Clinical, laboratory and immunohistochemical characterization of in situ pulmonary arterial thrombosis in fatal COVID-19

Background: COVID-19 patients carry an increased rate of thrombosis. It is controversial to which extent thrombi in the pulmonary arterial tree really contribute to disease severity with hypoxemia secondary to microvascular/lung parenchymal damage with viral alveolitis considered to play the main role in critical disease. Objectives: The primary objective was to compare post-mortem lung disease from fatal COVID-19 pneumonia in patients with macroscopically evident pulmonary arterial tree thrombosis and patients without, by characterizing the immunohistochemical nature of thrombi, and by comparing clinical and laboratory features of these patients with other COVID-19 patients who died but without evidence of pulmonary arterial thrombosis (controls). Patients and methods: 13 COVID-19 pneumonia cases (mean age ± standard deviation: 74 ± 6.5 years) with macroscopically visible pulmonary arterial thrombosis were compared to 14 controls. Hematoxylin and Eosin stained slides were reviewed choosing those with visible pulmonary thrombi which were further characterized by immunohistochemistry, in particular for the inflammatory infiltrates. Ante mortem serum markers relevant to pulmonary embolism were evaluated in both groups. Results: Twenty arterial thrombi (5 cases with multiple thrombi) were selected for study and were composed by white blood cells (WBC) [median, IQR range: 10 % (5–12.25)], mainly neutrophils [58 % (35.2–64.5)]. Cases with thrombosis showed significantly higher levels of platelet count [median, IQR range: 195000/mmc (157750–274,500) vs 143,500 (113000–175,250), p = 0.011], LDH [854 U/L (731–1315) vs 539 (391.5–660), p = 0.003] at admission, and D-dimer at ICU transfer [25,072 FEU (6951–50,531) vs 1024 (620–5501), p = 0.003]. Conclusions: Immunothrombotically driven arterial thrombi in COVID-19 patients are associated with D-Dimer and LDH elevations, thus linking inflammation, coagulopathy and organ damage in fatal COVID-19

Exploring the boundaries in an interdisciplinary context through the Family Resemblance Approach: The Dialogue Between Physics and Mathematics

Among the relevant aspects of the family resemblance approach (FRA), our study focuses on the potential of the approach to elaborate on disciplinary identities in an interdisciplinary context, specifically regarding the interplay between physics and mathematics. We present and discuss how the FRA wheel can be used and intertwined with the framework of boundary objects and boundary crossing mechanisms (Akkerman & Bakker, Review of Educational Research, 81, 132–169, 2011), which is well-known in STEM education for dealing with interdisciplinarity. The role of the FRA discussed in the article is dual: both practical and theoretical. It is practical in that we show how its use, in combination with the Akkerman and Bakker framework, appears effective in fostering productive discussions among prospective teachers on disciplinary identities and interdisciplinarity in historical cases. It is theoretical in that the combination of the two frameworks provides the vocabulary to characterise the ‘ambiguous nature’ of interdisciplinarity: like boundaries, interdisciplinarity both separates disciplines, making their identities emerge, and connects them, fostering mechanisms of crossing and transgressing the boundaries. This empirical study reveals how the theoretical elaboration took advantage of the prospective teachers’ contributions. We initially presented the FRA to characterise disciplinary identities, but the prospective teachers highlighted its potential to characterise also the boundary zone and the dialogue between physics and mathematics. The data analysis showed that the combination of the two frameworks shaped a complex learning space where there was room for very different epistemic demands of the prospective teachers: from those who feel better within the identity cores of the disciplines, to those who like to inhabit the boundary zone and others who like to re-shape boundary spaces and move dynamically across them

Elastase-2 Knockout Mice Display Anxiogenic- and Antidepressant-Like Phenotype : Putative Role for BDNF Metabolism in Prefrontal Cortex

Several pieces of evidence indicate that elastase-2 (ELA2; chymotrypsin-like ELA2) is an alternative pathway to the generation of angiotensin II (ANGII). Elastase-2 knockout mice (ELA2KO) exhibit alterations in the arterial blood pressure and heart rate. However, there is no data on the behavioral consequences of ELA2 deletion. In this study, we addressed this question, submitting ELA2KO and wild-type (WT) mice to several models sensitive to anxiety- and depression-like, memory, and repetitive behaviors. Our data indicates a higher incidence of barbering behavior in ELA2KO compared to WT, as well as an anxiogenic phenotype, evaluated in the elevated plus maze (EPM). While a decrease in locomotor activity was observed in ELA2KO in EPM, this feature was not the main source of variation in the other parameters analyzed. The marble-burying test (MBT) indicated increase in repetitive behavior, observed by a higher number of buried marbles. The actimeter test indicated a decrease in total activity and confirmed the increase in repetitive behavior. The spatial memory was tested by repeated exposure to the actimeter in a 24-h interval. Both ELA2KO and WT exhibited decreased activity compared to the first exposure, without any distinction between the genotypes. However, when submitted to the cued fear conditioning, ELA2KO displayed lower levels of freezing behavior in the extinction session when compared to WT, but no difference was observed during the conditioning phase. Increased levels of BDNF were found in the prefrontal cortex but not in the hippocampus of ELA2KO mice compared to WT. Finally, in silico analysis indicates that ELA2 is putatively able to cleave BDNF, and incubation of the purified enzyme with BDNF led to the degradation of the latter. Our data suggested an anxiogenic- and antidepressant-like phenotype of ELA2KO, possibly associated with increased levels of BDNF in the prefrontal cortex.Peer reviewe

A cadeia produtiva da carne bovina brasileira e a segurança alimentar: um olhar para os insumos produtivos.

