Clinical Characteristics and Outcomes in 314 Japanese Patients with Bacterial Endophthalmitis : A Multicenter Cohort Study from J-CREST

Bacterial endophthalmitis is an intraocular infection that causes rapid vison loss. Pathogens can infect the intraocular space directly (exogenous endophthalmitis (ExE)) or indirectly (endogenous endophthalmitis (EnE)). To identify predictive factors for the visual prognosis of Japanese patients with bacterial endophthalmitis, we retrospectively examined the bacterial endophthalmitis characteristics of 314 Japanese patients and performed statistics using these clinical data. Older patients, with significantly more severe clinical symptoms, were prevalent in the ExE group compared with the EnE group. However, the final best-corrected visual acuity (BCVA) was not significantly different between the ExE and EnE groups. Bacteria isolated from patients were not associated with age, sex, or presence of eye symptoms. Genus Streptococcus, Streptococcus pneumoniae, and Enterococcus were more prevalent in ExE patients than EnE patients and contributed to poor final BCVA. The presence of eye pain, bacterial identification, and poor BCVA at baseline were risk factors for final visual impairment

Background Factors Affecting Visual Acuity at Initial Visit in Eyes with Central Retinal Vein Occlusion : Multicenter Study in Japan

Purpose: To determine the baseline characteristics of patients with central retinal vein occlusion (CRVO) that were significantly associated with the best-corrected visual acuity (BCVA) at the initial examination. Methods: This was a retrospective multicenter study using the medical records registered in 17 ophthalmological institutions in Japan. Patients with untreated CRVO (≥20-years-of-age) who were initially examined between January 2013 and December 2017 were studied. The patients’ baseline factors that were significantly associated with the BCVA at the initial examination were determined by univariate and multivariate linear regression analyses. Results: Data from 517 eyes of 517 patients were analyzed. Univariate analyses showed that an older age (r = 0.194, p < 0.001) and the right eye (r = −0.103, p < 0.019) were significantly associated with poorer BCVA at the initial visit. Multivariate analyses also showed that an older age (β = 0.191, p < 0.001) and the right eye (β = −0.089, p = 0.041) were significantly associated with poorer BCVA at the initial visit. Conclusions: The results indicate that an older age, a known strong factor, and the right eye were significantly associated with poorer BCVA at the initial visit to the hospital. These results suggest that functional and/or anatomical differences between the right and left eyes may be involved in these results

Bordetella evades the host immune system by inducing IL-10 through a type III effector, BopN

The inflammatory response is one of several host alert mechanisms that recruit neutrophils from the circulation to the area of infection. We demonstrate that Bordetella, a bacterial pathogen, exploits an antiinflammatory cytokine, interleukin-10 (IL-10), to evade the host immune system. We identified a Bordetella effector, BopN, that is translocated into the host cell via the type III secretion system, where it induces enhanced production of IL-10. Interestingly, the BopN effector translocates itself into the nucleus and is involved in the down-regulation of mitogen-activated protein kinases. Using pharmacological blockade, we demonstrated that BopN-induced IL-10 production is mediated, at least in part, by its ability to block the extracellular signal-regulated kinase pathway. We also showed that BopN blocks nuclear translocation of nuclear factor κB p65 (NF-κBp65) but, in contrast, promotes nuclear translocation of NF-κBp50. A BopN-deficient strain was unable to induce IL-10 production in mice, resulting in the elimination of bacteria via neutrophil infiltration into the pulmonary alveoli. Furthermore, IL-10–deficient mice effectively eliminated wild-type as well as BopN mutant bacteria. Thus, Bordetella exploits BopN as a stealth strategy to shut off the host inflammatory reaction. These results explain the ability of Bordetella species to avoid induction of the inflammatory response

