Crucial Involvement of IL-6 in Thrombus Resolution in Mice via Macrophage Recruitment and the Induction of Proteolytic Enzymes.

After the ligation of the inferior vena cava (IVC) of wild-type (WT) mice, venous thrombi formed and grew progressively until 5 days and resolved thereafter. Concomitantly, intrathrombotic gene expression of Il6 was enhanced later than 5 days after IVC ligation. IL-6 protein expression was detected mainly in F4/80-positive macrophages in thrombus. When Il6-deficient (Il6-/-) mice were treated in the same manner, thrombus mass was significantly larger than in WT mice. Moreover, the recovery of thrombosed IVC blood flow was markedly delayed in Il6-/- compared with WT mice. F4/80-positive macrophages in thrombus expressed proteolytic enzymes such as matrix metalloproteinase (Mmp) 2, Mmp9, and urokinase-type plasminogen activator (Plau); and their mRNA expression was significantly reduced in Il6-/- mice. Consistently, the administration of anti-IL-6 antibody delayed the thrombus resolution in WT mice, whereas IL-6 administration accelerated thrombus resolution in WT and Il6-/- mice. Moreover, IL-6 in vitro enhanced Mmp2, Mmp9, and Plau mRNA expression in WT-derived peritoneal macrophages in a dose-dependent manner; and the enhancement was abrogated by a specific Stat3 inhibitor, Stattic. Thus, IL-6/Stat3 signaling pathway can promote thrombus resolution by enhancing Mmp2, Mmp9, and Plau expression in macrophages.

The natural history of primary sclerosing cholangitis in 781 children: A multicenter, international collaboration.

There are limited data on the natural history of primary sclerosing cholangitis (PSC) in children. We aimed to describe the disease characteristics and long-term outcomes of pediatric PSC. We retrospectively collected all pediatric PSC cases from 36 participating institutions and conducted a survival analysis from the date of PSC diagnosis to dates of diagnosis of portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or death. We analyzed patients grouped by disease phenotype and laboratory studies at diagnosis to identify objective predictors of long-term outcome. We identified 781 patients, median age 12 years, with 4,277 person-years of follow-up; 33% with autoimmune hepatitis, 76% with inflammatory bowel disease, and 13% with small duct PSC. Portal hypertensive and biliary complications developed in 38% and 25%, respectively, after 10 years of disease. Once these complications developed, median survival with native liver was 2.8 and 3.5 years, respectively. Cholangiocarcinoma occurred in 1%. Overall event-free survival was 70% at 5 years and 53% at 10 years. Patient groups with the most elevated total bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis had the worst outcomes. In multivariate analysis PSC-inflammatory bowel disease and small duct phenotypes were associated with favorable prognosis (hazard ratios 0.6, 95% confidence interval 0.5-0.9, and 0.7, 95% confidence interval 0.5-0.96, respectively). Age, gender, and autoimmune hepatitis overlap did not impact long-term outcome. CONCLUSION: PSC has a chronic, progressive course in children, and nearly half of patients develop an adverse liver outcome after 10 years of disease; elevations in bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis can identify patients at highest risk; small duct PSC and PSC-inflammatory bowel disease are more favorable disease phenotypes. (Hepatology 2017;66:518-527).

Comparison between Outcomes of Vitrectomy in Granulomatous and Nongranulomatous Uveitis.

PURPOSE: The aim of this study was to compare the outcomes of vitrectomy in granulomatous uveitis and nongranulomatous uveitis insufficiently managed by immunosuppressive therapy. METHODS: Thirty-eight eyes with granulomatous uveitis and 17 eyes with nongranulomatous uveitis that underwent vitrectomy for ocular complications between July 2006 and August 2012 were reviewed retrospectively. Visual acuity and ocular inflammation scores before and 6 months after surgery were compared. Patients treated with vitrectomy alone and those in whom vitrectomy was combined with phacoemulsification were analyzed separately. RESULTS: The mean visual acuity improved significantly both in granulomatous and nongranulomatous uveitis. In granulomatous uveitis, the mean inflammation scores decreased significantly both in the anterior segment and in the posterior segment. In nongranulomatous uveitis, the mean inflammation score in the posterior segment decreased significantly, although it did not change in the anterior segment. CONCLUSION: Vitrectomy was effective for treating ocular complications both in granulomatous uveitis and nongranulomatous uveitis, with favorable outcomes of improved visual acuity and decreased uveitis activity.

Exotic quantum holonomy and higher-order exceptional points in quantum kicked tops.

The correspondence between exotic quantum holonomy, which occurs in families of Hermitian cycles, and exceptional points (EPs) for non-Hermitian quantum theory is examined in quantum kicked tops. Under a suitable condition, an explicit expression of the adiabatic parameter dependencies of quasienergies and stationary states, which exhibit anholonomies, is obtained. It is also shown that the quantum kicked tops with the complexified adiabatic parameter have a higher-order EP, which is broken into lower-order EPs with the application of small perturbations. The stability of exotic holonomy against such bifurcation is demonstrated.

Diffraction and tunneling in systems with mixed phase space.

