Segmental Versus Circumferential Ablation of Pulmonary Veins in Patients with Paroxysmal Atrial Fibrillation

INTRODUCTION: Pulmonary vein isolation (PVI) is the cornerstone of catheter ablation techniques for the treatment of paroxysmal atrial fibrillation (PAF), with significantly improved efficacy compared to antiarrhythmic drugs as shown in CABANA trial. However, the question arises in which PAF patients whether the procedure can be limited to PVs only showing potentials (segmental), or it is really necessary to isolate all PV (circumferential). Even though success rates for circumferential PV ablation (CPVA) have been reported to be higher (up to 90%), than segmental PV ablation, most CPVA procedures previously reported included left atrial linear ablation, additional ablation lesions or lines connecting the mitral valve to the posterior PVs or along the roof of the left atrium which made bias to these studies. AIM: Thus, we initiated this randomized controlled study to evaluate the efficacy of CPVA versus SPVI in subjects undergoing ablation of PAF. METHODS: Our study included 31 consecutive patients who underwent their first radiofrequency ablation for PAF between March 2015 and March 2017. Patients were randomized for circumferential or segmental ablation on the day of the procedure. We had two groups, circumferential (17 patients) and segmental group (14 patients). RESULTS: There was no difference between two groups on our primary endpoint, the recurrence, which was 2 out of 14 patients (14.3%) in the segmental ablation group, compared to 3 out of 17 patients (17.6%) who were circumferential ablated. This difference is statistically insignificant (p = 1). For other endpoints, there was also no statistically significant difference between circumferential and segmental regarding fluoroscopy time, 53.47 ± 8.7 min versus 54.93 ± 15.02 min, p = 0.738, procedure time, 184.18 ±19.28 min versus 191.43 ± 20 min p = 0.315, and even for radio frequency time which was lower in segmental group but did not differ statistically, 35.71 ± 5.73 min versus 34.79 ± 5.29, min p = 0.649. CONCLUSION: The previous studies showed the superiority of circumferential PVI on segmental strategy regarding effectiveness, but in those studies, linear ablations were added to circumferential strategy and done in cases of persistent and PAF. In our randomized study, we compared between two methods in cases of PAF, which showed that segmental ablation is not inferior to circumferential ablation of PVI

Totalna kordektomija u pacijenta s primarnim dorzolumbarnim multiformnim glioblastomom i paraplegijom – prikaz slučaja

In this paper, we report a case of a 57-year-old male patient with non-metastatic dorso-lumbar glioblastoma multiforme (GBM) who underwent total cordectomy followed by chemoradiotherapy. Primary dorso-lumbar GBM is a rare finding. Despite the total cordectomy and chemoradiotherapy treatment, recurrence occurs mostly within a short time with poor prognosis.Muškarac u dobi od 57 godina s nemetastatskim multiformnim dorzolumbalnim glioblastomom (GBM) podvrgnut je totalnoj kordektomiji i kemoradioterapiji. Primarni dorzolumbalni GBM se rijetko nalazi. Unatoč totalnoj kordektomiji i kemoradioterapiji bolest se vraća s lošom prognozom u kratkom vremenskom razdoblju

Modulation of preeclampsia by the cholinergic anti-inflammatory pathway: Therapeutic perspectives

The cholinergic anti-inflammatory pathway (CAP) is vital for the orchestration of the immune and inflammatory responses under normal and challenged conditions. Over the past two decades, peripheral and central circuits of CAP have been shown to be critically involved in dampening the inflammatory reaction in a wide array of inflammatory disorders. Additionally, emerging evidence supports a key role for CAP in the regulation of the female reproductive system during gestation as well as in the advent of serious pregnancy-related inflammatory insults such as preeclampsia (PE). Within this framework, the modulatory action of CAP encompasses the perinatal maternal and fetal adverse consequences that surface due to antenatal PE programming. Albeit, a considerable gap still exists in our knowledge of the precise cellular and molecular underpinnings of PE/CAP interaction, which hampered global efforts in safeguarding effective preventive or therapeutic measures against PE complications. Here, we summarize reports in the literature regarding the roles of peripheral and reflex cholinergic neuroinflammatory pathways of nicotinic acetylcholine receptors (nAChRs) in reprogramming PE complications in mothers and their progenies. The possible contributions of α7-nAChRs, cholinesterases, immune cells, adhesion molecules, angiogenesis, and endothelial dysfunction to the interaction have also been reviewed.Supported by the Science and Technology Development Fund, Egypt (STDF Grant No. 14895)

Promising biotherapeutic prospects of different probiotics and their derived postbiotic metabolites: in-vitro and histopathological investigation