Vascular Endothelial Growth Factor Induces Endothelial Fenestrations In Vitro

Abstract. Vascular endothelial growth factor (VEGF) is an important regulator of vasculogenesis, angiogenesis, and vascular permeability. In contrast to its transient expression during the formation of new blood vessels, VEGF and its receptors are continuously and highly expressed in some adult tissues, such as the kidney glomerulus and choroid plexus. This suggests that VEGF produced by the epithelial cells of these tissues might be involved in the induction or maintenance of fenestrations in adjacent endothelial cells expressing the VEGF receptors. Here we describe a defined in vitro culture system where fenestrae formation was induced in adrenal cortex capillary endothelial cells by VEGF, but not by fibroblast growth factor. A strong induction of endothelial fenestrations was observed in cocultures of endothelial cells with choroid plexus epithelial cells, or mammary epithelial cells stably transfected with cDNAs for VEGF 120 or 164, but not with untransfected cells. These results demonstrate that, in these cocultures, VEGF is sufficient to induce fenestrations in vitro. Identical results were achieved when the epithelial cells were replaced by an epithelial-derived basal lamina-type extracellular matrix, but not with collagen alone. In this defined system, VEGF-mediated induction of fenestrae was always accompanied by an increase in the number of fused diaphragmed caveolae-like vesicles. Caveolae, but not fenestrae, were labeled with a caveolin-1–specific antibody both in vivo and in vitro. VEGF stimulation led to VEGF receptor tyrosine phosphorylation, but no change in the distribution, phosphorylation, or protein level of caveolin-1 was observed. We conclude that VEGF in the presence of a basal lamina-type extracellular matrix specifically induces fenestrations in endothelial cells. This defined in vitro system will allow further study of the signaling mechanisms involved in fenestrae formation, modification of caveolae, and vascular permeability

Self-assisted Amoeboid Navigation in Complex Environments

Background: Living cells of many types need to move in response to external stimuli in order to accomplish their functional tasks; these tasks range from wound healing to immune response to fertilization. While the directional motion is typically dictated by an external signal, the actual motility is also restricted by physical constraints, such as the presence of other cells and the extracellular matrix. The ability to successfully navigate in the presence of obstacles is not only essential for organisms, but might prove relevant in the study of autonomous robotic motion. Methodology/principal findings: We study a computational model of amoeboid chemotactic navigation under differing conditions, from motion in an obstacle-free environment to navigation between obstacles and finally to moving in a maze. We use the maze as a simple stand-in for a motion task with severe constraints, as might be expected in dense extracellular matrix. Whereas agents using simple chemotaxis can successfully navigate around small obstacles, the presence of large barriers can often lead to agent trapping. We further show that employing a simple memory mechanism, namely secretion of a repulsive chemical by the agent, helps the agent escape from such trapping. Conclusions/significance: Our main conclusion is that cells employing simple chemotactic strategies will often be unable to navigate through maze-like geometries, but a simple chemical marker mechanism (which we refer to as "self-assistance") significantly improves success rates. This realization provides important insights into mechanisms that might be employed by real cells migrating in complex environments as well as clues for the design of robotic navigation strategies. The results can be extended to more complicated multi-cellular systems and can be used in the study of mammalian cell migration and cancer metastasis

Caveolin-1 overexpression is an early event in the progression of papillary carcinoma of the thyroid

Caveolin-1 is a major structural component of caveolae, which are plasma membrane microdomains implicated in the regulation of intracellular signalling pathways. Previous in vitro and in vivo studies on the function of caveolin-1 in carcinoma showed controversial results, indicating that the physiological role of caveolin-1 varies according to the origin of carcinoma. In this study, we investigated caveolin-1 expression in thyroid neoplasms by means of immunohistochemistry using a rabbit polyclonal antibody against caveolin-1. Normal follicular cells did not express caveolin-1. In papillary carcinoma, caveolin-1 expression was observed in high incidence, and especially in microcancer (less than 1.0 cm in diameter), caveolin-1 was positive in all cases except one. In undifferentiated (anaplastic) carcinoma, its incidence was significantly reduced. On the other hand, all cases of follicular carcinoma and adenoma were classified as negative for caveolin-1. These results suggest that caveolin-1 may play a role predominantly in the early phase of papillary carcinoma, whereas it has little influence on follicular tumours

Design concepts for the Cherenkov Telescope Array CTA: an advanced facility for ground-based high-energy gamma-ray astronomy

Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA