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871.
Purpose
To test the hypothesis that optic nerve head (ONH) deformation manifesting as changes in its mean surface height precedes thinning of the peripapillary retinal nerve fiber layer (RNFL) in experimental glaucoma (EG).Methods
68 rhesus macaque monkeys each had three or more baseline imaging sessions under manometric intraocular pressure (IOP) control to obtain average RNFL thickness (RNFLT) and the ONH surface topography parameter mean position of the disc (MPD). Laser photocoagulation was then applied to the trabecular meshwork of one eye to induce chronic, mild-to-moderate IOP elevation and bi-weekly imaging continued. Event analysis was applied to determine for each parameter when an ‘endpoint’ occurred (signficant change from baseline) for eight different endpoint criteria. Specificity was assessed in the group of 68 fellow control eyes. Classical signal detection theory and survival analysis were used to compare MPD with RNFLT.Results
Regardless of the endpoint criterion, endpoints were always more frequent for MPD than for RNFLT. The discriminability index (d’) was 2.7 ± 0.2 for MPD and 1.9 ± 0.2 for RNFLT (p<0.0001). Endpoints were reached by MPD an average of 1-2 months earlier than by RNFLT (p<0.01). At the onset of the first specific, detectable MPD change in EG eyes, there was still no significant change in RNFLT on average (p=0.29) and only 25% of individual eyes exhibited signficant reduction. In contrast, at onset of signficant RNFLT change, MPD had already changed an average of 101 µm from baseline (p<0.0001) and 71% of the individual eyes had exhibited significant change. The magnitude of MPD change was more than could be explained on the basis of axon loss alone.Conclusions
This study demonstrates that the average surface height of the ONH changes prior to any detectable loss of average peripapillary RNFL thickness in non-human primate eyes with experimental glaucoma. 相似文献872.
Ying Zhang Jing Hu Hong-Jun Lu Jian-Ping Li Ning Wang Wei-Wei Li Yong-Chun Zhou Jun-Yue Liu Sheng-Jun Wang Jing Wang Xia Li Wan-Ling Ma Li-Chun Wei Mei Shi 《PloS one》2013,8(11)
Purpose
To determine the optimal standardized uptake value (SUV) of 18F-fluorodeoxyglucose (18F-FDG) for positron emission tomography (PET) imaging, at which the PET-defined gross tumor volume (GTVPET) best matches with the pathological volume (GTVPATH) in the cervical cancer.Materials and Methods
Ten patients with the cervical cancer who underwent surgery were enrolled in this study. The excised specimens were processed for whole-mount serial sections and H-E staining. The tumor borders were outlined in sections under a microscope, histopathological images were scanned and the GTVPATH calculated. The GTVPET was delineated automatically by using various percentages relative to the maximal SUV and absolute SUV. The optimal threshold SUV was further obtained as the value at which the GTVPET best matched with the GTVPATH.Results
An average of 85±10% shrinkage of tissue was observed after the formalin fixation. The GTVPATH was 13.38±2.80 cm3 on average. The optimal threshold on percentile SUV and absolute SUV were 40.50%±3.16% and 7.45±1.10, respectively. The correlation analysis showed that the optimal percentile SUV threshold was inversely correlated with GTVPATH (p<0.05) and tumor diameter (p<0.05). The absolute SUV was also positively correlated with SUVmax (p<0.05).Conclusion
The pathological volume could provide the more accurate tumor volume. The optimal SUV of FDG for PET imaging by use of GTVPATH as standard for cervical cancer target volume delineation was thus determined in this study, and more cases are being evaluated to substantiate this conclusion. 相似文献873.
Guang-cong Liu Guo-yuan Sui Guang-ying Liu Yang Zheng Yan Deng Yan-yan Gao Lie Wang 《PloS one》2013,8(11)
Background
Although transfusion-transmitted infection of hepatitis B virus (HBV) threatens the blood safety of China, the nationwide circumstance of HBV infection among blood donors is still unclear.Objectives
To comprehensively estimate the prevalence of HBsAg positive and HBV occult infection (OBI) among Chinese volunteer blood donors through bayesian meta-analysis.Methods
We performed an electronic search in Pub-Med, Web of Knowledge, Medline, Wanfang Data and CNKI, complemented by a hand search of relevant reference lists. Two authors independently extracted data from the eligible studies. Then two bayesian random-effect meta-analyses were performed, followed by bayesian meta-regressions.Results
5957412 and 571227 donors were identified in HBsAg group and OBI group, respectively. The pooled prevalence of HBsAg group and OBI group among donors is 1.085% (95% credible interval [CI] 0.859%∼1.398%) and 0.094% (95% CI 0.0578%∼0.1655%). For HBsAg group, subgroup analysis shows the more developed area has a lower prevalence than the less developed area; meta-regression indicates there is a significant decreasing trend in HBsAg positive prevalence with sampling year (beta = −0.1202, 95% −0.2081∼−0.0312).Conclusion
Blood safety against HBV infection in China is suffering serious threats and the government should take effective measures to improve this situation. 相似文献874.
α-Hemolysin (α-HL) is a self-assembling, channel-forming toxin that is produced as a soluble monomer by Staphylococcus aureus strains. Until now, α-HL has been a significant virulence target for the treatment of S. aureus infection. In our previous report, we demonstrated that some natural compounds could bind to α-HL. Due to the binding of those compounds, the conformational transition of α-HL from the monomer to the oligomer was blocked, which resulted in inhibition of the hemolytic activity of α-HL. However, these results have not indicated how the binding of the α-HL inhibitors influence the conformational transition of the whole protein during the oligomerization process. In this study, we found that three natural compounds, Oroxylin A 7-O-glucuronide (OLG), Oroxin A (ORA), and Oroxin B (ORB), when inhibiting the hemolytic activity of α-HL, could bind to the “stem” region of α-HL. This was completed using conventional Molecular Dynamics (MD) simulations. By interacting with the novel binding sites of α-HL, the ligands could form strong interactions with both sides of the binding cavity. The results of the principal component analysis (PCA) indicated that because of the inhibitors that bind to the “stem” region of α-HL, the conformational transition of α-HL from the monomer to the oligomer was restricted. This caused the inhibition of the hemolytic activity of α-HL. This novel inhibition mechanism has been confirmed by both the steered MD simulations and the experimental data obtained from a deoxycholate-induced oligomerization assay. This study can facilitate the design of new antibacterial drugs against S. aureus. 相似文献
875.
Rong Xu QingFeng Han TongYing Zhu Yeping Ren JiangHua Chen HuiPing Zhao MengHua Chen Jie Dong Yue Wang ChuanMing Hao Rui Zhang Xiaohui Zhang Mei Wang Na Tian HaiYan Wang 《PloS one》2013,8(11)
Background
Diabetic patients on peritoneal dialysis (PD) have lower survival and are more likely complicated with inflammation than their non-diabetic counterparts. Here, we explored the interaction effects between diabetes and inflammation on the survival of PD patients.Methods
Overall, 2,264 incident patients were enrolled from a retrospective cohort study in China. Patients were grouped according to the baseline levels of high-sensitive C-reactive protein (hsCRP, ≤3 mg/L or >3 mg/L) or serum albumin (SA, ≥38 g/L or <38 g/L). Then, several multivariable adjusted stratified Cox regression models were constructed for these groups to explore the predicted role of diabetes on all-cause or cardiovascular death under inflammatory or non-inflammatory conditions.Results
Diabetics on PD were more likely to have inflammation than non-diabetics on PD, and they presented with elevated hsCRP (52.7% vs. 47.3%, P = 0.03) or decreased SA (77.9% vs. 62.7%, P < 0.001) levels. After stratification by size of center and controlling for confounding factors, diabetes was found to predict all-cause death in patients with hsCRP >3 mg/L or SA <38 g/L but not in patients with hsCRP ≤3 mg/L or SA ≥38 g/L. Similarly, the presence of diabetes was an indication of cardiovascular death in patients with hsCRP >3 mg/L or SA <38 g/L. However, if further adjusted by baseline cardiovascular disease, the predicted role of diabetes on death related to cardiovascular disease in patients with SA <38 g/L disappeared.Conclusion
Diabetic patients could do as well as non-diabetic patients without inflammation on peritoneal dialysis. Active strategies should be implemented to improve inflammation status in diabetic patients on PD. 相似文献876.
Both inflammatory processes associated with microglia activation and abnormal iron deposit in dopaminergic neurons are involved in the pathogenesis of Parkinson's disease (PD). However, the relationship between neuroinflammation and iron accumulation was not fully elucidated. In the present study, we aimed to investigate whether the pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) released by microglia, could affect cellular iron transportation in primary cultured ventral mesencephalic (VM) neurons. The results showed that IL-1β or TNF-α treatment led to increased ferrous iron influx and decreased iron efflux in these cells, due to the upregulation of divalent metal transporter 1 with the iron response element (DMT1 + IRE) and downregulation of ferroportin1 (FPN1). Increased levels of iron regulatory protein 1 (IRP1), transferrin receptor 1 (TfR1) and hepcidin were also observed in IL-1β or TNF-α treated VM neurons. IRP1 upregulation could be fully abolished by co-administration of radical scavenger N-acetyl-l-cysteine and inducible NO synthetase inhibitor Nω-nitro-l-arginine methyl ester hydrochloride. Further experiments demonstrated that IL-1β and TNF-α release was remarkably enhanced by iron load in activated microglia triggered by lipopolysaccharide or 1-methyl-4-phenylpyridinium (MPP+). In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mice, salicylate application could not block DMT1 + IRE upregulation in dopaminergic neurons of substantia nigra. These results suggested that IL-1β and TNF-α released by microglia, especially under the condition of iron load, might contribute to iron accumulation in VM neurons by upregulating IRP1 and hepcidin levels through reactive oxygen/nitrogen species production. This might provide a new insight into unraveling that microglia might aggravate this iron mediated neuropathologies in PD. 相似文献
877.
