NLRP3 cages revealed by full-length mouse NLRP3 structure control pathway activation.

The NACHT-, leucine-rich-repeat- (LRR), and pyrin domain-containing protein 3 (NLRP3) is emerging to be a critical intracellular inflammasome sensor of membrane integrity and a highly important clinical target against chronic inflammation. Here, we report that an endogenous, stimulus-responsive form of full-length mouse NLRP3 is a 12- to 16-mer double-ring cage held together by LRR-LRR interactions with the pyrin domains shielded within the assembly to avoid premature activation. Surprisingly, this NLRP3 form is predominantly membrane localized, which is consistent with previously noted localization of NLRP3 at various membrane organelles.

Extraction and Encapsulation of Phenolic Compounds of Tunisian Rosemary ( L.) Extracts in Silk Fibroin Nanoparticles.

Rosemary ( L.) is known to be an effective potential source of natural antioxidants which confer benefits to human health. Their bioactive properties are mainly due to phenolic compounds but these molecules are highly vulnerable to oxidants, light, heat, pH, water and enzymatic activities.

Antithrombotic therapy and clinical outcomes at 1 year in the Spanish cohort of the EORP-AF Long-term General Registry.

Background: Atrial fibrillation (AF) increases the risk of thromboembolism. We investigate the efficacy and safety of oral anticoagulation (OAC) therapy and explored the number needed to treat for net effect (NNTnet) of OAC in the Spanish cohort of the EURObservational Research Programme-AF (EORP-AF) Long-term General Registry.

Methods: The EORP-AF General Registry is a prospective, multicentre registry conducted in ESC countries, including consecutive AF patients.

Genome Profiling of H3k4me3 Histone Modification in Human Adipose Tissue during Obesity and Insulin Resistance.

Background: Adipose tissue (AT) dysfunction is involved in obesity-related comorbidities. Epigenetic alterations have been recently associated with AT deterioration in obesity conditions. In this work, we profiled the H3K4me3 histone mark in human AT, with special emphasis on the changes in the pattern of histone modification in obesity and insulin resistance (IR).

First Description of Late-Onset Autoinflammatory Disease Due to Somatic NLRC4 Mosaicism.

Objective: Autoinflammatory diseases are inherited disorders of innate immunity that usually start during childhood. However, several recent reports have described an increasing number of patients with autoinflammatory disease starting in adulthood. This study was undertaken to investigate the underlying cause of a case of late-onset uncharacterized autoinflammatory disease.

Natural Coumarins: Exploring the Pharmacological Complexity and Underlying Molecular Mechanisms.

Coumarins belong to the benzopyrone family commonly found in many medicinal plants. Natural coumarins demonstrated a wide spectrum of pharmacological activities, including anti-inflammatory, anticoagulant, anticancer, antibacterial, antimalarial, casein kinase-2 (CK2) inhibitory, antifungal, antiviral, Alzheimer's disease inhibition, neuroprotective, anticonvulsant, phytoalexins, ulcerogenic, and antihypertensive. There are very few studies on the bioavailability of coumarins; therefore, further investigations are necessitated to study the bioavailability of different coumarins which already showed good biological activities in previous studies.

Sensing low intracellular potassium by NLRP3 results in a stable open structure that promotes inflammasome activation.

The NLRP3 inflammasome is activated by a wide range of stimuli and drives diverse inflammatory diseases. The decrease of intracellular K concentration is a minimal upstream signal to most of the NLRP3 activation models. Here, we found that cellular K efflux induces a stable structural change in the inactive NLRP3, promoting an open conformation as a step preceding activation.

Efficacy and safety of direct-acting oral anticoagulants compared to vitamin K antagonists in COVID-19 outpatients with cardiometabolic diseases.

Background: It remains uncertain if prior use of oral anticoagulants (OACs) in COVID-19 outpatients with multimorbidity impacts prognosis, especially if cardiometabolic diseases are present. Clinical outcomes 30-days after COVID-19 diagnosis were compared between outpatients with cardiometabolic disease receiving vitamin K antagonist (VKA) or direct-acting OAC (DOAC) therapy at time of COVID-19 diagnosis.

Methods: A study was conducted using TriNetX, a global federated health research network.

Characterization of atrial fibrillation in real-world patients: testing the 4S-AF scheme in the Spanish and French cohorts of the EORP-AF Long-Term General Registry.

Aims: The 4S-AF scheme [Stroke risk, Symptom severity, Severity of atrial fibrillation (AF) burden, Substrate severity] has recently been described as a novel approach to in-depth characterization of AF. We aim to determine if the 4S-AF scheme would be useful for AF characterization and provides prognostic information in real-world AF patients.

Methods And Results: The Spanish and French cohorts of the EORP-AF Long-Term General Registry were included.

Silk fibroin nanoparticles enhance quercetin immunomodulatory properties in DSS-induced mouse colitis.

Inflammatory bowel disease (IBD) is a chronic and idiopathic inflammatory disorder affecting the gastrointestinal tract. The pharmacological treatments used currently for its treatment lack efficacy, so new therapeutic strategies should be developed. In this context, flavonoids loaded in biopolymeric nanoparticles can be considered as novel promising candidates.

Relationship between multimorbidity and outcomes in atrial fibrillation.

Background: Multimorbidity is common in atrial fibrillation (AF) patients. Charlson comorbidity index (CCI) is used to evaluate multimorbidity in the general population. Limited long-term data are available on the relationship between CCI and AF.

Antithrombotic Therapy in Patients with Peripheral Artery Disease: A Focused Review on Oral Anticoagulation.

