Dynamic Regulation of Myosin Light Chain Phosphorylation by Rho-kinase

Myosin light chain (MLC) phosphorylation plays important roles in various cellular functions such as cellular morphogenesis, motility, and smooth muscle contraction. MLC phosphorylation is determined by the balance between activities of Rho-associated kinase (Rho-kinase) and myosin phosphatase. An impaired balance between Rho-kinase and myosin phosphatase activities induces the abnormal sustained phosphorylation of MLC, which contributes to the pathogenesis of certain vascular diseases, such as vasospasm and hypertension. However, the dynamic principle of the system underlying the regulation of MLC phosphorylation remains to be clarified. Here, to elucidate this dynamic principle whereby Rho-kinase regulates MLC phosphorylation, we developed a mathematical model based on the behavior of thrombin-dependent MLC phosphorylation, which is regulated by the Rho-kinase signaling network. Through analyzing our mathematical model, we predict that MLC phosphorylation and myosin phosphatase activity exhibit bistability, and that a novel signaling pathway leading to the auto-activation of myosin phosphatase is required for the regulatory system of MLC phosphorylation. In addition, on the basis of experimental data, we propose that the auto-activation pathway of myosin phosphatase occurs in vivo. These results indicate that bistability of myosin phosphatase activity is responsible for the bistability of MLC phosphorylation, and the sustained phosphorylation of MLC is attributed to this feature of bistability

Longitudinal strain of right ventricular free wall by 2-dimensional speckle-tracking echocardiography is useful for detecting pulmonary hypertension

Aims Echocardiography is widely used for screening pulmonary hypertension (PH). More recently developed two-dimensional speckle-tracking echocardiography (2D-STE) can assess regional deformation of the myocardium and is useful for detecting left ventricular dysfunction. However, its usefulness to assess right ventricular (RV) dysfunction is not clear. Therefore, the aim of this study was to investigate the ability of peak systolic strain (PSS) and post-systolic strain index (PSI) at the RV free wall determined by 2D-STE to detect PH. Main methods Thirty-six images (27 images from PH patients, nine from patients with connective tissue disease without PH) obtained by 2D-STE were analysed. We investigated the relationship between RV hemodynamics measured by right heart catheterization and PSS, PSI and other echocardiographic parameters reflecting RV overload including RV end-diastolic diameter (RVDd) and tricuspid valve regurgitant pressure gradient (TRPG). Key findings PSS, PSI, RVDd and TRPG were all correlated with mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR). Furthermore, when PSS and MPAP were measured twice, the change in PSS was correlated with the change in MPAP (r = 0.633, p = 0.037). Multivariate logistic regression analysis identified PSS as the only independent factor associated with MPAP ? 35 mm Hg [odds ratio (OR), 1.616; 95% confidence interval (CI) 1.017-2.567; p = 0.042] and PVR ? 400 dyn・s・cm- 5(OR, 1.804; 95% CI 1.131-2.877; p = 0.013). Furthermore, the optimal PSS cut-off value to detect an elevated MPAP and PVR was - 20.75%, based on receiver operating characteristic curve analysis. Significance PSS of the RV free wall might serve as a useful non-invasive indicator of PH

Survey of psychiatric symptoms among inpatients with COVID-19 using the Diagnosis Procedure Combination data and medical records in Japan

Physical symptoms such as fatigue and muscle weakness, and psychiatric symptoms like depression and anxiety are considered as complications and sequelae of COVID-19. This epidemiological study investigated the actual status of psychiatric symptoms and disorders caused by COVID-19, from four major university hospitals and five general hospitals in Fukuoka Prefecture, Japan, having a population of 5 million. We conducted a survey of psychiatric disorders associated with COVID-19 using Diagnosis Procedure Combination (DPC) data and the psychiatric records of the hospitals. In the study period from January 2019 to September 2021, 2743 COVID-19 admissions were determined from DPC data across the nine sites. These subjects had significantly more anxiety, depression, and insomnia, and were receiving higher rates of various psychotropic medications than controls influenza and respiratory infections. A review of psychiatric records revealed that the frequency of organic mental illness with insomnia and confusion was proportional to the severity of COVID-19 infection and that anxiety symptoms appeared independent of infection severity. These results indicate that COVID-19 is more likely to produce psychiatric symptoms such as anxiety and insomnia than conventional infections