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Graphical abstract Highlights • A simple phenomenological kinetic model for corn stover saccharification is proposed. • Cellulase depolymerisation and glucose production from cellobiose are considered. • Cellulase and β-glucosidase deactivation explains fast reduction of reaction rates. • Overcrowding effects in cellulases are reflected in the model. Abstract A physico-chemical kinetic model for the hydrolysis of pre-treated corn stover is proposed. This model takes into account two reactions in series, the hydrolysis of cellulose to cellobiose and the production of glucose from cellobiose. Experiments have been carried out with an industrial enzymatic cocktail from Trichoderma reesei containing endo and exoglucanases and a very low activity of β-glucosidase. Kinetic parameters were calculated by fitting the proposed model to experimental data of cellulose and glucose concentrations with time. The kinetic parameters fulfilled all relevant statistical and physical criteria. The kinetic model has been validated with published saccharification data regarding differently pre-treated corn stover and enzymatic cocktail, in this case with a very high β-glucosidase activity (as it is common in modern industrial cellulase cocktails). In both cases, the kinetic model proposed could be fitted very appropriately to cellulose hydrolysis data. [ABSTRACT FROM AUTHOR]

The inhibition of the enzymatic saccharification of acid pretreated corn stover (PCS) biomass due to several compounds either present in PCS or produced during saccharification has been studied. The prospective inhibitors tested were glucose (≤110 g L −1 ), celobiose (≤24 g L −1 ), xylose (≤50 g L −1 ), arabinose (≤1.5 g L −1 ), furfural (≤2 g L −1 ), hydroxymethylfurfural (≤1 g L −1 ), acetic acid (≤4 g L −1 ), and lignin (≤50 g L −1 ). Each of these compounds was added at three different concentrations, being the concentration intervals different according to standard maximum concentrations of such compounds in the reaction medium, previously measured and described in literature. In addition, these experiments were employed to evaluate the standard error present during the evaluation of the results obtained in the inhibition reactions. Those results show that significant inhibition was only detected for lignin (more than 25 g L −1 ) and it was also appreciable for glucose at high concentrations (above 75 g L −1 ), although it was not remarkable at medium concentrations (40 g L −1 ). On the other hand, neither of the remaining compounds tested presented any significant inhibitory effect at the usual process concentration range. [ABSTRACT FROM AUTHOR]

Background: Steroids may improve outcomes in high-risk patients undergoing cardiac surgery with the use of cardiopulmonary bypass (CBP). There is a need\ for a large randomized controlled trial to clarify the effect of steroids in such patients. Methods: We plan to randomize 7,500 patients with elevated European System for Cardiac Operative Risk Evaluation who are undergoing cardiac surgery with the use of CBP to methylprednisolone or placebo. The first coprimary outcome is 30-day all-cause mortality, and the most second coprimary outcome is a composite of death, MI, stroke, renal failure, or respiratory failure within 30 days. Other outcomes include a composite of MI or mortality at 30 days, new onset atrial fibrillation, bleeding and transfusion requirements, length of intensive care unit stay and hospital stay, infection, stroke, wound complications, gastrointestinal complications, delirium, postoperative insulin use and peak blood glucose, and all-cause mortality at 6 months. Results: As of October 22, 2013, 7,034 patients have been recruited into SIRS in 82 centers from 18 countries. Patient’s mean age is 67.3 years, and 60.4% are male. The average European System for Cardiac Operative Risk Evaluation is 7.0 with 22.1% having an isolated coronary artery bypass graft procedure, and 66.1% having a valve procedure. Conclusions: SIRS will lead to a better understanding of the safety and efficacy of prophylactic steroids for cardiac surgery requiring CBP. [Copyright &y& Elsevier]

Objective: To determine the impact of early mobilisation (EM) on total mortality and non-fatal re-infarction after acute myocardial infarction (AMI). Design: Systematic review and meta-analysis. Data sources: MEDLINE, CINAHL, HealthStar, EMBASE, the Cochrane Library Controlled Trials Registry and experts. Methods: Target studies included published and unpublished experimental, controlled studies in any language comparing AMI patients allocated to any in-hospital early mobilisation or a control/standard treatment. Two reviewers independently assessed study eligibility and quality and performed data extraction. We calculated relative risks (RRs) and 95% confidence intervals (CIs) using the random-effects model. Outcomes: All-cause mortality or re-infarction up to 1-year post-AMI. Results: Out of 385 potentially relevant studies, 14 met our eligibility criteria (13 published before 1983). There were 149 deaths (9.3% of 1607) and 82 non-fatal re-infarctions (5.2% of 1580) among post-AMI patients receiving EM, compared with 179 deaths (11.6% of 1541) and 80 non-fatal re-infarctions (5.3% of 1518) among AMI patients receiving control treatment (RR=0.85, 95% CI 0.68, 1.05 and RR=1.02, 95% CI 0.75, 1.39 respectively). Conclusion: Our meta-analysis demonstrated a trend towards decreased mortality with EM after AMI. However, there is uncertainty about early mobilisation and more research should be developed having into account all kind of differences among patients receiving treatment after AMI worldwide. [Copyright &y& Elsevier]

