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Background: Enhanced characterization of the atrial electrical substrate may lead to better comprehension of atrial fibrillation (AF) pathophysiology., Objective: With the use of high-density substrate mapping, we sought to investigate the occurrence of functional electrophysiologic phenomena in the left atrium and to assess potential association with arrhythmia recurrences after catheter ablation., Methods: Sixty-three consecutive patients with AF referred for ablation were enrolled. Analysis of conduction abnormalities relied on 2 acquired left atrial electroanatomic maps (sinus and atrial paced rhythm). We classified conduction abnormalities as fixed (if these were present in both rhythms) or functional rhythm dependent (if unmasked in 1 of the 2 rhythms). Esophagus and aorta locations were recorded to check the correspondence with abnormal conduction sites., Results: There were 234 conduction abnormalities detected, of which 125 (53.4%) were functional rhythm dependent. The most frequent anatomic site of functional phenomena was the anterior wall, followed by the posterior wall, in sinus rhythm and the pulmonary venous antra in paced rhythm. Sites of functional phenomena in 82.6% of cases corresponded with extracardiac structures, such as sinus of Valsalva of ascending aorta anteriorly and the esophagus posteriorly. Most (88%) areas with functional phenomena had normal bipolar voltage. After pulmonary vein ablation, the number of residual functional phenomena is an independent predictor of AF recurrence (hazard ratio, 2.539 [1.458-4.420]; P = .001) with a risk of recurrences at multivariable Cox analysis., Conclusion: Dual high-density mapping (during sinus and paced rhythms) is able to unmask functional, rhythm-dependent phenomena that are predictive of AF recurrences during follow-up., Competing Interests: Disclosures Dr Frontera has received speaker fees from Biosense Webster. Francesca Comi is an employee at Biosense Webster. All other authors have reported that they have no relationships relevant to the contents of this manuscript to disclose., (Copyright © 2024 Heart Rhythm Society. All rights reserved.)

The continuous release of municipal and industrial products into the environment poses a growing concern for public health. Among environmental pollutants, polystyrene (PS) stands out as a primary constituent of environmental plastic waste, given its widespread use and high production rates owing to its durability and user-friendly properties. The detection of polystyrene microparticles (PS-MPs) in various living organisms has been well-documented, posing a serious threat due to their potential passage into the human ecosystem. In this manuscript, we aimed to study the toxicological effects of low concentrations of pristine and photoaged PS-MPs in a murine macrophage cell line. To this purpose, PS-MPs were photoaged by indoor exposure to visible light to simulate environmental weathering due to solar irradiation (PS-MPs 3h ). Physical characterization revealed that the irradiation treatment results in particle degradation and the possible release of nanoparticles. Monocultures of the RAW264.7 cell line were then exposed to PS-MPs and PS-MPs 3h at concentrations comparable to experimental measurements from biological samples, to assess cytotoxicity, intracellular oxidative stress, primary genotoxicity, and inflammatory effects. Significant toxicity-related outcomes were observed in cells treated with both pristine PS-MPs and PS-MPs 3h even at low concentrations (0,10 μg/ml and 1 μg/ml). PS-MPs 3h exhibited greater adverse effects compared to PS-MPs, including reduced cell viability, increased ROS production, elevated DNA damage, and upregulation of IL-6 and NOS2 gene expression. Therefore, we can conclude that changes induced by environmental aging in the physicochemical composition of PS microplastics play a crucial role in the adverse health outcomes associated with microplastic exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hepatocellular carcinoma (HCC) is a common cancer which unfortunately has poor outcomes. Common anti-cancer treatments such as chemotherapy and targeted therapy have not increased patient survival significantly. A common treatment for HCC patients is transplantation, however, it has limitations and complications. Novel approaches are necessary to more effectively treat HCC patients. Berberine (BBR) is a nutraceutical derived from various fruits and trees, which has been used for centuries in traditional medicine to treat various diseases such as diabetes and inflammation. More recently, the anti-proliferation effects of BBR have been investigated in the treatment of patients with various cancers, especially colorectal cancer, and in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). In this review, we will focus on studies with BBR in liver diseases., Competing Interests: Declaration of competing interest The authors declare that there are no competing financial interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. It is a major public health problem worldwide, and it is often diagnosed at advanced stages, when no effective treatment options are available. Extracellular vesicles (EVs) are nanosized double-layer lipid vesicles containing various biomolecule cargoes, such as lipids, proteins, and nucleic acids. EVs are released from nearly all types of cells and have been shown to play an important role in cell-to-cell communication. In recent years, many studies have investigated the role of EVs in cancer, including HCC. Emerging studies have shown that EVs play primary roles in the development and progression of cancer, modulating tumor growth and metastasis formation. Moreover, it has been observed that non-coding RNAs (ncRNAs) carried by tumor cell-derived EVs promote tumorigenesis, regulating the tumor microenvironment (TME) and playing critical roles in the progression, angiogenesis, metastasis, immune escape, and drug resistance of HCC. EV-related ncRNAs can provide information regarding disease status, thus encompassing a role as biomarkers. In this review, we discuss the main roles of ncRNAs present in HCC-derived EVs, including micro(mi) RNAs, long non-coding (lnc) RNAs, and circular (circ) RNAs, and their potential clinical value as biomarkers and therapeutic targets., Competing Interests: The authors declare no conflicts of interest.

The identification of biomarkers for predicting inter-individual sorafenib response variability could allow hepatocellular carcinoma (HCC) patient stratification. SNPs in angiogenesis- and drug absorption, distribution, metabolism, and excretion (ADME)-related genes were evaluated to identify new potential predictive biomarkers of sorafenib response in HCC patients. Five known SNPs in angiogenesis-related genes, including VEGF-A , VEGF-C , HIF-1a , ANGPT2 , and NOS3 , were investigated in 34 HCC patients (9 sorafenib responders and 25 non-responders). A subgroup of 23 patients was genotyped for SNPs in ADME genes. A machine learning classifier method was used to discover classification rules for our dataset. We found that only the VEGF-A (rs2010963) C allele and CC genotype were significantly associated with sorafenib response. ADME-related gene analysis identified 10 polymorphic variants in ADH1A (rs6811453), ADH6 (rs10008281), SULT1A2/CCDC101 (rs11401), CYP26A1 (rs7905939), DPYD (rs2297595 and rs1801265), FMO2 (rs2020863), and SLC22A14 (rs149738, rs171248, and rs183574) significantly associated with sorafenib response. We have identified a genetic signature of predictive response that could permit non-responder/responder patient stratification. Angiogenesis- and ADME-related genes correlation was confirmed by cumulative genetic risk score and network and pathway enrichment analysis. Our findings provide a proof of concept that needs further validation in follow-up studies for HCC patient stratification for sorafenib prescription.