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Chagas disease (CD) continues to be a neglected infectious disease with one of the largest burdens globally. Despite the modest cure rates in adult chronic patients and its safety profile, benznidazole (BNZ) is still the drug of choice. Its current recommended dose is based on nonrandomized studies, and efficacy and safety of the optimal dose of BNZ have been scarcely analyzed in clinical trials. MULTIBENZ is a phase II, randomized, noninferiority, double-blind, multicenter international clinical trial. A total of 240 patients with Trypanosoma CD in the chronic phase will be recruited in four different countries (Argentina, Brazil, Colombia, and Spain). Patients will be randomized to receive BNZ 150 mg/day for 60 days, 400 mg/day for 15 days, or 300 mg/day for 60 days (comparator arm). The primary outcome is the efficacy of three different BNZ therapeutic schemes in terms of dose and duration. Efficacy will be assessed according to the proportion of patients with sustained parasitic load suppression in peripheral blood measured by polymerase chain reaction. The secondary outcomes are related to pharmacokinetics and drug tolerability. The follow-up will be 12 months from randomization to end of study participation. Recruitment was started in April 2018. This is a clinical trial conducted for the assessment of different dose schemes of BNZ compared with the standard treatment regimen for the treatment of CD in the chronic phase. MULTIBENZ may help to clarify which is the most adequate BNZ regimen in terms of efficacy and safety, predicated on sustained parasitic load suppression in peripheral blood. ClinicalTrials.gov, NCT03191162. Registered on 19 June 2017.

This work was funded by a grant from Cárnicas Joselito SA through research project FUO-222-16 to University of Oviedo and Universidad Complutense de Madrid, and by grant IDI/2018/000120 from Programa de Ayudas a Gru-pos de Investigación del Principado de Asturias.

The authors thank funding from Convocatoria 2017 de Ayudas Destinadas a Financiar la Realizacin de Proyectos de Investigacin Industrial y Desarrollo Experimental a las Empresas de la Comunidad Autnoma de Extremadura (FUO-181-18) and [FUO-181-18]; Ayudas para Grupos de Investigacin de Organismos del Principado de Asturias [AYUD/2021/51347, PAPI-20-PF-20, PAPI-21-PF-16]

A hardwood kraft lignin was oxidized in alkaline medium to obtain phenolic compounds (syringaldehyde, vanillin and its acids). To avoid lignin condensation, the lignin was precipitated from a black liquor with a calcium salt dissolved in a water soluble alcohol. Oxygen was the oxidant employed, and copper (II) and cobalt (II) salts were used as catalysts. Effect of temperature, reaction time, oxygen pressure, alkali concentration and catalyst on yield and product distribution were studied. In all the range of variables lignin conversion and aldehyde yield remains low and the more important effect on aldehyde yield was due to the alkali concentration, which must be fixed at about 2 N. The precipitation method did not significantly increase the aldehyde yield, in contrast with the results of nitrobenzene and CuO oxidations. In catalyzed oxidations, no increase in phenolic aldehydes was observed and, with some catalyst, the conversion into phenolic derivatives was reduced. Lignin conversion into low molecular weight products is responsible for the low phenolic product yield and the type of catalyst could lead the oxidation into phenolic products or into low molecular weight acids.

In this trial, administering aspirin before surgery and during the early postsurgical period did not affect the rate of death or nonfatal MI but increased the risk of major bleeding. This was true in patients who had not been taking aspirin and in those on a long-term aspirin regimen. Myocardial infarction is the most common major vascular complication that occurs after noncardiac surgery. 1 – 3 Noncardiac surgery is associated with platelet activation, 4 and coronary-artery thrombus may be a mechanism of perioperative myocardial infarction. 5 , 6 Aspirin inhibits platelet aggregation, 7 and the perioperative administration of aspirin may prevent major vascular complications by inhibiting thrombus formation. 8 In a meta-analysis of data from large, randomized trials involving more than 110,000 patients who were not undergoing surgery, the use of aspirin was shown to prevent myocardial infarction and major vascular events. 9 High-dose aspirin has not been shown to be superior to low-dose aspirin in preventing . . .

In this trial, clonidine, an α2-adrenergic agonist, did not reduce the rate of death or MI among patients undergoing noncardiac surgery. Clonidine did increase the risk of perioperative hypotension, bradycardia, and nonfatal cardiac arrest. Myocardial infarction is the most common major vascular complication of surgery and is associated with substantial mortality. 1 During and after noncardiac surgery, there is marked activation of the sympathetic nervous system, which can lead to a mismatch between the supply of and demand for myocardial oxygen and to subsequent myocardial infarction. 2 – 4 We previously reported that perioperative administration of a high-dose, long-acting beta-blocker (initiated 2 to 4 hours before surgery and continued after surgery) reduced the risk of myocardial infarction but increased the risk of death, stroke, and clinically important hypotension. 5 Clonidine, an α 2 -adrenergic agonist, blunts central sympathetic . . .

