Serum NETosis expression and recurrence risk after regional or volatile anaesthesia during breast cancer surgery: A pilot, prospective, randomised single-blind clinical trial

Background: Some experimental and retrospective clinical studies signal an association between certain anaesthetic techniques and tumour metastasis following breast cancer surgery. Neutrophil Extracellular Trapping (NETosis) is an immunological process, whereby neutrophils engulf tumour antigen then degranulate, leaving a serologic marker. NETosis expression among breast cancer patients is associated with an increased risk of metastasis. We investigated the effect of two distinct anaesthetic techniques on the expression of NETosis in women who underwent potentially curative breast cancer surgery. Methods: In a parallel-group, randomised controlled trial, a subset of women (n = 40) undergoing breast cancer resection surgery, who were partaking in a larger trial (NCT00418457), were randomly assigned to receive volatile general anaesthesia (GA) or propofol GA combined with paravertebral regional anaesthesia (PPA) for their surgery. Serum was taken and stored before and 24 hours post-operatively. NETosis was measured by ELISA using Neutrophil Myeloperoxidase (MPO) and citrullinated histone H3 (H3Cit) biomarkers, which were the co-primary end points. Results: Patient and breast cancer characteristics did not differ significantly between groups. Recurrence occurred in 7.5% patients. GA patients received more opioids and reported higher post-operative pain than PPA. There was no difference in post-operative MPO in GA vs PPA (10.5 ± 6.6 vs 11.5 ± 4.7 ng mL−1, P =.60). Regarding CitH3, there was no difference post-operatively in GA vs PPA (3.6 ± 2.3 vs 4.0 ± 5.9, P =.80). NET expression did not differ before or after anaesthesia and surgery in either group, for either biomarker. Conclusion: Anaesthetic technique did not affect NETosis expression in breast cancer patients, indicating that it is not a viable marker of the effect of anaesthetic technique on breast cancer recurrence

The effects of sequential heat treatment on microbial reduction and spore inactivation during milk processing

peer-reviewedSequential heating processes are commonly applied to milk by the dairy industry as part of their microbiological control strategy. Often pasteurisation at 72 °C is followed by a sequential high heat treatment step of up to 125 °C; however, such severe heat treatment can lead to reduced protein quality. Nine temperature combinations (80–90 °C) were evaluated to assess microbial reduction and whey protein nitrogen index values during pilot scale milk processing. A total of 110 bacterial isolates were identified to species level by 16S rDNA sequencing, with Bacillus licheniformis identified as the dominant species. While the experimental treatments did not achieve microbial reductions comparable with the control heating process, the results of this study provide a benchmark for milk processors relative to the effects of sequential heat treatments on milk and their impact on the survival of both thermally resistant microbial populations and thermally labile milk components during processing.Department of Agriculture, Food and the Marine, Irelan

Dynamic Structure-Based Pharmacophore Model Development: A New and Effective Addition in the Histone Deacetylase 8 (HDAC8) Inhibitor Discovery

Histone deacetylase 8 (HDAC8) is an enzyme involved in deacetylating the amino groups of terminal lysine residues, thereby repressing the transcription of various genes including tumor suppressor gene. The over expression of HDAC8 was observed in many cancers and thus inhibition of this enzyme has emerged as an efficient cancer therapeutic strategy. In an effort to facilitate the future discovery of HDAC8 inhibitors, we developed two pharmacophore models containing six and five pharmacophoric features, respectively, using the representative structures from two molecular dynamic (MD) simulations performed in Gromacs 4.0.5 package. Various analyses of trajectories obtained from MD simulations have displayed the changes upon inhibitor binding. Thus utilization of the dynamically-responded protein structures in pharmacophore development has the added advantage of considering the conformational flexibility of protein. The MD trajectories were clustered based on single-linkage method and representative structures were taken to be used in the pharmacophore model development. Active site complimenting structure-based pharmacophore models were developed using Discovery Studio 2.5 program and validated using a dataset of known HDAC8 inhibitors. Virtual screening of chemical database coupled with drug-like filter has identified drug-like hit compounds that match the pharmacophore models. Molecular docking of these hits reduced the false positives and identified two potential compounds to be used in future HDAC8 inhibitor design

Multiresolution, perceptual and vector quantization based video codec

This paper presents a novel Multiresolution, Perceptual and Vector Quantization (MPVQ) based video coding scheme. In the intra-frame mode of operation, a wavelet transform is applied to the input frame and decorrelates it into its frequency subbands. The coefficients in each detail subband are pixel quantized using a uniform quantization factor divided by the perceptual weighting factor of that subband. The quantized coefficients are finally coded using a quadtree-coding algorithm. Perceptual weights are specifically calculated for the centre of each detail subband. In the inter-frame mode of operation, a Displaced Frame Difference (DFD) is first generated using an overlapped block motion estimation/compensation technique. A wavelet transform is then applied on the DFD and converts it into its frequency subbands. The detail subbands are finally vector quantized using an Adaptive Vector Quantization (AVQ) scheme. To evaluate the performance of the proposed codec, the proposed codec and the adaptive subband vector quantization coding scheme (ASVQ), which has been shown to outperform H.263 at all bitrates, were applied to six test sequences. Experimental results indicate that the proposed codec outperforms the ASVQ subjectively and objectively at all bit rates