EXPORTech (United States)

Background: Atrial fibrillation (AF) is a prevalent cardiovascular disease in the elderly population. Restoring sinus rhythm in AF often involves antiarrhythmic drugs, direct current (DC) cardioversion, and ablation. The predictive value of left atrial appendage (LAA) emptying velocity in determining the energy required for successful DC cardioversion remains uncertain. Aim: To study the association between LAA emptying velocity and the amount of energy required for cardioversion in patients with AF undergoing DC cardioversion. Methods: A total of 79 consecutive AF patients were enrolled in the study. Transesophageal echocardiography was performed to exclude the presence of clot formation, after which patients underwent DC cardioversion using escalating biphasic energy levels of 100 joules, 200 joules, and 360 joules to restore sinus rhythm. Patients were stratified into two groups based on LAA emptying velocity: the low-velocity group (≤30 cm/sec) and the high-velocity group (>30 cm/sec). Clinical characteristics were compared between the groups. Results: Of the 79 patients, 49 had a low LAA emptying velocity (LAAEV). The low-velocity group was older, with a mean age of 75 years compared to 70 years in the high-velocity group. The severity of mitral regurgitation was similar between the two groups. Patients with reduced LAA emptying velocity required significantly higher joules for successful cardioversion compared to the high-velocity group (192 joules vs. 155 joules, p-value = 0.02). Sleep apnea was more prevalent in the high-velocity group. The utilization of antiarrhythmic medications did not differ significantly between the groups (55% vs. 63%, p-value = 0.25). Conclusions: The study showed AF patients with low LAA emptying velocity require higher energy levels for successful cardioversion, suggesting that LAA emptying velocity may serve as a predictor of energy requirement in DC cardioversion for restoring sinus rhythm in AF patients.

Due to their immunoregulatory properties and capacity for multi-lineage differentiation, mesenchymal stem cells (MSCs) have been used as new therapeutic agents in regenerative medicine. Numerous lifestyle habits and behavioral risk factors may modulate metabolic and cell growth signaling pathways in MSCs, affecting their phenotype and function. Accordingly, identification of these factors and minimization of their influence on viability and function of transplanted MSCs may greatly contribute to their better therapeutic efficacy. A large number of experimental and clinical studies have demonstrated the detrimental effects of cigarette smoke and nicotine on proliferation, homing, chondrogenic and osteogenic differentiation of MSCs. Cigarette smoke down-regulates expression of chemokine receptors and modulates activity of anti-oxidative enzymes in MSCs, while nicotine impairs synthesis of transcriptional factors that regulate the cell cycle, metabolism, migration, chondrogenesis and osteogenesis. In this review article, we summarize current knowledge about molecular mechanisms that are responsible for cigarette smoke and nicotine-dependent modulation of MSCs' therapeutic potential.

BackgroundPericytes are multipotent cells present in every vascularized tissue in the body. Despite the fact that they are well-known for more than a century, pericytes are still representing cells with intriguing properties. This is mainly because of their heterogeneity in terms of definition, tissue distribution, origin, phenotype and multi-functional properties. The body of knowledge illustrates importance of pericytes in the regulation of homeostatic and healing processes in the body.Main bodyIn this review, we summarized current knowledge regarding identification, isolation, ontogeny and functional characteristics of pericytes and described molecular mechanisms involved in the crosstalk between pericytes and endothelial or immune cells. We highlighted the role of pericytes in the pathogenesis of fibrosis, diabetes-related complications (retinopathy, nephropathy, neuropathy and erectile dysfunction), ischemic organ failure, pulmonary hypertension, Alzheimer disease, tumor growth and metastasis with the focus on their therapeutic potential in the regenerative medicine. The functions and capabilities of pericytes are impressive and, as yet, incompletely understood. Molecular mechanisms responsible for pericyte-mediated regulation of vascular stability, angiogenesis and blood flow are well described while their regenerative and immunomodulatory characteristics are still not completely revealed. Strong evidence for pericytes’ participation in physiological, as well as in pathological conditions reveals a broad potential for their therapeutic use. Recently published results obtained in animal studies showed that transplantation of pericytes could positively influence the healing of bone, muscle and skin and could support revascularization. However, the differences in their phenotype and function as well as the lack of standardized procedure for their isolation and characterization limit their use in clinical trials.ConclusionCritical to further progress in clinical application of pericytes will be identification of tissue specific pericyte phenotype and function, validation and standardization of the procedure for their isolation that will enable establishment of precise clinical settings in which pericyte-based therapy will be efficiently applied.

As it is well known, 20th century applied mathematics with related physical and chemical theories, are solely applicable to point-like particles moving in vacuum under Hamiltonian interactions (exterior dynamical problems). In this note, we study the covering of 20th century mathematics discovered by R. M. Santilli, today known as Santilli isomathematics, representing particles as being extended, non-spherical and deformable while moving within a physical medium under Hamiltonian and non-Hamiltonian interactions (interior dynamical problems). In particular, we focus the attention on a central part of isomathematics given by the isorepresentations of the Lie-Santilli isoalgebras that have been classified into regular (irregular) isorepresentations depending on whether the structure quantities of the isocommutation rules are constants (functions of local variables). The importance of the study of the isorepresentation theory for a number of physical and chemical applications is pointed out

In this paper, we outline the various branches of hadronic mathematics and their applications to corresponding branches of hadronic mechanics and chemistry as conceived by the Italian-American scientist Ruggero Maria Santilli. According to said conception, hadronic mathematics comprises the following branches for the treatment of matter in conditions of increasing complexity: 1) 20th century mathematics based on Lie’s theory; 2) IsoMathematics based on Santilli’s isotopies of Lie’s theory; 3) GenoMathematics based on Santilli’s formulation of Albert’s Lie-admissibility; 4) HyperMathematics based on a multi-valued realization of genomathematics with classical operations; and 5) HyperMathematics based on Vougiouklis Hv hyperstructures expressed in terms of hyperoperations. Additionally, hadronic mathematics comprises the anti-Hermitean images (called isoduals) of the five preceding mathematics for the description of antimatter also in conditions of increasing complexity. The outline presented in this paper includes the identification of represented physical or chemical systems, the main mathematical structure, and the main dynamical equations per each branch. We also show the axiomatic consistency of various branches of hadronic mathematics as sequential coverings of 20th century mathematics; and indicate a number of open mathematical problems. Novel physical and chemical applications permitted by hadronic mathematics are presented in subsequent collections.

The safety and efficacy of the interferon-free combination of faldaprevir (NS3/A4 protease inhibitor), deleobuvir (BI 207127, non-nucleoside polymerase inhibitor), and ribavirin in treatment-naïve patients chronically infected with HCV genotype-1 was explored. SOUND-C3 was a multicenter, open-label Phase 2b study. Treatment-naïve patients chronically infected with HCV genotype-1a (IL28B CC genotype only; n = 12) and genotype-1b (n = 20) were assigned to 16 weeks of treatment with faldaprevir 120 mg once daily, deleobuvir 600 mg twice daily, and weight-based ribavirin. Patients with compensated liver disease, including cirrhosis, were eligible for inclusion in this study. The primary endpoint was sustained virological response 12 weeks after completion of therapy. Sustained virological response rates 12 weeks after completion of therapy were 17% and 95% in patients infected with HCV genotype-1a and genotype-1b respectively. All four patients with cirrhosis achieved sustained virological response 12 weeks after completion of therapy. The most frequently reported adverse events of at least moderate intensity were anaemia (16%), nausea, vomiting and fatigue (9% each). Three (9%) patients discontinued because of adverse events. The interferon-free regimen of faldaprevir, deleobuvir and ribavirin was efficacious in patients infected with genotype-1b and generally well tolerated.