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

Screening of yeast co‐culture using crude hydrolysate for co‐fermentation of pentose and hexose

The use of all sugars from biomass fractionation, i.e., hexoses and pentoses, is essential to develop feasible processes in a biorefinery context. Hexoses are converted into different products by most microorganisms, the main issue being the conversion of pentoses, especially when mixed with hexoses. Improving sugar conversion in co-fermentation is a major challenge that was explored in this work. Co-culture using S. cerevisiae and evolved K. marxianus strains was evaluated by a screening using 24 deep-well plates. Glucose depletion and 83% of xylose conversion were achieved from supplemented hemicellulosic hydrolysate, using 2/5 of deep-well volume filled with medium (at 150 rpm) and initial cell concentrations of 2.5 g/L for each yeast. The screening strategy provided reliable data that confirmed the co-culture as a promising approach for the co-assimilation of biomass-derived sugars. The importance of aeration control for effective xylose assimilation was also pointed out

Intensification of corn fiber saccharification using a tailor made enzymatic cocktail

The transition from an economic model based on resource extraction to a more sustainable and circular economy requires the development of innovative methods to unlock the potential of raw materials such as lignocellulosic biomasses. Corn fiber differs from more traditional lignocellulosic biomasses due to its high starch content, which provides additional carbohydrates for fermentation-based biomanufacturing processes. Due to its unique chemical composition, this study focused on the development of a tailor made enzymatic cocktail for corn fiber saccharification into monosaccharides. Three commercially available hydrolytic enzymes (Cellic® CTec2, Pentopan® Mono BG, and Termamyl® 300 L) were combined to hydrolyze the polysaccharide structure of the three main carbohydrate fractions of corn fiber (cellulose, hemicellulose and starch, respectively). Prior to saccharification, corn fiber was submitted to a mild hydrothermal pretreatment (30 min at 100 oC). Then, two experimental designs were used to render an enzymatic cocktail capable of providing efficient release of monosaccharides. Using 60 FPU/g DM of Cellic® CTec2 and 4.62 U/g DM of Termamyl® 300 L, without addition of Pentopan® Mono BG, resulted in the highest efficiencies for glucose and xylose release (66% and 30%, respectively). While higher enzyme dosages could enhance the saccharification efficiency, adding more enzymes would have a more pronounced effect on the overall process costs rather than in increasing the efficiency for monosaccharides release. The results revealed that the recalcitrance of corn fiber poses a problem for its full enzymatic degradation. This fact combined with the unique chemical composition of this material, justify the need for developing a tailor made enzymatic cocktail for its degradation. However, attention should also be given to the pretreatment step to reduce even more the recalcitrance of corn fiber and improve the performance of the tailored cocktail, as a consequence

Evaluation of Consolidated Bioprocessing of Sugarcane Biomass by a Multiple Hydrolytic Enzyme Producer <i>Saccharomyces</i> Yeast

Overcoming key bottlenecks for 2G ethanol production, such as the most suitable biomass pretreatment, process layout, and appropriate microorganism, is crucial to achieve a technically and economically feasible technology. The consolidated bioprocessing (CBP) is an approach that embodies one single step of enzyme production, biomass hydrolysis, and sugars fermentation. In this work, the CBP using S. cerevisiae AC14, a recombinant strain capable of secreting 7 different lignocellulosic enzymes and ferment xylose and glucose, was investigated in synthetic medium (cellobiose, corncob xylan, glucose, and xylose) and in industrial medium consisting of the solid fraction of hydrothermally pretreated sugarcane bagasse and its liquor. Results obtained were promising, with ethanol productivity of 4.46 g/L/h and complete hydrolysis of cellobiose and corncob xylan. In real industrial medium, 1.86 g/L/h of ethanol was reached, with partial conversion of both solid and liquid fractions. Further strategies to enhance enzymes access to complex substrates can improve process feasibility. Graphical Abstract: [Figure not available: see fulltext.

