Epicardial and endocardial surgical ablation of atrial fibrillation: outcomes from CASE-AF Registry.

OBJECTIVES: The German CArdioSurgEry Atrial Fibrillation Registry is a prospective, multicentric registry analysing outcomes of patients undergoing surgical ablation for atrial fibrillation as concomitant or stand-alone procedures. This data sub-analysis of the German CArdioSurgEry Atrial Fibrillation Registry aims to describe the in-hospital and 1-year outcomes after concomitant surgical ablation, based on 2 different ablation approaches, epicardial and endocardial surgical ablation. METHODS: Between January 2017 and April 2020, 17 German cardiosurgical units enrolled 763 consecutive patients after concomitant surgical ablation. In the epicardial group, 413 patients (54.1%), 95.6% underwent radiofrequency ablation. In the endocardial group, 350 patients (45.9%), 97.7% underwent cryoablation. 61.5% of patients in the epicardial group and 49.4% of patients in the endocardial group presenting with paroxysmal atrial fibrillation. Pre-, intra- and post-operative data were gathered. RESULTS: Upon discharge, 32.3% (n = 109) of patients after epicardial surgical ablation and 24.0% (n = 72) of patients after endocardial surgical ablation showed recurrence of atrial fibrillation. The in-hospital mortality rate was low, 2.2% (n = 9) in the epicardial and 2.9% (n = 10) in the endocardial group. The overall 1-year procedural success rate was 58.4% in the epicardial and 62.2% in the endocardial group, with significant symptom improvement in both groups. The 1-year mortality rate was 7.7% (n = 30) in epicardial and 5.0% (n = 17) in the endocardial group. CONCLUSIONS: Concomitant surgical ablation is safe and effective with significant improvement in patient symptoms and freedom from atrial fibrillation. Adequate cardiac rhythm monitoring should be prioritized for higher quality data acquisition.

Ferroptosis and PPAR-gamma in the limelight of brain tumors and edema.

Human malignant brain tumors such as gliomas are devastating due to the induction of cerebral edema and neurodegeneration. A major contributor to glioma-induced neurodegeneration has been identified as glutamate. Glutamate promotes cell growth and proliferation in variety of tumor types. Intriguently, glutamate is also an excitatory neurotransmitter and evokes neuronal cell death at high concentrations. Even though glutamate signaling at the receptor and its downstream effectors has been extensively investigated at the molecular level, there has been little insight into how glutamate enters the tumor microenvironment and impacts on metabolic equilibration until recently. Surprisingly, the 12 transmembrane spanning tranporter xCT (SLC7A11) appeared to be a major player in this process, mediating glutamate secretion and ferroptosis. Also, PPARγ is associated with ferroptosis in neurodegeneration, thereby destroying neurons and causing brain swelling. Although these data are intriguing, tumor-associated edema has so far been quoted as of vasogenic origin. Hence, glutamate and PPARγ biology in the process of glioma-induced brain swelling is conceptually challenging. By inhibiting xCT transporter or AMPA receptors in vivo, brain swelling and peritumoral alterations can be mitigated. This review sheds light on the role of glutamate in brain tumors presenting the conceptual challenge that xCT disruption causes ferroptosis activation in malignant brain tumors. Thus, interfering with glutamate takes center stage in forming the basis of a metabolic equilibration approach.

Production of Trichoderma harzianum K179 bioagent for maize diseases control: complete laboratory stage bioprocess development.

AIMS: In order to be competitive on the market, the production of biopreparations needs to be optimized, modelled, and assessed in the early stages of its development. The aim of this paper was to optimize medium for the production of Trichoderma harzianum K179 biocontrol agent, to analyze its kinetics at enlarged laboratory scale and finally economic analysis of the production of this high-value product through simulation modelling. METHODS AND RESULTS: The results showed that the bioprocess of T. harzianum K179 bioagent production in a laboratory bioreactor on the medium with optimal composition (dextrose 10 g l-1, soy flour 6.87 g l-1, K2HPO4 1.51 g l-1, KCl 0.5 g l-1, and MgSO4 × 7H2O 0.5 g l-1), at stirring speed of 1.75 × g and aeration intensity of 1.5 vvm, can be shortened from 96 to 36 h. The results of bioprocess economic analysis showed that with a 25-year project lifetime and an investment payback time of 7.58 years, this project represents an economically viable system. CONCLUSIONS: Complete analysis of the bioprocess of T. harzianum K179 biocontrol agent production showed that the biologically produced preparation can be competitive on the market with synthetic preparations.

Feasibility study of separation and purification of bile acid derivatives by HPLC on C18 and F5 columns.

Organic synthesis could be very demanding, usually due to difficulties related to the separation of main reaction products from by-products. Steroidal compounds could have similar lipophilicity, which is mostly based on the lipophilicity of the steroidal core. This causes many problems during purification, i.e. in obtaining a pure single steroidal compound. In this research, a group of bile acid derivatives were subjected to HPLC analysis using four experimental systems, which presented combinations of C18 and F5 columns with methanol-water and acetonitrile-water as mobile phases. Retention parameters and retention order of the compounds were established and indicated that all experimental systems could be applicable in order to separate and/or purify some individual compounds or a mixture of a few compounds. However, the only experimental system that could separate a mixture of all investigated derivatives proved to be a C18 column with acetonitrile-water as a mobile phase. Since complex interactions between F5 column and the analytes exist, molecular surface polarity (MSP) was tested as a lipophilicity parameter, and also compared with logP using multivariate statistics. Retention parameters obtained on F5 column were used as descriptors, both with MSP and with logP, concluding that logP has shown to be a better lipophilicity descriptor.

Utilization of waste glycerol for the production of biocontrol agents nigericin and niphimycin by Streptomyces hygroscopicus: bioprocess development.

Search for more environment-friendly methods for controlling plant diseases that would contribute to the goal of sustainability in agriculture is in focus. In the present study, the potential of Streptomyces hygroscopicus isolated from soil sample in the production of biocontrol agents, nigericin and niphimycin, effective against Alternaria alternata storage apple pathogen was examined. Also, modelling and optimization of medium composition for biocontrol agent biosynthesis was performed. The results showed that the optimum amount of C3H8O3, (NH4)2SO4 and K2HPO4 in the medium for Streptomyces hygroscopicus biosynthesis is 20, 0.25 and 1.46 g/L, respectively. Scale-up and validation of the obtained results performed in the 3 L laboratory-scale bioreactor showed that on the optimized medium at an aeration rate of 0.7 vvm and an agitation speed of 200 rpm, produced nigericin and niphimycin, showed high activity. Under the same conditions, cultivation of S. hygroscopicus was performed in a 7 L laboratory bioreactor in a medium with waste glycerol instead of pure glycerol. Results showed that the methanol extract of S. hygroscopicus cultivation liquid, containing nigericin and niphimycin, was high effective against two Alternaria isolates. This was confirmed in vitro by obtaining large inhibition zone diameters on A. alternata KA10 (47 mm) and T1Jg3 (44.33 mm) isolates. After successful in vitro analysis, in planta testing was performed. It was found that necrosis diameters that were measured on artificially inoculated apple fruits with A. alternata compared to necrosis diameter measured on untreated, control fruits, were 4.47 and 3.56 times smaller.

Optimization of glycerol-based medium composition for antifungal metabolites production by Bacillus subtilis

Abstract Bacillus species are promising producers of various compounds that have pronounced antimicrobial, antiviral and antitumor activities. Due to its GRAS status, Bacillus subtilis represents an excellent candidate for the usage in plant pathogens biocontrol. In this research, evaluation of antifungal metabolites biosynthesis by Bacillus subtilis ATCC 6633 and optimization of glycerol-based medium composition, using response surface methodology, for the production of compounds effective against Neurospora crassa were investigated. The results of disc-diffusion method indicate that applied Bacillus strain produces compounds with antifungal activity against tested fungus. In order to find optimal cultivation medium composition, the experiments were carried out in accordance with Box-Behnken design, and optimization was performed using the concept of desirability function combined with previously defined mathematical equation, which describes examined bioprocess. The optimization model predicts that maximum inhibition zone diameter against Neurospora crassa of 32.24 mm is achieved when initial content of glycerol, NaNO2 and K2HPO4 were 49.68 g/L, 2.90 g/L and 6.49 g/L, respectively. Additionally, the second optimization set was made to minimize the consumption of medium components and costs of medium preparation. The obtained results are the basis for further research aimed to develop medium appropriate for economically justified production of bioactive compounds at industrial scale.