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

Dipeptidyl peptidase IV inhibition attenuates blood pressure rising in young spontaneously hypertensive rats

Objectives The present study aimed to assess the effect of the specific dipeptidyl peptidase IV (DPPIV) inhibitor sitagliptin on blood pressure and renal function in young prehypertensive (5-week-old) and adult spontaneously hypertensive rats (SHRs; 14-week-old). Methods Sitagliptin (40 mg/kg twice daily) was given by oral gavage to young (Y-SHR + IDPPIV) and adult (A-SHR R IDPPIV) SHRs for 8 days. Kidney function was assessed daily and compared with age-matched vehicle-treated SHR (Y-SHR and A-SHR) and with normotensive Wistar-Kyoto rats (Y-WKY and A-WKY). Arterial blood pressure was measured in these animals at the end of the experimental protocol. Additionally, Na(+)/H(+) exchanger isoform 3 (NHE3) function and expression in microvilli membrane vesicles were assessed in young animals. Results Mean arterial blood pressure of Y-SHR + IDPPIV was significantly lower than that of Y-SHR (104 +/- 3 vs. 123 +/- 5 mmHg, P < 0.01) and was similar to Y-WKY (94 +/- 4 mmHg, P > 0.05). Compared to Y-SHR, Y-SHR + IDPPIV exhibited enhanced cumulative urinary flow and sodium excretion and decreased NHE3 activity and expression in proximal tubule microvilli. In the A-SHR, sitagliptin treatment had no significant effect on either renal function or arterial blood pressure. Conclusion Our data suggest that DPPIV inhibition attenuates blood pressure rising in young prehypertensive SHRs, partially by inhibiting NHE3 activity in renal proximal tubule. J Hypertens 29:520-528 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Mechanical Behavior of Inconel 625 at Elevated Temperatures

Inconel 625 is a nickel-based alloy that is mainly used in high-temperature applications. Inconel 625 exhibits an unstable plastic flow at elevated temperatures characterized by serrated yielding, well-known as the Portevin-Le Chatelier effect. The evaluation of the mechanical properties of Inconel 625 at high temperatures is the aim of this work. The tensile tests were executed in temperatures ranging from room temperature to 1000 &deg;C with strain rates of 2 &times; 10&minus;4 to 2 &times; 10&minus;3 s&minus;1. The creep tests were executed in the temperature range of 600&ndash;700 &deg;C and in the stress range of 500&ndash;600 MPa in a constant load mode. The optical and scanning electron microscopes were used for surface fracture observation. In the curves obtained at 200&ndash;700 &deg;C the serrated stress-strain behavior was observed, which was related to the dynamic strain aging effect. The yield strength and the elongation values show anomalous behavior as a function of the test temperature. An intergranular cracking was observed for a specimen tensile tested at 500 &deg;C that can be attributed to the decohesion of the carbides along the grain boundaries. The fracture surface of the specimen tensile tested at 700 &deg;C showed the predominance of transgranular cracking with tear dimples with a parabolic shape

Effect of Plasma Nitriding on the Creep and Tensile Properties of the Ti-6Al-4V Alloy

This work aimed to enhance the creep resistance of Ti-6Al-4V alloy treated by plasma nitriding. The nitriding was performed on specimens with a Widmanst&auml;tten microstructure for four hours at 690 &deg;C under a gas atmosphere containing Ar:N2:H2 (0.455:0.455:0.090). X-ray diffraction analysis showed that the &epsilon;-Ti2N and &delta;-TiN formed on the nitrided sample, in addition to the &alpha;-Ti and &beta;-Ti matrix phases. The layer thickness of this sample was about 1 &micro;m. Hot tensile tests were performed in the temperature range of 500 to 700 &deg;C on nitrided and non-nitrided samples, which indicated an increased strength of the nitrided samples. The same temperature range was used for the creep tests in a stress range of 125 to 319 MPa. The plasma-nitrided samples exhibited better creep resistance when compared to the untreated samples. This result was demonstrated by the decreased secondary creep rate and the increased final creep time. This improvement in the creep resistance appeared to be associated with the formation of the nitrided layer, which worked as a barrier to oxygen diffusion into the material and due to the formation of a surface residual compressive stress

Concentration—response curve to acetylcholine (A) and sodium nitroprusside (B) in aortic rings from SHAM, SHAM-TRA, OVX and OVX-TRA.

<p>The numbers shown in the legend represent the number of animals analyzed in each group. Results are expressed as means±SEM. Two-way ANOVA: *p<0.01 in comparison to SHAM, # p<0.01 in comparison to OVX.</p

Effect of L-NAME (100 μM) on the concentration—response curve of ACh in aortic rings from SHAM, SHAM-TRA, OVX and OVX-TRA: area under the curve (dAUC %).

<p>* p<0.05 OVX and OVX-TRA vs. SHAM and SHAM-TRA;</p><p>^# p<0.05 OVX-TRA vs. OVX. dAUC are expressed as a percentage of the corresponding AUC for L-NAME aortic rings.</p><p>Effect of L-NAME (100 μM) on the concentration—response curve of ACh in aortic rings from SHAM, SHAM-TRA, OVX and OVX-TRA: area under the curve (dAUC %).</p

Representative images of aortic slices from SHAM, SHAM-TRA, OVX and OVX-TRA rats, in the absence (upper panel) and presence (lower panel) of the superoxide dismutase mimetic, MnTMPyP (A). Quantification of fluorescence intensity emitted by DHE oxidation in aortic slices in the absence and presence of the MnTMPyP as an indicative of reactive oxygen species in SHAM, SHAM-TRA, OVX and OVX-TRA rats (B).

<p>The numbers shown in bars represent the number of animals analyzed in each group. Results are expressed as means±SEM. Two-way ANOVA: *p<0.01 in comparison to SHAM, # p<0.01 in comparison to OVX.</p