Background Chagas disease (CD) continues to be a neglected infectious disease with one of the largest burdens globally. Despite the modest cure rates in adult chronic patients and its safety profile, benznidazole (BNZ) is still the drug of choice. Its current recommended dose is based on nonrandomized studies, and efficacy and safety of the optimal dose of BNZ have been scarcely analyzed in clinical trials. Methods/design MULTIBENZ is a phase II, randomized, superiority, double-blind, multicenter international clinical trial. A total of 240 patients with Trypanosoma CD in the chronic phase will be recruited in four different countries (Argentina, Brazil, Colombia, and Spain). Patients will be randomized to receive BNZ 150 mg/day for 60 days, 400 mg/day for 15 days, or 300 mg/day for 60 days (comparator arm). The primary outcome is the efficacy of three different BNZ therapeutic schemes in terms of dose and duration. Efficacy will be assessed according to the proportion of patients with sustained parasitic load suppression in peripheral blood measured by polymerase chain reaction. The secondary outcomes are related to pharmacokinetics and drug tolerability. The follow-up will be 12 months from randomization to end of study participation. Recruitment was started in April 2018. Conclusion This is a clinical trial conducted for the assessment of different dose schemes of BNZ compared with the standard treatment regimen for the treatment of CD in the chronic phase. MULTIBENZ may help to clarify which is the most adequate BNZ regimen in terms of efficacy and safety, predicated on sustained parasitic load suppression in peripheral blood. Trial registration ClinicalTrials.gov, NCT03191162 . Registered on 19 June 2017.

Kenaf (Hibiscus cannabinus L.) is an annual plant which produces a very high fiber yield per hectare and has demonstrated to be a suitable material for pulping. The crop conditions influence fiber production, but there is no information about their effect on pulp quality. The aim of this work was to study the effect of kenaf varieties and crop conditions (watering dose and harvesting time) on sulfate pulp quality. The study has been made on bast fiber sulfate pulps due to their high added value. The quality criteria were fiber dimensions, chemical composition and pulp quality. Kenaf variety or crop conditions have significant effect on fiber dimensions, holocellulose content, kappa number and breaking strength. To obtain high fiber yield and good delignified pulps it is recommended to grow the Salvador variety and to employ advance harvesting.

Cardiopulmonary bypass initiates a systemic inflammatory response syndrome that is associated with postoperative morbidity and mortality. Steroids suppress inflammatory responses and might improve outcomes in patients at high risk of morbidity and mortality undergoing cardiopulmonary bypass. We aimed to assess the effects of steroids in patients at high risk of morbidity and mortality undergoing cardiopulmonary bypass. The Steroids In caRdiac Surgery (SIRS) study is a double-blind, randomised, controlled trial. We used a central computerised phone or interactive web system to randomly assign (1:1) patients at high risk of morbidity and mortality from 80 hospital or cardiac surgery centres in 18 countries undergoing cardiac surgery with the use of cardiopulmonary bypass to receive either methylprednisolone (250 mg at anaesthetic induction and 250 mg at initiation of cardiopulmonary bypass) or placebo. Patients were assigned with block randomisation with random block sizes of 2, 4, or 6 and stratified by centre. Patients aged 18 years or older were eligible if they had a European System for Cardiac Operative Risk Evaluation of at least 6. Patients were excluded if they were taking or expected to receive systemic steroids in the immediate postoperative period or had a history of bacterial or fungal infection in the preceding 30 days. Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcomes were 30-day mortality and a composite of death and major morbidity (ie, myocardial injury, stroke, renal failure, or respiratory failure) within 30 days, both analysed by intention to treat. Safety outcomes were also analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00427388. Patients were recruited between June 21, 2007, and Dec 19, 2013. Complete 30-day data was available for all 7507 patients randomly assigned to methylprednisolone (n=3755) and to placebo (n=3752). Methylprednisolone, compared with placebo, did not reduce the risk of death at 30 days (154 [4%] vs 177 [5%] patients; relative risk [RR] 0·87, 95% CI 0·70–1·07, p=0·19) or the risk of death or major morbidity (909 [24%] vs 885 [24%]; RR 1·03, 95% CI 0·95–1·11, p=0·52). The most common safety outcomes in the methylprednisolone and placebo group were infection (465 [12%] vs 493 [13%]), surgical site infection (151 [4%] vs 151 [4%]), and delirium (295 [8%] vs 289 [8%]). Methylprednisolone did not have a significant effect on mortality or major morbidity after cardiac surgery with cardiopulmonary bypass. The SIRS trial does not support the routine use of methylprednisolone for patients undergoing cardiopulmonary bypass. Canadian Institutes of Health Research.