The Role of Neutrophils in Corneal Wound Healing in HO-2 Null Mice

Our studies demonstrated that Heme oxygenase (HO), in particular, the constitutive HO-2, is critical for a self-resolving inflammatory and repair response in the cornea. Epithelial injury in HO-2 null mice leads to impaired wound closure and chronic inflammation in the cornea. This study was undertaken to examine the possible relationship between HO-2 and the recruitment of neutrophils following a corneal surface injury in wild type (WT) and HO-2 knockout (HO-2−/−) mice treated with Gr-1 monoclonal antibody to deplete peripheral neutrophils. Epithelial injury was performed by removing the entire corneal epithelium. Infiltration of inflammatory cell into the cornea in response to injury was higher in HO-2−/− than in WT. However, the rate of corneal wound closure following neutrophil depletion was markedly inhibited in both WT and HO-2−/− mice by 60% and 85%, respectively. Neutropenia induced HO-1 expression in WT but not in HO-2−/− mice. Moreover, endothelial cells lacking HO-2 expressed higher levels of the Midkine and VE-cadherin and displayed strong adhesion to neutrophils suggesting that perturbation in endothelial cell function caused by HO-2 depletion underlies the increased infiltration of neutrophils into the HO-2−/− cornea. Moreover, the fact that neutropenia worsened epithelial healing of the injured cornea in both WT and HO-2−/− mice suggest that cells other than neutrophils contribute to the exaggerated inflammation and impaired wound healing seen in the HO-2 null cornea

Evaluation of Transperineal Magnetic Resonance Imaging/Ultrasound-Fusion Biopsy Compared to Transrectal Systematic Biopsy in the Prediction of Tumour Aggressiveness in Patients with Previously Negative Biopsy

Objectives: We compared the transperineal MRI/ultrasoundfusion biopsy (fusPbx) to transrectal systematic biopsy (sys-Pbx) in patients with previously negative biopsy and investigated the prediction of tumour aggressiveness with regard to radical prostatectomy (RP) specimen. Material and Methods: A total of 710 patients underwent multiparametric magnetic resonance imaging (mpMRI), which was evaluated in accordance with Prostate Imaging Reporting and Data System (PI-RADS). The maximum PI-RADS (maxPI-RADS) was defined as the highest PI-RADS of all lesions detected in mpMRI. In case of proven prostate cancer (PCa) and performed RP, tumour grading of the biopsy specimen was compared to that of the RP. Significant PCa (csPCa) was defined according to Epstein criteria. Results: Overall, scPCa was detected in 40% of patients. The detection rate of scPCa was 33% for fusPbx and 25% for sysPbx alone (p < 0.005). Patients with a maxPI-RADS ≥3 and a prostate specific antigen (PSA)-density ≥0.2 ng/mL2 harboured more csPCa than those with a PSA-density < 0.2 ng/mL2 (41% [33/81] vs. 20% [48/248]; p < 0.001). Compared to the RP specimen (n = 140), the concordance of tumour grading was 48% (γ = 0.57), 36% (γ = 0.31) and 54% (γ = 0.6) in fusPbx, sysPbx and comPbx, respectively. Conclusions: The combination of fusPbx and sysPbx outperforms both biopsy modalities in patients with re-biopsy. Additionally, the PSA-density may represent a predictor for csPCa in patients with maxPI-RADS ≥3

An assessment of factors associated with quality of randomized controlled trials for smoking cessation

To reduce smoking-related diseases, a research priority is to develop effective interventions for smoking cessation, and evidence from randomized controlled trials (RCTs) is usually considered to be the most valid. However, findings from RCTs may still be misleading due to methodological flaws. This study aims to assess the quality of 1083 RCTs of smoking cessation interventions in 41 relevant Cochrane Systematic Reviews (CSRs). Logistic regression analysis was performed to identify significant variables associated with the quality of RCTs. It was found that evidence for smoking cessation from RCTs was predominantly from high income countries, and the overall quality was high in only 8.6% of the RCTs. High quality RCTs tended to have a larger sample size, to be more recently published, and conducted in multiple countries belonging to different income categories. In conclusion, the overall quality of RCTs of smoking cessation interventions is far from perfect, and more RCTs in less developed countries are required to generate high grade evidence for global tobacco control. Collaboration between researchers in developed and less developed countries should be encouraged

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Carotid Artery Stenosis: Comparison of 3D Time-of-Flight MR Angiography and Contrast-Enhanced MR Angiography at 3T

. Purpose. The aim of this study was to assess the correlation of 3D time-of-flight MR angiography (TOF MRA) and contrastenhanced MR angiography (CEMRA) for carotid artery stenosis evaluation at 3T. Material and Methods. Twenty-three patients (5 f, 18 m; mean age 61 y, age range 45-78 y) with internal carotid artery stenosis detected with ultrasonography were examined on a 3.0T MR system. The MR examination included both 3D TOF MRA and CEMRA of the carotid arteries. MR images were evaluated independently by two board-certified radiologists. Stenosis evaluation was based on a five-point scale. Stenosis grades determined by TOF and CEMRA were compared using Spearman&apos;s rank correlation coefficient and the Wilcoxon test. Cohen&apos;s Kappa was used to evaluate interrater reliability. Results. CEMRA detected stenosis in 24 (52%) of 46 carotids evaluated, while TOF detected stenosis in 27 (59%) of 46 carotids. TOF MRA yielded significantly higher results for stenosis grade in comparison to CEMRA ( = 0.014). Interrater agreement was very good for both TOF MRA ( = 0.93) and CEMRA ( = 0.93). Conclusion. At 3T, 3D TOF MRA should not be used as replacement for contrast-enhanced MRA of the carotid arteries, as it results in significantly higher stenosis grades

Intra-arterial and intravenous applications of Iosimenol 340 injection, a new non-ionic, dimeric, iso-osmolar radiographic contrast medium: phase 2 experience

Background: Iosimenol 340 injection is a new, dimeric, iso-osmolar, iodinated contrast medium for X-ray angiography. Purpose: To compare the safety and efficacy of iosimenol injection to iodixanol injection in two randomized, controlled phase 2 trials. Material and Methods: One hundred and forty-four adult patients were enrolled in the two trials, one for evaluation during arteriography and the other for evaluation during computed tomography. Safety was compared by assessing adverse events, vital signs, ECGs, and laboratory parameters. Efficacy was assessed as X-ray attenuation in the computed tomography (CT) trial and as the quality of contrast enhancement in the arteriography trial. Results: There were no statistically significant differences in terms of safety or efficacy between the two contrast media. Both were well tolerated upon intravenous as well as intra-arterial injection. The most common adverse event was a feeling of warmth (observed in 35.1% of the patients with Iosimenol injection and 44.3% with iodixanol injection). Conclusion: Iosimenol upon intravenous as well as upon intra-arterial injection exhibits a safety profile and shows an efficacy similar to that of iodixanol