Glioblastoma cells: A heterogeneous and fatal tumor interacting with the parenchyma

AbstractGlioblastomas (GBMs) are considered to be one of the deadliest human cancers, characterized by a high proliferative rate, aggressive invasiveness and insensitivity to radio- and chemotherapy, as well as a short patient survival period. Moreover, GBMs are among the most vascularized and invasive cancers in humans. Angiogenesis in GBMs is correlated with the grade of malignancy and is inversely correlated with patient survival. One of the first steps in tumor invasions is migration. GBM cells have the ability to infiltrate and disrupt physical barriers such as basement membranes, extracellular matrix and cell junctions. The invasion process includes the overexpression of several members of a super-family of zinc-based proteinases, the Metzincin, in particular a sub-group, metalloproteinases. Another interesting aspect is that, inside the GBM tissue, there are up to 30% of microglia or macrophages. However, little is known about the immune performance and interactions of the microglia with GBMs. These singular properties of GBMs will be described here. A sub-population of cells with stem-like properties may be the source of tumors since, apparently, GBM stem cells (GSCs) are highly resistant to current cancer treatments. These cancer therapies, while killing the majority of tumor cells, ultimately fail in GBM treatment because they do not eliminate GSCs, which survive to regenerate new tumors. Finally, GBM patient prognostic has shown little improvement in decades. In this context, we will discuss how the membrane-acting toxins called cytolysins can be a potential new tool for GBM treatment

Associação entre distresse moral e elementos apoiadores da deliberação moral em enfermeiros

Objetivo: identificar a associação entre o distresse moral e os elementos apoiadores da deliberação moral em enfermeiros brasileiros. Método: estudo transversal realizado com enfermeiros brasileiros atuantes em serviços de saúde de diferentes níveis de complexidade. O protocolo de pesquisa constituiu-se da Escala Brasileira de Distresse Moral em Enfermeiros, questionário sociodemográfico e laboral, e uma lista de bases e elementos éticos utilizados para deliberação moral. Para análise empregou-se estatística descritiva, teste do qui-quadrado e regressão de Poisson. Resultados: participaram do estudo 1.226 enfermeiros. Os 12 elementos associados ao processo de deliberação moral foram classificados com importância para atuação dos enfermeiros, destacando-se a experiência profissional adquirida, Código de Ética/Lei do Exercício profissional, e, princípios éticos e bioéticos. A relação do distresse moral evidenciou maiores prevalências nos elementos Crenças, cultura e valores do paciente, Crenças e valores pessoais e, Intuição e Subjetividade. Conclusão: os resultados apontaram um equilíbrio entre critérios subjetivos da experiência profissional e objetivos da deontologia para a deliberação moral.Objetivo: identificar la asociación entre el distrés moral y los elementos de apoyo de la deliberación moral en los enfermeros brasileñas. Método: estudio transversal realizado con enfermeros brasileños que trabajan en servicios de salud de diferentes niveles de complejidad. El protocolo de investigación consistió en la Escala Brasileña de Distrés Moral en Enfermeros, un cuestionario sociodemográfico y laboral, y una lista de bases y elementos éticos utilizados para la deliberación moral. Para el análisis, se utilizó estadística descriptiva, prueba de chi-cuadrado y regresión de Poisson. Resultados: 1.226 enfermeros participaron en el estudio. Los 12 elementos asociados con el proceso de deliberación moral se clasificaron como importantes para el desempeño de los enfermeros, destacando la experiencia profesional adquirida, el Código de Ética/Derecho de Práctica Profesional y los principios éticos y bioéticos. La relación de distrés moral mostró una mayor prevalencia en los elementos Creencias, cultura y valores del paciente, Creencias y valores personales y, Intuición y Subjetividad. Conclusión: los resultados mostraron un equilibrio entre los criterios subjetivos de la experiencia profesional y los objetivos de ética para la deliberación moral.Objective: to identify the association between moral distress and the supporting elements of moral deliberation in Brazilian nurses. Method: a cross-sectional study conducted with Brazilian nurses working in health services at different complexity levels. The research protocol consisted of the Brazilian Scale of Moral Distress in Nurses, a sociodemographic and labor questionnaire, and a list of bases and ethical elements used for moral deliberation. For analysis, descriptive statistics, chi-square test, and Poisson regression were used. Results: 1,226 nurses took part in the study. The 12 elements associated with the moral deliberation process were classified as important for nurses’ actions, especially the professional experience acquired, code of ethics/law of professional practice, and ethical and bioethical principles. The relationship of moral distress showed higher prevalence in the Beliefs, culture and values of the patient, Beliefs and personal values, and Intuition and Subjectivity elements. Conclusion: the results showed a balance between the subjective criteria of professional experience and the objective ones of deontology for moral deliberation

