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 <= 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

Development of hepatorenal syndrome in bile duct ligated rats

AIM: To evaluate in bile duct ligated rats whether there were progressive alterations of renal function without changes in histopathology

Efeito prolongado de sistemas de preparo do solo com e sem cultivo de soqueira de cana crua em algumas propriedades físicas do solo Long-term effect of soil tillage systems with and without tillage of green-cane stump in soil physical properties

Este trabalho foi conduzido em Latossolo Vermelho distrófico típico, sob cultivo de cana crua, com o objetivo de avaliar o efeito prolongado de sistemas de preparo do solo, com e sem cultivo da soqueira, e épocas de amostragem sobre algumas propriedades físicas do solo. O delineamento experimental foi o de blocos ao acaso, em esquema de parcelas subsubdivididas, sendo os tratamentos principais quatro sistemas de preparo do solo: (i) controle da soqueira com duas gradagens, subsolagem e mais uma gradagem de nivelamento; (ii) controle da soqueira com herbicida e uma subsolagem; (iii) controle da soqueira com herbicida; (iv) controle da soqueira com herbicida, aração com arado de aivecas e uma gradagem de nivelamento. Os tratamentos secundários foram: com cultivo e sem cultivo da soqueira. Os tratamentos ternários foram as épocas de avaliação: dois dias antes e após a quarta colheita da cultura. A porosidade total, macroporosidade, microporosidade e densidade do solo foram avaliadas, além do perfilhamento e da produtividade da cultura. Após quatro sucessivas colheitas de cana crua, houve redução da macroporosidade com aumento da microporosidade nas camadas abaixo de 10 cm e aumento da densidade do solo entre 20 e 50 cm. A densidade do solo não foi alterada de modo consistente em função de todos os tratamentos testados. O cultivo da soqueira favoreceu o aumento da macroporosidade com decréscimo na microporosidade, e o efeito inverso foi observado após a colheita. Os sistemas de preparo do solo e de cultivo da soqueira não afetaram o perfilhamento e a produtividade da cultura.<br>This work was carried out at the field conditions in a Typic Haplustox soil with green-cane crop with the objective to evaluate long-term effect of soil tillage systems with and without tillage of stump in soil physical properties. A complete randomized blocks in split-split-plots arrangement of treatments were used. The principal treatments were four soil tillage systems: (i) control of stumps with two harrowing, subsoiling plus a levelling harrowing; (ii) control of stumps with herbicide and a subsoiling; (iii) control of stumps with herbicide; (iv) control of stumps with herbicide, subsoiling plus a levelling harrowing. Secondary treatments were stump tillage systems: with and without stump tillage. The split-split-plot treatments were the evaluation time: before and after the 4th cane harvest. Total porosity, macroporosity, microporosity and bulk density were evaluated, besides the tillering and yield of the crop. After four harvests of green-cane there were reduction of the macroporosity with increase of the microporosity in the soil layers below 10 cm, and an increase of soil bulk density in the layer between 20 and 50 cm. Soil bulk density wasn't altered in a consistent way as affected by all treatments. Stump tillage promoted an increased in the macroporosity with decrease of the microporosity, and the inverse effect was observed after the harvest. Soil tillage system and stump tillage didn't affect both tillering and yield of green-cane

The Brazilian Zika virus strain causes birth defects in experimental models.

Zika virus (ZIKV) is an arbovirus belonging to the genus Flavivirus (family Flaviviridae) and was first described in 1947 in Uganda following blood analyses of sentinel Rhesus monkeys. Until the twentieth century, the African and Asian lineages of the virus did not cause meaningful infections in humans. However, in 2007, vectored by Aedes aegypti mosquitoes, ZIKV caused the first noteworthy epidemic on the Yap Island in Micronesia. Patients experienced fever, skin rash, arthralgia and conjunctivitis. From 2013 to 2015, the Asian lineage of the virus caused further massive outbreaks in New Caledonia and French Polynesia. In 2013, ZIKV reached Brazil, later spreading to other countries in South and Central America. In Brazil, the virus has been linked to congenital malformations, including microcephaly and other severe neurological diseases, such as Guillain-Barré syndrome. Despite clinical evidence, direct experimental proof showing that the Brazilian ZIKV (ZIKV(BR)) strain causes birth defects remains absent. Here we demonstrate that ZIKV(BR) infects fetuses, causing intrauterine growth restriction, including signs of microcephaly, in mice. Moreover, the virus infects human cortical progenitor cells, leading to an increase in cell death. We also report that the infection of human brain organoids results in a reduction of proliferative zones and disrupted cortical layers. These results indicate that ZIKV(BR) crosses the placenta and causes microcephaly by targeting cortical progenitor cells, inducing cell death by apoptosis and autophagy, and impairing neurodevelopment. Our data reinforce the growing body of evidence linking the ZIKV(BR) outbreak to the alarming number of cases of congenital brain malformations. Our model can be used to determine the efficiency of therapeutic approaches to counteracting the harmful impact of ZIKV(BR) in human neurodevelopment

The Brazilian Zika virus strain causes birth defects in experimental models

Zika virus (ZIKV) is an arbovirus belonging to the genus Flavivirus (Family Flaviviridae) and was first described in 1947 in Uganda following blood analyses of sentinel Rhesus monkeys(1). Until the 20(th) century, the African and Asian lineages of the virus did not cause meaningful infections in humans. However, in 2007, vectored by Aedes aegypti mosquitoes, ZIKV caused the first noteworthy epidemic on the island of Yap in Micronesia(2). Patients experienced fever, skin rash, arthralgia and conjunctivitis(2). From 2013 to 2015, the Asian lineage of the virus caused further massive outbreaks in New Caledonia and French Polynesia. In 2013, ZIKV reached Brazil, later spreading to other countries in South and Central America(3). In Brazil, the virus has been linked to congenital malformations, including microcephaly and other severe neurological diseases, such as Guillain-Barré syndrome(4,5). Despite clinical evidence, direct experimental proof showing that the Brazilian ZIKV (ZIKV(BR)) strain causes birth defects remains missing(6). Here we demonstrate that the ZIKV(BR) infects fetuses, causing intra-uterine growth restriction (IUGR), including signs of microcephaly in mice. Moreover, the virus infects human cortical progenitor cells, leading to an increase in cell death. Finally, we observed that the infection of human brain organoids resulted in a reduction of proliferative zones and disrupted cortical layers. These results indicate that ZIKV(BR) crosses the placenta and causes microcephaly by targeting cortical progenitor cells, inducing cell death by apoptosis and autophagy, impairing neurodevelopment. Our data reinforce the growing body of evidence linking the ZIKV(BR) outbreak to the alarming number of cases of congenital brain malformations. Our model can be used to determine the efficiency of therapeutic approaches to counteracting the harmful impact of ZIKV(BR) in human neurodevelopment

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 <= 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.13Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt