reveal that cell clusters are molecularly analogous to the enamel knot, a critical signalling centre controlling normal tooth morphogenesis. Supporting this finding, we show that human cluster cells express high levels of several members of the FGF, TGFB and BMP families of secreted factors, which signal to neighbouring cells as evidenced by immunostaining against the phosphorylated proteins pERK1/2, pSMAD3 and pSMAD1/5/9 in both human and mouse ACP. We reveal that inhibiting the MAPK/ERK pathway with trametinib, a clinically approved MEK inhibitor, results in reduced proliferation and increased apoptosis in explant cultures of human and mouse ACP. Finally, we analyse a prominent molecular signature in the glial reactive tissue to characterise the inflammatory microenvironment and uncover the activation of inflammasomes in human ACP. We validate these results by immunostaining against immune cell markers, cytokine ELISA and proteome analysis in both solid tumour and cystic fluid from ACP patients. Our data support a new molecular paradigm for understanding ACP tumorigenesis as an aberrant mimic of natural tooth development and opens new therapeutic opportunities by revealing the activation of the MAPK/ERK and inflammasome pathways in human ACP. KEYWORDS: Craniopharyngioma; IL1-β; Inflammasome; MAPK/ERK pathway; Odontogenesis; Paracrine signalling; Trametini

Genomics and epidemiology for gastric adenocarcinomas (GE4GAC): a Brazilian initiative to study gastric cancer

Abstract Gastric cancer (GC) is the fifth most common type of cancer worldwide with high incidences in Asia, Central, and South American countries. This patchy distribution means that GC studies are neglected by large research centers from developed countries. The need for further understanding of this complex disease, including the local importance of epidemiological factors and the rich ancestral admixture found in Brazil, stimulated the implementation of the GE4GAC project. GE4GAC aims to embrace epidemiological, clinical, molecular and microbiological data from Brazilian controls and patients with malignant and pre-malignant gastric disease. In this letter, we summarize the main goals of the project, including subject and sample accrual and current findings

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the Extended Baryon Oscillation Spectroscopic Survey and from the Second Phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014–2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population