Effect of surface modification of siliconeon Staphylococcus epidermidis adhesion and colonization

Cerebrospinal fluid (CSF) shunts for the treatment of hydrocephalus are generally made of silicone rubber. The growth of bacterial colonies on the silicone surface leads to frequent CSF shunt complications. A systematic study of the effect of the surface modification of silicone on Staphylococcus epidermidis adhesion and colonization was performed for different incubation times by means of colony counting and scanning electron microscopy (SEM). Silicone was modified with different biopolymers and silanes, including heparin, hyaluronan, octadecyltrichlorosilane (OTS), and fluoroalkylsilane (FAS) to provide a stable and biocompatible surface with different surface functional groups and degrees of hydrophobicity. The modified silicone surfaces were studied by using contact angle measurements, X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). After 4 and 8 h of incubation, the FAS- and OTS-coated silicone and the hyaluronan coated OTS/silicone surfaces showed significantly reduced bacterial adhesion and colonization compared to blank silicone by both quantification methods. However, the heparin coated OTS/silicone showed significantly increased bacterial adhesion. These results indicate that the nature of the surface functional group and surface roughness determine the extent of bacterial adhesion and colonization. However, the degree of hydrophobicity of the surface did not appear to play a determining role in bacterial adhesion and colonization. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55980/1/30952_ftp.pd

Mean-Field Description of Phase String Effect in the t−Jt-J Model

A mean-field treatment of the phase string effect in the $t-J$ model is presented. Such a theory is able to unite the antiferromagnetic (AF) phase at half-filling and metallic phase at finite doping within a single theoretical framework. We find that the low-temperature occurrence of the AF long range ordering (AFLRO) at half-filling and superconducting condensation in metallic phase are all due to Bose condensations of spinons and holons, respectively, on the top of a spin background described by bosonic resonating-valence-bond (RVB) pairing. The fact that both spinon and holon here are bosonic objects, as the result of the phase string effect, represents a crucial difference from the conventional slave-boson and slave-fermion approaches. This theory also allows an underdoped metallic regime where the Bose condensation of spinons can still exist. Even though the AFLRO is gone here, such a regime corresponds to a microscopic charge inhomogeneity with short-ranged spin ordering. We discuss some characteristic experimental consequences for those different metallic regimes. A perspective on broader issues based on the phase string theory is also discussed.Comment: 18 pages, five figure

Magnetic Incommensurability in Doped Mott Insulator

In this paper we explore the incommensurate spatial modulation of spin-spin correlations as the intrinsic property of the doped Mott insulator, described by the $t-J$ model. We show that such an incommensurability is a direct manifestation of the phase string effect introduced by doped holes in both one- and two-dimensional cases. The magnetic incommensurate peaks of dynamic spin susceptibility in momentum space are in agreement with the neutron-scattering measurement of cuprate superconductors in both position and doping dependence. In particular, this incommensurate structure can naturally reconcile the neutron-scattering and NMR experiments of cuprates.Comment: 12 pages (RevTex), five postscript figure

Incidence and risk factors of anti-tuberculosis drug induced liver injury (DILI): Large cohort study involving 4652 Chinese adult tuberculosis patients

Background and Aims: Anti-tuberculosis drugs remain as an important cause of drug-induced liver injury (DILI) worldwide. Adverse drug reactions reduce the effectiveness of treatment. We aimed to determine the incidence and risk factors associated with anti-tuberculosis DILI (ATDILI). Methods: Using established criteria and causality assessment methods, risk factors for ATDILI were identified in a contemporary cohort and validated in another cohort prospectively. Independent determinants of ATDILI were identified using Cox regression analysis. Results: In the derivation cohort (n=3155), 170 (5.4%) developed ATDILI of which 27 (15.9%) developed jaundice; 9(5.3%) developed acute liver failure (ALF) and 3 died. Among HBsAg positive patients, 11/27 (40.7%) of ATDILI developed after 3months of starting treatment. In addition, of 218 (6.9%) who developed raised alanine transferase (ALT) levels ≥3 times upper limit normal, 193 (88.5%) resolved and 25 (11.4%) progressed to DILI. Age (HR=1.014, 95% CI: 1.005-1.023), baseline ALT (HR=1.014, 95% CI: 1.003-1.024), haemoglobin (HR=1.011, 95% CI: 1.002-1.020) and HBsAg positivity (HR=1.516, 95% CI: 1.004-2.290) were independent risk factors for DILI. In the second cohort (n=1497) of which 85 (5.7%) developed ATDILI. Age (HR=1.029, 95% CI: 1.003-1.056), baseline AST (HR=1.036, 95% CI: 1.010-1.062), previous TB treatment (HR=3.894, 95% CI: 1.304-11.625) and active drinking (HR=3.624, 95% CI: 1.147-11.454) were risk factors for developing jaundice. Conclusion: Elevation of ALT of ≥3×ULN during anti-TB treatment resolves in the vast majority without developing serious consequences. In two cohorts involving 4652 patients, incidence of ALF and death because of ATDILI are low. Age, baseline ALT, haemoglobin and HBsAg positivity are risk factors for the development of DILI and these inform monitoring and management of these patients

Pyk2 activates the NLRP3 inflammasome by directly phosphorylating ASC and contributes to inflammasome-dependent peritonitis

The inflammasome adaptor protein, ASC, contributes to both innate immune responses and inflammatory diseases via self-oligomerization, which leads to the activation of the protease, caspase-1. Here, we report that the cytosolic tyrosine kinases, FAK and Pyk2, are differentially involved in NLRP3 and AIM2 inflammasome activation. The inhibition of FAK and Pyk2 with RNA interference or chemical inhibitors dramatically abolished ASC oligomerization, caspase-1 activation, and IL-1β secretion in response to NLRP3 or AIM2 stimulation. Pyk2 is phosphorylated by the kinase Syk and relocalizes to the ASC specks upon NLRP3 inflammasome activation. Pyk2, but not FAK, could directly phosphorylate ASC at Tyr146, and only the phosphorylated ASC could participate in speck formation and trigger IL-1β secretion. Moreover, the clinical-trial-tested Pyk2/FAK dual inhibitor PF-562271 reduced monosodium urate-mediated peritonitis, a disease model used for studying the consequences of NLRP3 activation. Our results suggest that although Pyk2 and FAK are involved in inflammasome activation, only Pyk2 directly phosphorylates ASC and brings ASC into an oligomerization-competent state by allowing Tyr146 phosphorylation to participate ASC speck formation and subsequent NLRP3 inflammation