Clinical, echocardiographic, and pacing parameters affecting atrial fibrillation burden in patients with tachycardia-bradycardia syndrome

Background: The influence of various factors on atrial fibrillation (AF) development in the population of tachycardia-bradycardia syndrome (TBS) patients remains unclear. There are no data on the impact of different right ventricular pacing percentage (RVp%) profiles. Aim: The purpose of the study was to evaluate the relationship between the AF burden (AFB) and various clinical, echocardiographic, and pacing parameters in TBS patients. Methods: We performed a prospective, one-year registry of TBS patients with documented AF referred for dual-chamber pacemaker (DDD) implantation. Results: The data of 65 patients were analysed. The median 12-month RVp% and AFB was 9.4% and 1.0%, respectively. During the follow-up 14% of patients had no AF (p = 0.003), and the withdrawal of AF symptoms was observed in 49% of patients (p < 0.0001). The AFB was related to the left atrium diameter (r = 0.31, p = 0.02), especially in the subjects with left ventricular ejection fraction < 60% (r = 0.44, p = 0.04). Based on the relative change of RVp%, three groups of various RVp% profile were established: stable, decreasing, and increasing RVp%. In the stable RVp% group (n = 21) there was a quadratic correlation between the 12-month RVp% and AFB (r = 0.71, p = 0.0003). In the stable RVp% > 20% subgroup there was a significant increase of AFB in comparison to the RVp% ≤ 20% subgroup (ΔAFB 1.8% vs. 0.0%, p = 0.03, respectively). In the increasing RVp% group (n = 28) the AFB increased whereas in the decreasing RVp% (n = 16) it remained stable (ΔAFB 0.67% vs. 0.0%, p = 0.034, respectively). Conclusions: DDD implantation in TBS patients is related to a significant reduction in AF symptoms, and left atrial diameter correlates with cumulative AFB in the mid-term observation. Stable RVp% > 20% is associated with AF progression whereas lower stable RVp% may stabilise AF development. Increasing RVp% may be associated with the AFB increase in comparison to the decreasing RVp% subgroup in which AFB remains stable.Background: The influence of various factors on atrial fibrillation (AF) development in the population of tachycardia-bradycardia syndrome (TBS) patients remains unclear. There are no data on the impact of different right ventricular pacing percentage (RVp%) profiles. Aim: The purpose of the study was to evaluate the relationship between the AF burden (AFB) and various clinical, echocardiographic, and pacing parameters in TBS patients. Methods: We performed a prospective, one-year registry of TBS patients with documented AF referred for dual-chamber pacemaker (DDD) implantation. Results: The data of 65 patients were analysed. The median 12-month RVp% and AFB was 9.4% and 1.0%, respectively. During the follow-up 14% of patients had no AF (p = 0.003), and the withdrawal of AF symptoms was observed in 49% of patients (p < 0.0001). The AFB was related to the left atrium diameter (r = 0.31, p = 0.02), especially in the subjects with left ventricular ejection fraction < 60% (r = 0.44, p = 0.04). Based on the relative change of RVp%, three groups of various RVp% profile were established: stable, decreasing, and increasing RVp%. In the stable RVp% group (n = 21) there was a quadratic correlation between the 12-month RVp% and AFB (r = 0.71, p = 0.0003). In the stable RVp% > 20% subgroup there was a significant increase of AFB in comparison to the RVp% ≤ 20% subgroup (ΔAFB 1.8% vs. 0.0%, p = 0.03, respectively). In the increasing RVp% group (n = 28) the AFB increased whereas in the decreasing RVp% (n = 16) it remained stable (ΔAFB 0.67% vs. 0.0%, p = 0.034, respectively). Conclusions: DDD implantation in TBS patients is related to a significant reduction in AF symptoms, and left atrial diameter correlates with cumulative AFB in the mid-term observation. Stable RVp% > 20% is associated with AF progression whereas lower stable RVp% may stabilise AF development. Increasing RVp% may be associated with the AFB increase in comparison to the decreasing RVp% subgroup in which AFB remains stable

Nonsteroidal Anti-Inflammatory Drugs Prevent Vincristine-Dependent Cancer-Associated Fibroblasts Formation

Vincristine is used in the clinical treatment of colon cancer, especially in patients diagnosed in the advanced phase of cancer development. Unfortunately, similar to other agents used during antitumor therapy, vincristine might induce chemoresistance. Studies of this process focus mainly on the analysis of the molecular mechanisms within cancer, usually ignoring the role of stromal cells. Our present findings confirm that vincristine stimulates the secretion of tumor growth factors class beta and interleukin-6 from cancer-associated fibroblasts as a result of paracrine stimulation by cancer cells. Based on alterations in morphology, modulation of capillary formation, and changes in endothelial and mesenchymal marker profile, our findings demonstrate that higher levels of tumor growth factor-βs and interleukin-6 enhance cancer-associated fibroblast-like cell formation through endothelial–mesenchymal transition and that nonsteroidal anti-inflammatory drug treatment (aspirin and ibuprofen) is able to inhibit this phenomenon. The process appears to be regulated by the rate of microtubule polymerization, depending on β-tubulin composition. While higher levels of tubulin-β2 and tubulin-β4 caused slowed polymerization and reduced the level of factors secreted to the extracellular matrix, tubulin-β3 induced the opposite effect. We conclude that nonsteroidal anti-inflammatory drugs should be considered for use during vincristine monotherapy in the treatment of patients diagnosed with colorectal cancer

Cytoskeleton Reorganization in EndMT—The Role in Cancer and Fibrotic Diseases

Chronic inflammation promotes endothelial plasticity, leading to the development of several diseases, including fibrosis and cancer in numerous organs. The basis of those processes is a phenomenon called the endothelial–mesenchymal transition (EndMT), which results in the delamination of tightly connected endothelial cells that acquire a mesenchymal phenotype. EndMT-derived cells, known as the myofibroblasts or cancer-associated fibroblasts (CAFs), are characterized by the loss of cell–cell junctions, loss of endothelial markers, and gain in mesenchymal ones. As a result, the endothelium ceases its primary ability to maintain patent and functional capillaries and induce new blood vessels. At the same time, it acquires the migration and invasion potential typical of mesenchymal cells. The observed modulation of cell shape, increasedcell movement, and invasion abilities are connected with cytoskeleton reorganization. This paper focuses on the review of current knowledge about the molecular pathways involved in the modulation of each cytoskeleton element (microfilaments, microtubule, and intermediate filaments) during EndMT and their role as the potential targets for cancer and fibrosis treatment

Lactate Suppresses Retroviral Transduction in Cervical Epithelial Cells through DNA-PKcs Modulation

Recently, we have shown the molecular basis for lactate sensing by cervical epithelial cells resulting in enhanced DNA repair processes through DNA-PKcs regulation. Interestingly, DNA-PKcs is indispensable for proper retroviral DNA integration in the cell host genome. According to recent findings, the mucosal epithelium can be efficiently transduced by retroviruses and play a pivotal role in regulating viral release by cervical epithelial cells. This study examined the effects of lactate on lentiviral transduction in cervical cancer cells (HeLa, CaSki, and C33A) and model glioma cell lines (DNA-PKcs proficient and deficient). Our study showed that L- and D-lactate enhanced DNA-PKcs presence in nuclear compartments by between 38 and 63%, which corresponded with decreased lentiviral transduction rates by between 15 and 36%. Changes in DNA-PKcs expression or its inhibition with NU7441 also greatly affected lentiviral transduction efficacy. The stimulation of cells with either HCA1 agonist 3,5-DHBA or HDAC inhibitor sodium butyrate mimicked, in part, the effects of L-lactate. The inhibition of lactate flux by BAY-8002 enhanced DNA-PKcs nuclear localization which translated into diminished lentiviral transduction efficacy. Our study suggests that L- and D-lactate present in the uterine cervix may play a role in the mitigation of viral integration in cervical epithelium and, thus, restrict the viral oncogenic and/or cytopathic potential

Selected papers : law : language, norms, reasoning

Księga zawiera selekcję artykułów Profesora Tomasza Gizbert-Studnickiego, zawierającą 26 prac uporządkowanych w pięciu częściach tematycznych: (I) Prawo i język; (II) Teoria norm; (III) Metodologia prawoznawstwa i filozofia prawa; (IV) Wykładnia prawa, rozumowania i argumentacja prawnicza; oraz (V) W stronę dogmatyki prawa. Spośród tych 26 prac, pięć zostało po raz pierwszy opublikowanych w polskim tłumaczeniu: Ilu teorii prawdy potrzebuje prawoznawstwo? (org. How Many Theories of Truth Are Needed in Jurisprudence?, w przekładzie Wojciecha Ciszewskiego), Hermeneutyczna świadomość prawników (org. Das hermeneutische Bewusstsein der Juristen, w przekładzie Pawła Banasia), O ciężarze argumentacji w sporach prawnych (org. The Burden of Argumentation in Legal Disputes, w przekładzie Adama Dyrdy), Nielingwistyczne pojęcie normy i ontologia (org. The Non-Linguistic Concept of Norm and Ontology, w przekładzie Andrzeja Grabowskiego) oraz Typy nieostrości (org. Types of Vagueness, w przekładzie Michała Araszkiewicza