Aims
Atrial fibrillation (AF) worsens the prognosis of patients with heart failure (HF). Successful treatments are still very scarce for those with permanent AF and preserved (HFpEF) or mildly ...reduced (HFmrEF) ejection fraction. In this study, the long‐term benefits and safety profile of heart rate regularization through left‐bundle branch pacing (LBBP) and atrioventricular node ablation (AVNA) will be explored in comparison with pharmacological rate‐control strategy.
Methods and results
The PACE‐FIB trial is a multicentre, prospective, open‐label, randomized (1:1) clinical study that will take place between March 2022 and February 2027. A total of 334 patients with HFpEF/HFmrEF and permanent AF will receive either LBBP followed by AVNA (intervention arm) or optimal pharmacological treatment for heart rate control according to European guideline recommendations (control arm). All patients will be followed up for a minimum of 36 months. The primary outcome measure will be the composite of all‐cause mortality, HF hospitalization, and worsening HF at 36 months. Other secondary efficacy and safety outcome measures such as echocardiographic parameters, functional status, and treatment‐related adverse events, among others, will be analysed too.
Conclusion
LBBP is a promising stimulation mode that may foster the clinical benefit of heart rate regularization through AV node ablation compared with pharmacological rate control. This is the first randomized trial specifically addressing the long‐term efficacy and safety of this pace‐and‐ablate strategy in patients with HFpEF/HFmrEF and permanent AF.
The molecule (2
)-naringenin is a scaffold molecule with several nutraceutical properties. Currently, (2
)-naringenin is obtained through chemical synthesis and plant isolation. However, these ...methods have several drawbacks. Thus, heterologous biosynthesis has emerged as a viable alternative to its production. Recently, (2
)-naringenin production studies in
have used different tools to increase its yield up to 588 mg/L. In this study, we designed and assembled a bio-factory for (2
)-naringenin production. Firstly, we used several parametrized algorithms to identify the shortest pathway for producing (2
)-naringenin in
, selecting the genes phenylalanine ammonia lipase (
), 4-coumarate: CoA ligase (
), chalcone synthase (
), and chalcone isomerase (
) for the biosynthetic pathway. Then, we evaluated the effect of oxygen transfer on the production of (2
)-naringenin at flask (50 mL) and bench (4 L culture) scales. At the flask scale, the agitation rate varied between 50 rpm and 250 rpm. At the bench scale, the dissolved oxygen was kept constant at 5% DO (dissolved oxygen) and 40% DO, obtaining the highest (2
)-naringenin titer (3.11 ± 0.14 g/L). Using genome-scale modeling, gene expression analysis (RT-qPCR) of oxygen-sensitive genes was obtained.
Native Mexican plants are a wide source of bioactive compounds such as pentacyclic triterpenes. Pentacyclic triterpenes biosynthesized through the mevalonate (MVA) and the ...2-C-methyl-D-erythritol-phosphate (MEP) metabolic pathways are highlighted by their diverse biological activity. Compounds belonging to the oleanane, ursane, and lupane groups have been identified in about 33 Mexican plants, located geographically in the southwest of Mexico. The works addressing these findings have reported 45 compounds that mainly show antimicrobial activity, followed by anti-inflammatory, cytotoxic, anxiolytic, hypoglycemic, and growth-stimulating or allelopathic activities. Extraction by maceration and Soxhlet with organic solvents and consecutive chromatography of silica gel have been used for their whole or partial purification. Nanoparticles and nanoemulsions are the vehicles used in Mexican formulations for drug delivery of the pentacyclic triterpenes until now. Sustainable extraction, formulation, regulation, isolation, characterization, and bioassay facilities are areas of opportunity in pentacyclic triterpenes research in Mexico while the presence of plant and human resources and traditional knowledge are strengths. The present review discusses the generalities of the pentacyclic triterpene (definition, biogenic classification, and biosynthesis), a summary of the last two decades of research on the compounds identified and their evaluated bioactivity, the generalities about the extraction and purification methods used, drug delivery aspects, and a critical analysis of the advantages and limitations of research carried out in this way.
Flavonoids are a group of compounds generally produced by plants with proven biological activity, which have recently beeen recommended for the treatment and prevention of diseases and ailments with ...diverse causes. In this study, naringenin was produced in adequate amounts in yeast after
design. The four genes of the involved enzymes from several organisms (bacteria and plants) were multi-expressed in two vectors carrying each two genes linked by a short viral peptide sequence. The batch kinetic behavior of the product, substrate, and biomass was described at lab scale. The engineered strain might be used in a more affordable and viable bioprocess for industrial naringenin procurement.
Introduction and Objectives
Pulmonary congestion (PC) is associated with an increased risk of hospitalization and death in patients with heart failure (HF). Lung ultrasound has shown to be highly ...sensitive for detecting PC in HF. The aim of this study is to evaluate whether lung ultrasound–guided therapy improves 6-month outcomes in patients with HF compared with conventional treatment.
Materials and Methods
Randomized, multicenter, single-blind clinical trial in patients discharged from Internal Medicine Departments after hospitalization for decompensated HF. Participants will be assigned 1:1 to receive treatment guided according to the presence of lung ultrasound signs of congestion (semi-quantitative evaluation of B lines and the presence of pleural effusion) versus clinical assessment of congestion. The primary outcome is the combination of cardiovascular death and readmission for HF at 6 months.
Conclusions
The results of this study will provide more evidence about the impact of lung ultrasound on treatment monitoring in patients with chronic HF.
Hereditary hemorrhagic telangiectasia is an inherited disease related to an alteration in angiogenesis, manifesting as cutaneous telangiectasias and epistaxis. As complications, it presents vascular ...malformations in organs such as the lung, liver, digestive tract, and brain. Currently, diagnosis can be made using the Curaçao criteria or by identifying the affected gene. In recent years, there has been an advance in the understanding of the pathophysiology of the disease, which has allowed the use of new therapeutic strategies to improve the quality of life of patients. This article reviews some of the main and most current evidence on the pathophysiology, clinical manifestations, diagnostic approach, screening for complications, and therapeutic options, both pharmacological and surgical.
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