The Tec family non-receptor tyrosine kinase Itk is expressed in T cells, natural killer (NK) cells and mast cells. The role of this multidomain kinase in T cells has been linked to T-cell receptor–CD3 (TCR–CD3) signaling and Itk regulates and amplifies signals through the costimulatory receptors CD28 and CD2. Itk binds a specific subset of membrane inositol phospholipids through its pleckstrin homology (PH) domain; it forms functional molecular complexes with a variety of signaling proteins through its Tec homology (TH), Src homology 3 (SH3) and SH2 domains; and it phosphorylates several protein substrates on tyrosine residues in cells. Among >500 protein kinases expressed in the human proteome, we propose that Itk is a validated T-cell target suitable for pharmaceutical intervention. Targeted disruption of protein–protein interactions between Itk and some of its binding partners, and inhibition of the intrinsic kinase activity of Itk, could provide platforms through which to alter T-cell activation in immunological and inflammatory disorders. [Copyright &y& Elsevier]

Studies vasovagal susceptibility to nitrate or isoproterenol head-up tilt. Key issues of interest; Analysis of pertinent topics and relevant issues; Implications on cardiology.

Optimised use of kidney function information might improve cardiac risk prediction in noncardiac surgery. In 35,815 patients from the VISION cohort study and 9219 patients from the POISE-2 trial who were ≥45 yr old and underwent nonurgent inpatient noncardiac surgery, we examined (by age and sex) the association between continuous nonlinear preoperative estimated glomerular filtration rate (eGFR) and the composite of myocardial injury after noncardiac surgery, nonfatal cardiac arrest, or death owing to a cardiac cause within 30 days after surgery. We estimated contributions of predictive information, C-statistic, and net benefit from eGFR and other common patient and surgical characteristics to large multivariable models. The primary composite occurred in 4725 (13.2%) patients in VISION and 1903 (20.6%) in POISE-2; in both studies cardiac events had a strong, graded association with lower preoperative eGFR that was attenuated by older age (P interaction <0.001 for VISION; P interaction =0.008 for POISE-2). For eGFR of 30 compared with 90 ml min−1 1.73 m−2, relative risk was 1.49 (95% confidence interval 1.26–1.78) at age 80 yr but 4.50 (2.84–7.13) at age 50 yr in female patients in VISION. This differed modestly (but not meaningfully) in men in VISION (P interaction =0.02) but not in POISE-2 (P interaction =0.79). eGFR contributed the most predictive information and mean net benefit of all predictors in both studies, most C-statistic in VISION, and third most C-statistic in POISE-2. Continuous preoperative eGFR is among the best cardiac risk predictors in noncardiac surgery of the large set examined. Along with its interaction with age, preoperative eGFR would improve risk calculators. ClinicalTrials.gov NCT00512109 (VISION) and NCT01082874 (POISE-2). [ABSTRACT FROM AUTHOR]

