Comprehensive evaluation of the safety and immunogenicity of a gene-deleted variant pseudorabies virus attenuated vaccine.

Pseudorabies virus (PRV) variant infections have caused a substantial economic impact on swine production in the absence of new powerful candidate vaccines. In this study, we developed and evaluated a gene-deleted variant pseudorabies virus (PRV)-attenuated vaccine, PRV GX-ΔTK/IES, in which the genes TK, gI, gE, US9 and US2 were deleted. During a study of innocuousness, all mice inoculated with PRV GX-ΔTK/IES survived, neither clinical signs nor pathological changes were observed, and viral genomes could not be detected in the blood and tissues. All piglets inoculated with high titres of PRV GX-ΔTK/IES remained clinically healthy, and neither fever nor clinical signs were observed. Viral detection results were negative in nasal swab samples, blood and tissue samples. Moreover, none of the cohabitated piglets seroconverted during a trial on horizontal transmission. The immunogenicity was assessed through a vaccination and challenge experiment in piglets. Piglets vaccinated with PRV GX-ΔTK/IES and the commercial vaccine were completely protected from subsequent PRV infection, and the level of immunity and protection induced by PRV GX-ΔTK/IES was better than that provided by the live commercial vaccine. Thus, PRV GX-ΔTK/IES is completely safe for both nontarget and target animals and can be regarded as a novel live gene-deleted PRV vaccine candidate.

Serum glycated albumin as good biomarker for predicting type 2 diabetes: A retrospective cohort study of China National Diabetes and Metabolic Disorders Survey.

AIMS: Glycated albumin (GA) is a biomarker for short-term (2-3 weeks) glycaemic control. However, the predictive utility of GA for diabetes and prediabetes is largely uncharacterised. We aimed to investigate the relationships of baseline serum GA levels with incident diabetes and prediabetes. METHODS: This was a longitudinal cohort study involving 516 subjects without diabetes or prediabetes at baseline. Blood glucose levels were observed during follow-up. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using COX proportional hazard models. Receiver operating characteristic curves and areas under the curves (AUCs) were used to evaluate the discriminating abilities of glycaemic biomarkers and prediction models. RESULTS: During a 9-year follow-up, 51 individuals (9.88%) developed diabetes and 92 (17.83%) prediabetes. Unadjusted HRs (95% CI) for both diabetes and prediabetes increased proportionally with increasing GA levels in a dose-response manner. Multivariable-adjusted HRs (95% CI) for diabetes were significantly elevated from 1.0 (reference) to 5.58 (1.86-16.74). However, the trend was no longer significant for prediabetes after multivariable adjustment. AUCs for GA, fasting blood glucose (FBG) and 2-h postprandial blood glucose (2h-PBG) for predicting diabetes were 0.698, 0.655 and 0.725, respectively. The AUCs for GA had no significant differences compared with those for FBG (p = 0.376) and 2h-PBG (p = 0.552). Replacing FBG or 2h-PBG or both with GA in diabetes prediction models made no significant changes to the AUCs of the models. CONCLUSIONS: GA is of good prognostic utility in predicting diabetes. However, GA may not be a useful biomarker for predicting prediabetes.

Targeted ultrasound contrast imaging of matrix metalloproteinase-2 in ischemia-reperfusion rat model: ex vivo and in vivo studies.

PURPOSE: We hypothesized that post-myocardial ischemia-reperfusion (I/R) remodeling associated matrix metalloproteinase-2 (MMP(2)) activation could be detected by using novel MMP(2) targeted ultrasound imaging. PROCEDURES: We study the combination of MMP(2)-targeted microbubbles (TMB(2)) and control microbubbles with myocardium in 1 week post-I/R rats. RESULTS: In in vitro studies, TMB(2) significantly bound within the risk area (RA) of 1-week post-I/R myocardial sections while rare binding was observed in the control area (CA). In in vivo studies, increased focal retention of TMB(2) was observed within the RA, with the higher myocardial video intensity (RA 42.85 ± 20.12 dB versus CA 25.85 ± 13.40 dB, p < 0.01). However, there was no difference of control microbubble retention in both CA and RA. CONCLUSIONS: A targeted ultrasound contrast imaging approach that employs novel TMB(2) has the potential to provide a less-invasive, higher-resolution technique for in vivo localization of MMP(2) activation and tracking of MMP-mediated post-I/R remodeling.