Repeated batches as a strategy for high 2G ethanol production from undetoxified hemicellulose hydrolysate using immobilized cells of recombinant Saccharomyces cerevisiae in a fixed-bed reactor

Background: The search for sustainable energy sources has become a worldwide issue, making the development of efficient biofuel production processes a priority. Immobilization of second-generation (2G) xylose-fermenting Saccharomyces cerevisiae strains is a promising approach to achieve economic viability of 2G bioethanol production from undetoxified hydrolysates through operation at high cell load and mitigation of inhibitor toxicity. In addition, the use of a fixed-bed reactor can contribute to establish an efficient process because of its distinct advantages, such as high conversion rate per weight of biocatalyst and reuse of biocatalyst. Results: This work assessed the influence of alginate entrapment on the tolerance of recombinant S. cerevisiae to acetic acid. Encapsulated GSE16-T18SI.1 (T18) yeast showed an outstanding performance in repeated batch fermentations with cell recycling in YPX medium supplemented with 8 g/L acetic acid (pH 5.2), achieving 10 cycles without significant loss of productivity. In the fixed-bed bioreactor, a high xylose fermentation rate with ethanol yield and productivity values of 0.38 gethanol/gsugars and 5.7 g/L/h, respectively were achieved in fermentations using undetoxified sugarcane bagasse hemicellulose hydrolysate, with and without medium recirculation. Conclusions: The performance of recombinant strains developed for 2G ethanol production can be boosted strongly by cell immobilization in alginate gels. Yeast encapsulation allows conducting fermentations in repeated batch mode in fixed-bed bioreactors with high xylose assimilation rate and high ethanol productivity using undetoxified hemicellulose hydrolysate.status: publishe

Importância do raio X e exame físico no diagnóstico da artrite psoriática e sua prevalência no Hospital Universitário Evangélico de Curitiba (HUEC) The importance of radiologic evaluation and physical examination in diagnosis of psoriatic arthritis and its prevalance in the Hospital Universitário Evangélico de Curitiba

FUNDAMENTOS: A artrite psoriática (AP) é doença inflamatória associada com a psoríase da pele ou das unhas, com fator reumatóide (FR) negativo e ausência de nódulos reumatóides. Pode ser extremamente agressiva, deixando o paciente incapacitado para realizar funções do dia-a-dia. A prevalência populacional é muito variável; historicamente oscila entre 2,6% e 7%, mas estudos recentes demonstram porcentagem variável de 23 a 69% na população com psoríase. O diagnóstico é de exclusão e, se realizado na fase inicial, oferece possibilidade de tratamento mais adequado, evitando complicações. O que define a presença da artrite é o exame físico adequado das articulações, já que o raio X pode estar normal. OBJETIVO: Este estudo tem a finalidade de avaliar a importância do raio X e do exame físico no diagnóstico da AP e sua prevalência nos pacientes com psoríase cutânea e ungueal do Hospital Universitário Evangélico de Curitiba. MATERIAL E MÉTODOS: Trinta pacientes com psoríase em acompanhamento nesse serviço foram submetidos a anamnese e exame físico minuciosos. Eles foram questionados quanto a alterações articulares, tempo e severidade de doença e comprometimento ungueal. Os que apresentavam queixas articulares foram encaminhados para investigação por exames complementares: hemograma, FR, VHS, e raio X da articulação comprometida. RESULTADOS: A maioria dos pacientes (56,5%) referiu atralgia; contudo apenas três apresentavam artrite. Dos indivíduos com AP, um mostrou raio X normal, mas o exame físico estava alterado. CONCLUSÃO: O exame físico é fundamental para diagnóstico da AP; o raio X não. A prevalência de AP foi de 10%.<br>BACKGROUND: Psoriatic arthritis (PA) is an inflammatory disorder associated with skin and nail disease, negative rheumatoid factor (RF) and absence of rheumatoid nodules. It can be a devastating and incapacitating condition. Its prevalence is highly variable, ranging from 2,6 to 7%; however, recent data shows prevalence as high as 23 to 69%. Its diagnosis is one of exclusion, and when detected early in the course of the disease gives chance to adequate treatment, thus avoiding its sequelae. The diagnosis is made by physical examination, laboratory and radiological evaluation. A normal radiological finding does not exclude the disease. OBJECTIVE: This study aims to evaluate the importance of a detailed physical examination associated with radiological findings in the diagnosis of PA and its prevalence in our institution. METHODS: Thirty patients with skin psoriasis were submitted to a thorough physical examination and radiological evaluation. All patients were inquired about articular complaints, time and severity of skin and nail disease. Those that presented any articular symptom were submitted to a laboratory evaluation with: Complete Blood Count (CBC), RF, Erythrocyte Sedimentation Rate (ESR) and radiography of the involved joint. RESULTS: The majority of patients (56,5%) presented arthralgia; however, only three patients had arthritis. Of those 3 that had PA, one presented a normal radiography but with an altered physical examination. CONCLUSION: The physical examination is an extremely important tool in the evaluation of patients with psoriasis. The radiological evaluation is not as important as the physical examination. The prevalence of PA was 10%

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