The role of diffraction is investigated for two-dimensional area-preserving maps with sharply or almost sharply divided phase space, in relation to the issue of dynamical tunneling. The diffraction effect is known to appear in general when the system contains indifferentiable or discontinuous points. We find that it controls the quantum transition between regular and chaotic regions in mixed phase space in the case where the border between these regions is set to be sharp. However, its manifestation is rather subtle: it would be possible to identify the diffraction effect under suitable coordinates if the support of the wave function contains indifferentiable or discontinuous points, whereas it is mixed with the tunneling effect and the whole process becomes hybrid if the support does not contain the sources of diffraction. We make detailed analyses, including the semiclassical treatment of edge contributions of the one-step propagator, to clarify the nature of diffraction in mixed phase space. Our result implies that chaos does not play any roles in the regular-to-chaotic transition process when the phase space is sharply divided.

Dynamical tunneling in many-dimensional chaotic systems.

We investigate dynamical tunneling in many-dimensional systems using a quasiperiodically modulated kicked rotor, and find that the tunneling rate from the torus to the chaotic region is drastically enhanced when the chaotic states become delocalized as a result of the Anderson transition. This result strongly suggests that amphibious states, which were discovered for a one-dimensional kicked rotor with transporting islands [L. Hufnagel, Phys. Rev. Lett. 89, 154101 (2002)], quite commonly appear in many-dimensional systems.

Advantage of right ventricular outflow tract pacing on cardiac function and coronary circulation in comparison with right ventricular apex pacing.

BACKGROUND: The purpose of this study was to investigate the acute effect of right ventricular outflow tract (RVOT) pacing and right ventricular apex (RVA) pacing on synchronous ventricular activation and coronary flow dynamics. METHODS: We enrolled 20 consecutive patients who underwent electrophysiologic study. Echocardiographic study including two-dimensional tissue tracking imaging and Doppler guide wire examination was performed during RVOT pacing and RVA pacing. RESULTS: The improvement of left ventricular radial dyssynchrony (99 ± 12 ms vs. 142 ± 16 ms, P < .001), time-averaged peak velocities of coronary blood flow (54 ± 18 cm/s vs. 47 ± 17 cm/s, P = .007), and coronary microvascular resistance index (2.0 ± 0.8 vs. 2.4 ± 1.1, P = .028) was observed with RVOT pacing compared with RVA pacing. CONCLUSION: RVOT pacing might provide favorable effects on the left ventricular function and coronary flow dynamics over RVA pacing.

Recovery of chaotic tunneling due to destruction of dynamical localization by external noise.

Quantum tunneling in the presence of chaos is analyzed, focusing especially on the interplay between quantum tunneling and dynamical localization. We observed flooding of potentially existing tunneling amplitude by adding noise to the chaotic sea to attenuate the destructive interference generating dynamical localization. This phenomenon is related to the nature of complex orbits describing tunneling between torus and chaotic regions. The tunneling rate is found to obey a perturbative scaling with noise intensity when the noise intensity is sufficiently small and then saturate in a large noise intensity regime. A relation between the tunneling rate and the localization length of the chaotic states is also demonstrated. It is shown that due to the competition between dynamical tunneling and dynamical localization, the tunneling rate is not a monotonically increasing function of Planck's constant. The above results are obtained for a system with a sharp border between torus and chaotic regions. The validity of the results for a system with a smoothed border is also explained.

Quasienergy anholonomy and its application to adiabatic quantum state manipulation.

The parametric dependence of a quantum map under the influence of a rank-1 perturbation is investigated. While the Floquet operator of the map and its spectrum have a common period with respect to the perturbation strength lambda, we show an example in which none of the quasienergies nor the eigenvectors obey the same period: After a periodic increment of lambda, the quasienergy arrives at the nearest higher one, instead of the initial one, exhibiting an anholonomy, which governs another anholonomy of the eigenvectors. An application to quantum state manipulations is outlined.

Dynamical aspects of quantum entanglement for weakly coupled kicked tops.

We investigate how the dynamical production of quantum entanglement for weakly coupled, composite quantum systems is influenced by the chaotic dynamics of the corresponding classical system, using coupled kicked tops. The linear entropy for the subsystem (a kicked top) is employed as a measure of entanglement. A perturbative formula for the entanglement production rate is derived. The formula contains a correlation function that can be evaluated only from the information of uncoupled tops. Using this expression and the assumption that the correlation function decays exponentially which is plausible for chaotic tops, it is shown that the increment in the strength of chaos does not enhance the production rate of entanglement when the coupling is weak enough and the subsystems (kicked tops) are strongly chaotic. The result is confirmed by numerical experiments. The perturbative approach is also applied to a weakly chaotic region, where tori and chaotic sea coexist in the corresponding classical phase space, to reexamine a recent numerical study that suggests an intimate relationship between the linear stability of the corresponding classical trajectory and the entanglement production rate.

Saturation of the production of quantum entanglement between weakly coupled mapping systems in a strongly chaotic region.

The production of quantum entanglement between weakly coupled mapping systems, whose classical counterparts are both strongly chaotic, is investigated. In the weak-coupling regime, it is shown that time-correlation functions of the unperturbed systems determine the entanglement production. In particular, we elucidate that the increment of the nonlinear parameter of coupled kicked tops does not accelerate the entanglement production in the strongly chaotic region. An approach to the dynamical inhibition of entanglement is suggested.