Treatment with benznidazole for chronic Chagas disease is associated with low cure rates and substantial toxicity. We aimed to compare the parasitological efficacy and safety of 3 different benznidazole regimens in adult patients with chronic Chagas disease. The MULTIBENZ trial was an international, randomised, double-blind, phase 2b trial performed in Argentina, Brazil, Colombia, and Spain. We included participants aged 18 years and older diagnosed with Chagas disease with two different serological tests and detectable T cruzi DNA by qPCR in blood. Previously treated people, pregnant women, and people with severe cardiac forms were excluded. Participants were randomly assigned 1:1:1, using a balanced block randomisation scheme stratified by country, to receive benznidazole at three different doses: 300 mg/day for 60 days (control group), 150 mg/day for 60 days (low dose group), or 400 mg/day for 15 days (short treatment group). The primary outcome was the proportion of patients with a sustained parasitological negativity by qPCR during a follow-up period of 12 months. The primary safety outcome was the proportion of people who permanently discontinued the treatment. Both primary efficacy analysis and primary safety analysis were done in the intention-to-treat population. The trial is registered with EudraCT, 2016-003789-21, and ClinicalTrials.gov , NCT03191162 , and is completed. From April 20, 2017, to Sept 20, 2020, 245 people were enrolled, and 234 were randomly assigned: 78 to the control group, 77 to the low dose group, and 79 to the short treatment group. Sustained parasitological negativity was observed in 42 (54%) of 78 participants in the control group, 47 (61%) of 77 in the low dose group, and 46 (58%) of 79 in the short treatment group. Odds ratios were 1·41 (95% CI 0·69–2·88; p=0·34) when comparing the low dose and control groups and 1·23 (0·61–2·50; p=0·55) when comparing short treatment and control groups. 177 participants (76%) had an adverse event: 62 (79%) in the control group, 56 (73%) in the low dose group, and 59 (77%) in the short treatment group. However, discontinuations were less frequent in the short treatment group compared with the control group (2 [2%] vs 11 [14%]; OR 0·20, 95% CI 0·04–0·95; p=0·044). Participants had a similar parasitological responses. However, reducing the usual treatment from 8 weeks to 2 weeks might maintain the same response while facilitating adherence and increasing treatment coverage. These findings should be confirmed in a phase 3 clinical trial. European Community's 7th Framework Programme. [ABSTRACT FROM AUTHOR]

Enzymatic hydrolysis of corn stover was studied at agitation speeds from 50 to 500 rpm in a stirred tank bioreactor, at high solid concentrations (20% w/w dry solid/suspension), 50 °C and 15.5 mg protein ·g glucane −1 . Two empirical kinetic models have been fitted to empirical data, namely: a potential model and a fractal one. For the former case, the global order dramatically decreases from 13 to 2 as agitation speed increases, suggesting an increment in the access of enzymes to cellulose in terms of chemisorption followed by hydrolysis. For its part, the fractal kinetic model fits better to data, showing its kinetic constant a constant augmentation with increasing agitation speed up to a constant value at 250 rpm and above, when mass transfer limitations are overcome. In contrast, the fractal exponent decreases with rising agitation speed till circa 0.19, suggesting higher accessibility of enzymes to the substrate. [ABSTRACT FROM AUTHOR]

The effect of fluid dynamic conditions on enzymatic hydrolysis of acid pretreated corn stover (PCS) has been assessed. Runs were performed in stirred tanks at several stirrer speed values, under typical conditions of temperature (50 °C), pH (4.8) and solid charge (20% w/w). A complex mixture of cellulases, xylanases and mannanases was employed for PCS saccharification. At low stirring speeds (<150 rpm), estimated mass transfer coefficients and rates, when compared to chemical hydrolysis rates, lead to results that clearly show low mass transfer rates, being this phenomenon the controlling step of the overall process rate. However, for stirrer speed from 300 rpm upwards, the overall process rate is controlled by hydrolysis reactions. The ratio between mass transfer and overall chemical reaction rates changes with time depending on the conditions of each run. [ABSTRACT FROM AUTHOR]

Steam explosion and steam pre-treatment have proved capable of enhancing enzymatic saccharification of lignocellulosic materials. However, until now, these methods had not been compared under the same operational conditions and using the same raw material. Both pre-treatments lead to increased yields in the saccharification of Eucalyptus globulus; but results have been better with steam pre-treatments, despite the more accessible surface of exploded samples. The reason for this finding could be enzymatic inhibition: steam explosion causes a more extensive extraction of hemicelluloses and releases a greater amount of degradation products which can inhibit enzymatic action. Enzymatic inhibition is also dependent on the amount and chemical structure of lignin, which was also a contributing factor to the lower enzymatic yields obtained with the most severe pre-treatment. Thus, the highest yields (46.7% glucose and 73.4% xylose yields) were obtained after two cycle of steam treatment, of 5 and 3 min, at 183 °C. [ABSTRACT FROM AUTHOR]

• Enzymatic hydrolysis of three key lignocellulosic feedstocks is studied. • Fractal kinetic model fits well to all data from enzymatic hydrolysis runs. • Each feedstock, pretreatment and energy input reflect on the parameters values. • The pre-treatment severity correlates well with the fractal exponent parameters. Enzymatic hydrolysis of three pre-treated lignocellulosic biomasses –LCB- (wheat straw-WS-, corn stover-CSV- and cardoon stems –CS-) is studied. These biomasses were pre-treated by two methods: diluted sulfuric acid and acid ethanol-water extraction at six severity levels (H values). Pretreated solid fractions were hydrolyzed with commercial enzyme cocktails at standard conditions. A first-order kinetic fractal model was fitted to the experimental results. This model accurately describes the hydrolysis of all biomasses at all pre-treatment conditions studied. The results show that the formal first-order kinetic constant k depends on the biomass nature. The hydrolysis rate increases as the pre-treatment severity does, while the fractal exponent value h decreases. With these pre-treatments, and in terms of k and h, WS is highly reactive and, at medium H with EW pretreatment, highly accessible; CSV has a low reactivity and high accessibility and CS has the lowest reactivity and an increasing accessibility as severity rises. [ABSTRACT FROM AUTHOR]

Highlights • Wheat straw fractionation by ethanol-water treatment is made with re-used liquors. • The amount of reagent by re-using ethanol-water liquor is reduced, also the energy. • Re-used liquor has higher hydrolyzing ability than fresh liquor. Abstract Liquor recycle in lignocellulosic biomass fractionation with ethanol-water has been studied. Runs have been carried out in a 6 L tank reactor with liquor recirculation. The liquors obtained in six successive fractioning operations have been analyzed together with the solid phase remnant. Experimental results revealed that the number of re-uses reduces solids recovery (from 52.2 to 42.6%) and cellulose recovery (from 28.1 to 23.3%) with minor or no effect on the hemicelluloses and lignin removal. The more remarkable effect is an increase of the glucose yield (from 76.7 to 95.3% after enzymatic hydrolysis during 72 h). The accumulation of acetic acid in the spent liquors (until 1.3 g/L) seems to be responsible of the higher enzymatic hydrolysis yield, from 76.3 (first use) to 87.7% (fifth re-use). Liquor re-use is effective to improve the sustainability of the pre-treatment obtaining a cellulose-rich solid easy to hydrolysate to sugars reducing energy consumption. [ABSTRACT FROM AUTHOR]

Highlights • Results of pre-treatments are different depending on the raw material. • EW pre-treatment is more efficient to remove lignin than DSA pre-treatment. • DSA pre-treatment is better to hydrolysate xylans. • EW pre-treatment gives higher yields on glucose yield referred to initial raw material. • EW pre-treatment is more efficient than DSA pre-treatment especially at low-energy inputs. Abstract Ethanol-water (EW) and diluted sulfuric acid (DSA) pre-treatment have been studied for lignocellulosic biomass (corn stover, C ynara cardunculus L. stems and wheat straw). Both pre-treatments have been compared taken into account: solids recovery, glucans recovery, xylans removed, delignification and glucose yield. In all cases, the amount of energy involved has been taken as a criterion for sustainability. In general terms, EW is more efficient to remove lignin and DSA more appropriate to hydrolysate xylans. The combined effect of delignification and xylans removal is responsible for the improvement in the enzymatic cellulose hydrolysis. Under conditions of moderate-low energy inputs, EW pre-treatment yields better results than DSA with glucose yields in the range of 50–60% for EW pre-treated corn stover and cardoon stems; while wheat straw pulps reach up to 80%. So, multiple raw materials biorefinery needs a previous study to fit the type and conditions of the pre-treatment to each feedstock. [ABSTRACT FROM AUTHOR]

The fractionation of wheat straw by ethanol-water (EW) pre-treatment was studied regarding its main operating conditions: time, temperature, L/S ratio and ethanol percentage were optimized by using an orthogonal experimental design (Taguchi). Afterwards, diluted sulfuric acid (DSA) hydrolysis and EW treatments have been compared in terms of energy consumption and yield of a cellulosic solid residue able to be enzymatically hydrolyzed to glucose. Experimental results show that temperature is the only variable of EW with a significant effect on the quality of the pretreated solids. EW pre-treatment of wheat straw is more effective than DSA hydrolysis due to its higher capacity of delignification. Moreover, a high glucose yield (80%) can be obtained by enzymatic hydrolysis of a solid pretreated with a moderate energy input EW (160 °C, 45 min) while wheat straw needs of a higher energy input during DSA to produce a similar yield of glucose after saccharification. [ABSTRACT FROM AUTHOR]