Abstract Background Probiotics and their derived postbiotics, as cell-free supernatants (CFS), are gaining a solid reputation owing to their prodigious health-promoting effects. Probiotics play a valuable role in the alleviation of various diseases among which are infectious diseases and inflammatory disorders. In this study, three probiotic strains, Lactiplantibacillus plantarum, Lacticaseibacillus rhamnosus, and Pediococcus acidilactici, were isolated from marketed dietary supplements. The antimicrobial activity of the isolated probiotic strains as well as their CFS was investigated. The neutralized CFS of the isolated probiotics were tested for their antibiofilm potential. The anti-inflammatory activity of the isolated Lactobacillus spp., together with their CFS, was studied in the carrageenan-induced rat paw edema model in male Wistar rats. To the best of our knowledge, such a model was not previously experimented to evaluate the anti-inflammatory activity of the CFS of probiotics. The histopathological investigation was implemented to assess the anti-inflammatory prospect of the isolated L. plantarum and L. rhamnosus strains as well as their CFS. Results The whole viable probiotics and their CFS showed variable growth inhibition of the tested indicator strains using the agar overlay method and the microtiter plate assay, respectively. When tested for virulence factors, the probiotic strains were non-hemolytic lacking both deoxyribonuclease and gelatinase enzymes. However, five antibiotic resistance genes, blaZ, ermB, aac(6’)- aph(2”), aph(3’’)-III, and vanX, were detected in all isolates. The neutralized CFS of the isolated probiotics exhibited an antibiofilm effect as assessed by the crystal violet assay. This effect was manifested by hindering the biofilm formation of the tested Staphylococcus aureus and Pseudomonas aeruginosa clinical isolates in addition to P. aeruginosa PAO1 strain. Generally, the cell cultures of the two tested probiotics moderately suppressed the acute inflammation induced by carrageenan compared to indomethacin. Additionally, the studied CFS relatively reduced the inflammatory changes compared to the inflammation control group but less than that observed in the case of the probiotic cultures treated groups. Conclusions The tested probiotics, along with their CFS, showed promising antimicrobial and anti-inflammatory activities. Thus, their safety and their potential use as biotherapeutics for bacterial infections and inflammatory conditions are worthy of further investigation

IUPHAR ECR review: The cGAS-STING pathway: Novel functions beyond innate immune and emerging therapeutic opportunities

Stimulator of interferon genes (STING) is a crucial innate immune sensor responsible for distinguishing pathogens and cytosolic DNA, mediating innate immune signaling pathways to defend the host. Recent studies have revealed additional regulatory functions of STING beyond its innate immune-related activities, including the regulation of cellular metabolism, DNA repair, cellular senescence, autophagy and various cell deaths. These findings highlight the broader implications of STING in cellular physiology beyond its role in innate immunity. Currently, approximately 10 STING agonists have entered the clinical stage. Unlike inhibitors, which have a maximum inhibition limit, agonists have the potential for infinite amplification. STING signaling is a complex process that requires precise regulation of STING to ensure balanced immune responses and prevent detrimental autoinflammation. Recent research on the structural mechanism of STING autoinhibition and its negative regulation by adaptor protein complex 1 (AP-1) provides valuable insights into its different effects under physiological and pathological conditions, offering a new perspective for developing immune regulatory drugs. Herein, we present a comprehensive overview of the regulatory functions and molecular mechanisms of STING beyond innate immune regulation, along with updated details of its structural mechanisms. We discuss the implications of these complex regulations in various diseases, emphasizing the importance and feasibility of targeting the immunity-dependent or immunity-independent functions of STING. Moreover, we highlight the current trend in drug development and key points for clinical research, basic research, and translational research related to STING

Scar identification, quantification, and characterization in complex atrial tachycardia: A path to targeted ablation?

Successful catheter ablation of scar-related atrial tachycardia depends on correct identification of the critical isthmus. Often, this is a represented by a small bundle of viable conducting tissue within a low-voltage area. It's identification depends on the magnitude of the signal/noise ratio. Ultra-high density mapping, multipolar catheters with small (eventually unidirectional) and closely-spaced electrodes improves low-voltage electrogram detection. Background noise limitation is also of major importance for improving the signal/noise ratio. Electrophysiological properties of the critical isthmus and the characteristics of the local bipolar electrograms have been recently demonstrated as hallmarks of successful ablation sites in the setting of scar-related atrial tachycardia.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Supplementary Figures 1-8 from FOXA1 Reprogramming Dictates Retinoid X Receptor Response in <i>ESR1</i>-Mutant Breast Cancer

S1. FOXA1 redistribution in ESR1 mutant cells causes distinct ER-FOXA1 interaction.S2. FOXA1 gained peaks annotated genes are significantly associated with novel target genes.S3. FOXA1 redistribution in ESR1 mutant cells confers potential RXR binding sites.S4. RXR agonist LG100268 can promote colonization and growth of ESR1 mutant cells.S5. Clonogenic survival assay and 2D growth assay to test RXR response in Park and Gertz MCF7 cell models.S6. FOXA1 knockdown drastically attenuated the base line growth of both ESR1 WT and mutant cells.S7. RXR antagonist HX531 can inhibit the response of ESR1 mutant cells to RXR agonist.S8. RXR antagonist HX531 can inhibit the basal and agonist promoted growth of IPM-PDXO-073 organoid.</p

Supplementary Tables 1-5 from FOXA1 Reprogramming Dictates Retinoid X Receptor Response in <i>ESR1</i>-Mutant Breast Cancer

Table S1. Data Sets UsedTable S2. FOXA1 and ER Chip-seq peaksTable S3. DE genesTable S4. Enriched FOXA1 peak motifsTable S5. Enriched IPA pathways</p