Peripheral artery disease (PAD) is a major cause of morbidity and mortality but it is usually underdiagnosed and undertreated. Patients with PAD present dysregulated procoagulant, anticoagulant, and fibrinolytic pathways leading to arterial and venous thrombosis. The risk of several ischemic-related complications could be mitigated with appropriate antithrombotic therapy, which plays a central role in all types of PAD.

Direct-acting oral anticoagulants use prior to COVID-19 diagnosis and associations with 30-day clinical outcomes.

Background: It is unclear if direct-acting oral anticoagulants (DOACs) use before hospitalization due to COVID-19 diagnosis would potentially impact the severity and clinical outcomes thereafter. We compared 30-day hospitalization/re-hospitalization and clinical outcomes between patients on chronic DOAC therapy and patients not on oral anticoagulation (OAC) therapy at time of COVID-19 diagnosis.

Methods: We used data from TriNetX, a global federated health research network.

Number needed to treat for net effect of anticoagulation in atrial fibrillation: Real-world vs. clinical-trial evidence.

Aims: The net benefit of oral anticoagulants (OACs) in atrial fibrillation (AF) is poorly understood. We aimed to determine the NNT for net effect (NNT ) using calculator of absolute stroke risk (CARS) in anticoagulated patients with AF in real-world and clinical trial cohorts.

Methods: Post-hoc analysis of patient-level data from the real-world Murcia AF Project and AMADEUS clinical trial.

Mid-term outcomes of rapid deployment aortic prostheses in patients with small aortic annulus.

Objectives: The Edwards Intuity valve is a rapid deployment aortic prosthesis that favours less invasive approaches. However, evidence about the clinical behaviour of their smaller sizes is scarce. Herein, we studied haemodynamic behaviours and clinical outcomes of small Intuity prostheses (19-21 mm) in comparison to larger Intuity prostheses (>21 mm).

Distinctive Biomarker Features in the Endotheliopathy of COVID-19 and Septic Syndromes.

Background: Endotheliopathy is a key element in COVID-19 pathophysiology, contributing to both morbidity and mortality. Biomarkers distinguishing different COVID-19 phenotypes from sepsis syndrome remain poorly understood.

Objective: To characterize circulating biomarkers of endothelial damage in different COVID-19 clinical disease stages compared with sepsis syndrome and normal volunteers.

Relationship between sleep habits and academic performance in university Nursing students.

Background: Sleep disorders are composed of a group of diseases of increasing prevalence and with social-health implications to be considered a public health problem. Sleep habits and specific sleep behaviors have an influence on the academic success of students. However, the characteristics of sleep and sleep habits of university students as predictors of poor academic performance have been scarcely analyzed.

Variables affecting the quality of anticoagulation in atrial fibrillation patients newly initiating vitamin K antagonists: insights from the national and multicentre SULTAN registry.

Aims: Vitamin K antagonists (VKAs) are effective drugs reducing the risk for stroke in atrial fibrillation (AF), but the benefits derived from such therapy depend on the international normalized ratio (INR) maintenance in a narrow therapeutic range. Here, we aimed to determine independent variables driving poor anticoagulation control [defined as a time in therapeutic range (TTR) <65%] in a 'real world' national cohort of AF patients.

Methods And Results: The SULTAN registry is a multicentre, prospective study, involving patients with non-valvular AF from 72 cardiology units expert in AF in Spain.

Disparity between central and peripheral refraction inheritance in twins.

The last decades have witnessed a sudden increase in myopia incidence among youngsters that have been related to modern lifestyle along with the use of emerging technologies affecting visual exposure. Increasing exposures to known risk factors for myopia, such as time spent indoors, close-distance work, or low-light conditions are thought to be responsible for this public health issue. In most cases, development of myopia is secondary to a vitreous chamber enlargement, although the related mechanisms and the potential interaction between central and peripheral retinal area remain unclear.

Cardiovascular risk factors, cardiovascular disease, and COVID-19: an umbrella review of systematic reviews.

Aims: To consolidate evidence to determine (i) the association between cardiovascular risk factors and health outcomes with coronavirus 2019 (COVID-19); and (ii) the impact of COVID-19 on cardiovascular health.

Methods And Results: An umbrella review of systematic reviews was conducted. Fourteen medical databases and pre-print servers were searched from 1 January 2020 to 5 November 2020.

Adherence to the 'Atrial Fibrillation Better Care' Pathway in Patients with Atrial Fibrillation: Impact on Clinical Outcomes-A Systematic Review and Meta-Analysis of 285,000 Patients.

Objective: The 'Atrial fibrillation Better Care' (ABC) pathway has been recently proposed as a holistic approach for the comprehensive management of patients with atrial fibrillation (AF). We performed a systematic review of current evidence for the use of the ABC pathway on clinical outcomes.

Methods And Results: We performed a systematic review and meta-analysis according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.

Validating scores predicting atrial fibrillation recurrence post catheter ablation in patients with concurrent atrial fibrillation and pulmonary diseases.

Background: Several scores were available for predicting atrial fibrillation (AF) recurrence post radiofrequency ablation. However, the role of different scores predicting AF recurrence after ablation in patients with concurrent AF and pulmonary diseases (PDs) remained obscure. Herein, we aimed to investigate their predicting values and differences in patients with concurrent AF and PDs.

Telomerase reverse transcriptase activates transcription of miR500A to inhibit Hedgehog signalling and promote cell invasiveness.

Telomerase reverse transcriptase (TERT) maintains telomere homeostasis, thus ensuring chromosome stability and cell proliferation. In addition, several telomere-independent functions of human TERT have been described. In this study, we report that TERT binds directly to the TCF binding elements located upstream of the oncomiR miR500A, and induces its transcription.