Bacterial cellulose (BC) synthesized by Gluconacetobacter sucrofermentans CECT 7291 seems to be a good option for the restoration of degraded paper. In this work BC layers are cultivated and purified by two different methods: an alkaline treatment when the culture media contains ethanol and a thermal treatment if the media is free from ethanol. The main goal of these tests was the characterization of BC layers measured in terms of tear and burst indexes, optical properties, SEM, X-ray diffraction, FTIR, degree of polymerization, static and dynamic contact angles, and mercury intrusion porosimetry. The BC layers were also evaluated in the same terms after an aging treatment. Results showed that BC has got high crystallinity index, low internal porosity, good mechanical properties and high stability over time, especially when purified by the alkaline treatment. These features make BC an adequate candidate for degraded paper reinforcement. [ABSTRACT FROM AUTHOR]

Highlights: [•] Steam explosion and steam pre-treatments were carried out before kraft pulping. [•] The rate of extraction of hemicelluloses was similar with both pre-treatments. [•] Steam explosion enhanced delignification more efficiently. [•] Pre-treatments reduced paper mechanical properties owing to the fiber morphology. [•] Paper optical properties were boosted when pre-treatments were carried out. [Copyright &y& Elsevier]

Abstract: Chagas disease caused by Trypanosoma cruzi is a public health problem in Latin America. This parasite displays a high genetic diversity evidenced in six Discrete Typing Units (DTUs) namely TcI–TcVI. The aim of this study was to observe the temporal variation of the DTUs in asymptomatic patients at three different times (10 days interval). The results showed that intermittence is the rule in the bloodstream of Chagas disease patients. The patients showed different detectable DTUs with short time intervals, which favors the clonal histiotropic model and the multiclonality structure of this parasite. [Copyright &y& Elsevier]

Objectives: We conducted a systematic review and meta-analysis to determine if pre-operative brain natriuretic peptide (BNP) (i.e., BNP or N-terminal pro–B-type natriuretic peptide [NT-proBNP]) is an independent predictor of 30-day adverse cardiovascular outcomes after noncardiac surgery. Background: Pre-operative clinical cardiac risk indices have only modest predictive power. BNP predicts adverse cardiovascular outcomes in a variety of nonsurgical settings and may similarly predict these outcomes in the perioperative setting. Methods: We employed 5 search strategies (e.g., searching bibliographic databases), and we included all studies that assessed the independent prognostic value of pre-operative BNP measurement as a predictor of cardiovascular complications after noncardiac surgery. We determined study eligibility and conducted data abstraction independently and in duplicate. We calculated a pooled odds ratio using a random effects model. Results: Nine studies met eligibility criteria, and included a total of 3,281 patients, among whom 314 experienced 1 or more perioperative cardiovascular complications. The average proportion of patients with elevated BNP was 24.8% (95% confidence interval [CI]: 20.1 to 30.4%; I2 = 89%). All studies showed a statistically significant association between an elevated pre-operative BNP level and various cardiovascular outcomes (e.g., a composite of cardiac death and nonfatal myocardial infarction; atrial fibrillation). Data pooled from 7 studies demonstrated an odds ratio (OR) of 19.3 (95% CI: 8.5 to 43.7; I2 = 58%). The pre-operative BNP measurement was an independent predictor of perioperative cardiovascular events among studies that only considered the outcomes of death, cardiovascular death, or myocardial infarction (OR: 44.2, 95% CI: 7.6 to 257.0, I2 = 51.6%), and those that included other outcomes (OR: 14.7, 95% CI: 5.7 to 38.2, I2 = 62.2%); the p value for interaction was 0.28. Conclusions: These results suggest that an elevated pre-operative BNP or NT-proBNP measurement is a powerful, independent predictor of cardiovascular events in the first 30 days after noncardiac surgery. [Copyright &y& Elsevier]

Summary: A chemical genetics approach identified a cellular target of several proapoptotic farnesyl transferase inhibitors (FTIs). Treatment with these FTIs caused p53-independent apoptosis in Caenorhabditis elegans, which was mimicked by knockdown of endosomal trafficking proteins, including Rab5, Rab7, the HOPS complex, and notably the enzyme Rab geranylgeranyl transferase (RabGGT). These FTIs were found to inhibit mammalian RabGGT with potencies that correlated with their proapoptotic activity. Knockdown of RabGGT induced apoptosis in mammalian cancer cell lines, and both RabGGT subunits were overexpressed in several tumor tissues. These findings validate RabGGT, and by extension endosomal function, as a therapeutically relevant target for modulation of apoptosis, and enhance our understanding of the mechanism of action of FTIs. [Copyright &y& Elsevier]