Growth of Fungal Cells and the Production of Mycotoxins

Some filamentous fungi are able to grow in food and produce toxic metabolites. It occurs mainly in grains, cereals, oilseeds and some by-products. The growth of fungi in a particular food is governed largely by a series of physical and chemical parameters. The production of toxic metabolites is not confined to a single group of molds irrespective of whether they are grouped according to structure, ecology, or phylogenetic relationships. Mycotoxins can be carcinogenic and cause several harmful effects to both human and animal organisms, in addition to generating large economic losses. The major mycotoxins found in food are the aflatoxins, fumonisins, ochratoxins, patulin, zearalenone, and trichothecenes, generally stable at high temperatures and long storage periods. Considering the difficult prevention and control, international organizations for food safety establish safe levels of these toxins in food destined for both human and animal consumption. Good agricultural practices and control of temperature and moisture during storage are factors which contribute significantly to inhibit the production of mycotoxins. The use of some fungistatic products, such as essential oils and antioxidants, as well as physical, mechanical, chemical, or thermal processing, represents important methods to have the concentration of mycotoxins reduced in food

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Climate seasonality limits leaf carbon assimilation and wood productivity in tropical forests

The seasonal climate drivers of the carbon cycle in tropical forests remain poorly known, although these forests account for more carbon assimilation and storage than any other terrestrial ecosystem. Based on a unique combination of seasonal pan-tropical data sets from 89 experimental sites (68 include aboveground wood productivity measurements and 35 litter productivity measurements), their associated canopy photosynthetic capacity (enhanced vegetation index, EVI) and climate, we ask how carbon assimilation and aboveground allocation are related to climate seasonality in tropical forests and how they interact in the seasonal carbon cycle. We found that canopy photosynthetic capacity seasonality responds positively to precipitation when rainfall is  < 2000 mm yr⁻¹ (water-limited forests) and to radiation otherwise (light-limited forests). On the other hand, independent of climate limitations, wood productivity and litterfall are driven by seasonal variation in precipitation and evapotranspiration, respectively. Consequently, light-limited forests present an asynchronism between canopy photosynthetic capacity and wood productivity. First-order control by precipitation likely indicates a decrease in tropical forest productivity in a drier climate in water-limited forest, and in current light-limited forest with future rainfall  < 2000 mm yr⁻¹

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure &lt;= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Ontogeny of CX3CR1-EGFP expressing cells unveil microglia as an integral component of the postnatal subventricular zone

The full spectrum of cellular interactions within CNS neurogenic niches is still poorly understood. Only recently has the monocyte counterpart of the nervous system, the microglial cells, been described as an important cellular component in neurogenic niches. The present study sought to characterize the microglial population in the early postnatal subventricular zone (SVZ), the major site of postnatal neurogenesis, and in its anterior extension, the rostral migratory stream (RMS), a pathway for neuroblasts during their transit toward the olfactory bulb (OB) layers. Analysis of the transgenic mice strain that has one of the locus of the constitutively expressed fractalkine CX3CR1 receptor replaced by the gene encoding the green fluorescent protein (EGFP) circumvented the antigenic plasticity of the microglial cells. Here we show that common phenotypic markers of microglia do not reveal the full complement of these cells within the SVZ/RMS pathway. Remarkably, our analysis show that within the early SVZ/RMS pathway microglia are not proliferative and display a protracted development, retaining a more immature morphology than their counterparts outside germinal layers. Furthermore, during the first postnatal days microglia contact and phagocyte radial glia cells (RGs). Our results unveil microglial cells as a prominent component along the entire SVZ niche, together with neuroblasts and astroglial progenitors