The alignment of food production systems with the trends and demands of the world population plays an important global role. This study aims to discuss the convergence of trends related to the Brazilian beef cattle supply chain from a food security perspective. Therefore, it includes important reports on the future of this supply chain and its input production, taking on a qualitative approach to consider trends in animal health, genetics, nutrition, forage, and farm machinery in terms of the development of Brazilian agriculture and the future of food and agribusiness. From a managerial point of view, it was possible to provide information capable of leading to a sustainable understanding. Thus, a content analysis of the documents was carried out, coding them through the Sustainable Development Goals and categorizing them by taking into account the 2030 Agenda?s five Ps (people, planet, prosperity, peace, and partnerships). Along this line, the discussion highlights the themes of poverty and climate change, emphasizing them with regard to the categorization social aspects ? the P of people). Future trends will require a workforce prepared to deal with the additional limitations that can arise with the use of new technologies as productivity increases

Effect of hyperbaric oxygenation and gemcitabine on apoptosis of pancreatic ductal tumor cells in vitro.

Gemcitabine is first-line therapy for advanced pancreatic ductal adenocarcinoma (PDAC) with a poor survival and response rate. Hyperbaric oxygenation (HBO) enhances delivery of oxygen to hypoxic tumor cells and increases their susceptibility to cytotoxic effects of chemotherapy. We hypothesized that the anticancer activity of gemcitabine (GEM) may be enhanced if tumor cells are placed in an oxygen-rich environment. The present study evaluated the effects of gemcitabine, HBO and their combination on apoptosis of tumor cells. Materials and Methods: PANC-1 and AsPc-1 PDAC tumor cell lines wereused. Cultured tumor cells were treated with GEM at its growth-inhibitory concentration (IC50) and HBO at 2.5 ATA for 90 min or a combination of both (HBO then GEM and GEM then HBO). Twenty-four hours later, apoptotic cells ineach group were analyzed and the apoptotic index (AI) wascalculated. Results: PANC-1 cell line: HBO alone had noeffect on AI: 6.5\ub10.1 vs. 5.9\ub10.1. HBO before and aftergemcitabine did not further increase AI: 8.2\ub10.1 (HBOGEM),8.5\ub10.1 (GEM-HBO) vs. 8.1\ub10.1 (GEM). The combination of HBO and gemcitabine significantly increased AI: 10.7\ub10.02 (p<0.001 vs. all groups). AsPc-1 cell line: HBO-alone had no effect on AI: 5.9\ub10.1 vs. 5.9\ub10.1. HBO before and after gemcitabine did not further increase AI:8.2\ub10.1 (HBO-GEM), 8.4\ub10.1 (GEM-HBO) vs. 8.0\ub10.1 (GEM). The combination of HBO and gemcitabine significantly increased AI: 9.7\ub10.1 (p<0.001 vs. all groups). Conclusion: HBO-alone, whether administered before and after gemcitabine has no effect on apoptosis of PDAC cellsin vitro. HBO significantly enhanced gemcitabine-induced apoptosis when administered during gemcitabine. Our findings suggest that the time window would be critical for using HBO as adjuvant to chemotherapy

Eficácia de herbicidas pré-emergentes no controle de caruru resistente ao glifosato e efeito carryover sobre azevém em sucessão.

O objetivo do trabalho foi investigar o efeito residual de herbicidas pré-emergentes no controle de caruru e o efeito carryover sobre azevém em sucessão ao cultivo de soja

Global structural integrity and effective connectivity in patients with disorders of consciousness

Background: Previous studies have separately reported impaired functional, structural, and effective connectivity in patients with disorders of consciousness (DOC). The perturbational complexity index (PCI) is a transcranial magnetic stimulation (TMS) derived marker of effective connectivity. The global fractional anisotropy (FA) is a marker of structural integrity. Little is known about how these parameters are related to each other. Objective: We aimed at testing the relationship between structural integrity and effective connectivity. Methods: We assessed 23 patients with severe brain injury more than 4 weeks post-onset, leading to DOC or locked-in syndrome, and 14 healthy subjects. We calculated PCI using repeated single pulse TMS coupled with high-density electroencephalography, and used it as a surrogate of effective connectivity. Structural integrity was measured using the global FA, derived from diffusion weighted imaging. We used linear regression modelling to test our hypothesis, and computed the correlation between PCI and FA in different groups. Results: Global FA could predict 74% of PCI variance in the whole sample and 56% in the patients' group. No other predictors (age, gender, time since onset, behavioural score) improved the models. FA and PCI were correlated in the whole population (r = 0.86, p < 0.0001), the patients, and the healthy subjects subgroups. Conclusion: We here demonstrated that effective connectivity correlates with structural integrity in brain-injured patients. Increased structural damage level decreases effective connectivity, which could prevent the emergence of consciousness