878.
Based on central composite rotatable experimental design and response surface method, the interacting effects of temperature (20 °C–34 °C) and dietary protein level (25%–50%) on hematological parameters including red blood cell (RBC), white blood cell (WBC) and hemoglobin (Hb) of juvenile Oreochromis niloticus were studied under laboratory conditions. The experiment lasted for 7 weeks. After the feeding trial, fish were challenged with Streptococcus iniae and mortality was recorded for within 8 days. Results showed that the linear and quadratic effects of temperature on RBC, WBC and Hb were highly significant (P < 0.01). When the dietary protein level was 25%–50%, the RBC, WBC and Hb were increased firstly and then decreased, but the linear and quadratic effects of protein level were insignificant (P > 0.05). The interacting effects of temperature and protein level on RBC and Hb were significant (P < 0.05). The regression equations of RBC, WBC and Hb toward the two factors of interest were established, with the coefficients of determination being 0.870, 0.836 and 0.881, respectively (P < 0.01). These equations could be used for prediction in practice. After the challenge, the mortalities for the combinations of 22.1 °C/28.7% and 20.0 °C/37.5% were significantly higher than 27.0 °C/37.5% (P < 0.05). The optimal temperature/dietary protein level combination was obtained at 27.9 °C/38.1% at which the lowest mortality (13.76%) was attained. This value was close to the optimal temperature/dietary protein level combination (29.4 °C/41.9%) for the greatest levels of RBC (2.560 × 106 μL?1), WBC (270.648 × 103 μL?1) and Hb (92.851 g L?1). The results of this study indicated that preferred temperature/dietary protein level combination might strengthen the non-specific immunity and reduce susceptibility to S. iniae. 相似文献
879.
Xing Wu Qunying Mao Xin Yao Pan Chen Xiangmei Chen Jie Shao Fan Gao Xiang Yu Fengcai Zhu Rongcheng Li Wenhui Li Zhenglun Liang Junzhi Wang Fengmin Lu 《PloS one》2013,8(6)
The level of neutralizing antibodies (NtAb) induced by vaccine inoculation is an important endpoint to evaluate the efficacy of EV71 vaccine. In order to evaluate the efficacy of EV71 vaccine, here, we reported the development of a novel pseudovirus system expression firefly luciferase (PVLA) for the quantitative measurement of NtAb. We first evaluated and validated the sensitivity and specificity of the PVLA method. A total of 326 serum samples from an epidemiological survey and 144 serum specimens from 3 clinical trials of EV71 vaccines were used, and the level of each specimen''s neutralizing antibodies (NtAb) was measured in parallel using both the conventional CPE-based and PVLA-based assay. Against the standard neutralization assay based on the inhibition of the cytopathic effect (CPE), the sensitivity and specificity of the PVLA method are 98% and 96%, respectively. Then, we tested the potential interference of NtAb against hepatitis A virus, Polio-I, Polio-II, and Polio-III standard antisera (WHO) and goat anti-G10/CA16 serum, the PVLA based assay showed no cross-reactivity with NtAb against other specific sera. Importantly, unlike CPE based method, no live replication-competent EV71 is used during the measurement. Taken together, PVLA is a rapid and specific assay with higher sensitivity and accuracy. It could serve as a valuable tool in assessing the efficacy of EV71 vaccines in clinical trials and disease surveillance in epidemiology studies. 相似文献
880.
A novel algebraic approach is proposed to study dynamics of asynchronous random Boolean networks where a random number of nodes can be updated at each time step (ARBNs). In this article, the logical equations of ARBNs are converted into the discrete-time linear representation and dynamical behaviors of systems are investigated. We provide a general formula of network transition matrices of ARBNs as well as a necessary and sufficient algebraic criterion to determine whether a group of given states compose an attractor of length in ARBNs. Consequently, algorithms are achieved to find all of the attractors and basins in ARBNs. Examples are showed to demonstrate the feasibility of the proposed scheme. 相似文献