Background Presence of left atrial low voltage substrate in bipolar voltage mapping is associated with increased arrhythmia recurrences following pulmonary vein isolation for atrial fibrillation (AF). Besides local myocardial fibrosis, bipolar voltage amplitudes may be influenced by inter-electrode spacing and bipole-to-wavefront-angle. It is unclear to what extent these impact low voltage areas (LVA) in the clinical setting. Alternatively, unipolar electrogram voltage is not affected by these factors but requires advanced filtering. Objectives To assess the relationship between bipolar and unipolar voltage mapping in sinus rhythm (SR) and AF and identify if the electrogram recording mode affects the quantification and localization of LVA. Methods Patients (n = 28, 66±7 years, 46% male, 82% persistent AF, 32% redo-procedures) underwent high-density (>1,200 sites, 20 ± 10 sites/cm2, using a 20-pole 2-6-2 mm-spaced Lasso) voltage mapping in SR and AF. Bipolar LVA were defined using four different thresholds desSR and y = 1.22x + 0.12mV (r = 0.998) for AF. Conclusion Bipolar and unipolar voltage maps are highly correlated, in SR and AF. While bipole orientation and inter-electrode spacing are theoretical confounders, their impact is unlikely to be of clinical importance for localization of LVA, when mapping is performed at high density with a 20-polar Lasso catheter.Mathematical modeling in the field of glucose metabolism has a longstanding tradition. The use of models is motivated by several reasons. Models have been used for calculating parameters of physiological interest from experimental data indirectly, to provide an unambiguous quantitative representation of pathophysiological mechanisms, to determine indices of clinical usefulness from simple experimental tests. With the growing societal impact of type 2 diabetes, which involves the disturbance of the glucose homeostasis system, development and use of models in this area have increased. Following the approaches of physiological and clinical investigation, the focus of the models has spanned from representations of whole body processes to those of cells, i.e., from in vivo to in vitro research. Model-based approaches for linking in vivo to in vitro research have been proposed, as well as multiscale models merging the two areas. The success and impact of models has been variable. Two kinds of models have received rl models still need to develop their potential. This review illustrates the problems, approaches and contribution of mathematical modeling to the physiological and clinical investigation of glucose homeostasis and diabetes, focusing on the most relevant and stimulating models.The protein kinase enzyme family plays a pivotal role in almost every aspect of cellular function, including cellular metabolism, division, proliferation, transcription, movement, and survival. Protein kinase A (PKA), whose activation is triggered by cyclic adenosine monophosphate (cAMP), is widely distributed in various systems and tissues throughout the body and highly related to pathogenesis and progression of various kinds of diseases. The inhibition of PKA activation is essential for the study of PKA functions. Protein kinase inhibitor peptide (PKI) is a potent, heat-stable, and specific PKA inhibitor. It has been demonstrated that PKI can block PKA-mediated phosphorylase activation. Since then, researchers have a lot of knowledge about PKI. PKI is considered to be the most effective and specific method to inhibit PKA and is widely used in related research. In this review, we will first introduce the knowledge on the activation of PKA and mechanisms related on the inhibitory effects of PKI on PKA. Then, we will compare PKI-mediated PKA inhibition vs. several popular methods of PKA inhibition.Over the past 10 years, the crisis of sepsis has remained a great challenge. According to data from 2016, the sepsis-related mortality rate remains high. In addition, sepsis consumes extensive medical resources in intensive care units, and anti-inflammatory agents fail to improve sepsis-associated hyperinflammation and symptoms of immunosuppression. The specific immune mechanism of sepsis remains to be elucidated. Reactive oxygen species (ROS) are triggered by energy metabolism and respiratory dysfunction in sepsis, which not only cause oxidative damage to tissues and organelles, but also directly and indirectly promote NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation. NLRP3 inflammasomes enlarge the inflammatory response and trigger apoptosis of immune cells to exacerbate sepsis progression. Inhibiting the negative effects of ROS and NLRP3 inflammasomes therefore provides the possibility of reversing the excessive inflammation during sepsis.  https://www.selleckchem.com/products/CP-690550.html  In this review, we describe the interaction of ROS and NLRP3 inflammasomes during sepsis, provide prevention strategies, and identify fields that need further study.Repetitive complete or incomplete pharyngeal collapses are leading to chronic intermittent hypoxia (CIH), a hallmark feature of obstructive sleep apnea (OSA) syndrome responsible for many metabolic disorders. In humans, an association between OSA and insulin resistance has been found independently of the degree of obesity. Based on our previous work showing that hypoxia applied to adipocytes led to cellular insulin resistance associated with caveolae flattening, we have investigated the effects of CIH on caveolae structuration in adipose tissue. Original exploratory experiences demonstrate that 6 weeks-exposure of lean mice to CIH is characterized by systemic insulin resistance and translates into adipocyte insulin signaling alterations. Chronic intermittent hypoxia also induces caveolae disassembly in white adipose tissue (WAT) illustrated by reduced plasma membrane caveolae density and enlarged caveolae width, concomitantly to WAT insulin resistance state. We show that CIH downregulates caveolar gene and protein expressions, including cavin-1, cavin-2, and EHD2, underlying molecular mechanisms responsible for such caveolae flattening. Altogether, we provide evidences for adipose tissue caveolae disassembly following CIH exposure, likely linked to cavin protein downregulation. This event may constitute the molecular basis of insulin resistance development in OSA patients.