A potential risk of overestimating apparent diffusion coefficient in parotid glands

Objectives: To investigate transient signal loss on diffusion weighted images (DWI) and overestimation of apparent diffusion coefficient (ADC) in parotid glands using single shot echoplanar DWI (EPDWI). Materials and Methods: This study enrolled 6 healthy subjects and 7 patients receiving radiotherapy. All participants received dynamic EPDWI with a total of 8 repetitions. Imaging quality of DWI was evaluated. Probability of severe overestimation of ADC (soADC), defined by an ADC ratio more than 1.2, was calculated. Error on T2WI, DWI, and ADC was computed. Statistical analysis included paired Student t testing and Mann-Whitney U test. A P value less than 0.05 was considered statistically significant. Results: Transient signal loss was visually detected on some excitations of DWI but not on T2WI or mean DWI. soADC occurred randomly among 8 excitations and 3 directions of diffusion encoding gradients. Probability of soADC was significantly higher in radiotherapy group (42.86%) than in healthy group (24.39%). The mean error percentage decreased as the number of excitations increased on all images, and, it was smallest on T2WI, followed by DWI and ADC in an increasing order. Conclusions: Transient signal loss on DWI was successfully detected by dynamic EPDWI. The signal loss on DWI and overestimation of ADC could be partially remedied by increasing the number of excitations. © 2015 Liu et al.published_or_final_versio

A simple and rapid approach for screening of SARS-coronavirus genotypes: an evaluation study

BACKGROUND: The Severe Acute Respiratory Syndrome (SARS) was a newly emerged infectious disease which caused a global epidemic in 2002–2003. Sequence analysis of SARS-coronavirus isolates revealed that specific genotypes predominated at different periods of the epidemic. This information can be used as a footprint for tracing the epidemiology of infections and monitor viral evolution. However, direct sequencing analysis of a large number of clinical samples is cumbersome and time consuming. We present here a simple and rapid assay for the screening of SARS-coronavirus genotypes based on the use of fluorogenic oligonucleotide probes for allelic discrimination. METHODS: Thirty SARS patients were recruited. Allelic discrimination assays were developed based on the use of fluorogenic oligonucleotide probes (TaqMan). Genotyping of the SARS-coronavirus isolates obtained from these patients were carried out by the allelic discrimination assays and confirmed by direct sequencing. RESULTS: Genotyping based on the allelic discrimination assays were fully concordant with direct sequencing. All of the 30 SARS-coronavirus genotypes studied were characteristic of genotypes previously documented to be associated with the latter part of the epidemic. Seven of the isolates contained a previously reported major deletion but in patients not epidemiologically related to the previously studied cohort. CONCLUSION: We have developed a simple and accurate method for the characterization and screening of SARS-coronavirus genotypes. It is a promising tool for the study of epidemiological relationships between documented cases during an outbreak

Cavitation in high-capacity tensiometers:effect of water reservoir surface roughness

High-capacity tensiometers (HCTs) are sensors made to measure negative pore water pressure (suction) directly. In this paper, a new approach is proposed to expand the range and duration of suction measurements for a newly designed HCT. A new technique is employed to reduce significantly the roughness of the diaphragm’s surface on the water reservoir side in order to minimise the possibility of gas nuclei development and the subsequent early cavitation at the water–diaphragm interface. The procedures employed for the design, fabrication, saturation and calibration of the new tensiometers are explained in detail. Furthermore, the performance of the developed HCTs is examined based on a series of experiments carried out on a number of unsaturated clay specimens. An improvement in maximum sustainable suction in the range of 120–150% of their nominal capacity was obtained from different surface treatment methods. Moreover, the results show an improvement of up to 177% for the long-term stability of measurements, compared to the developed ordinary HCTs with untreated diaphragms

Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70

Various subsets of invariant natural killer T (iNKT) cells with different cytokine productions develop in the mouse thymus, but the factors driving their differentiation remain unclear. Here we show that hypomorphic alleles of Zap70 or chemical inhibition of Zap70 catalysis leads to an increase of IFN-gamma-producing iNKT cells (NKT1 cells), suggesting that NKT1 cells may require a lower TCR signal threshold. Zap70 mutant mice develop IL-17-dependent arthritis. In a mouse experimental arthritis model, NKT17 cells are increased as the disease progresses, while NKT1 numbers negatively correlates with disease severity, with this protective effect of NKT1 linked to their IFN-gamma expression. NKT1 cells are also present in the synovial fluid of arthritis patients. Our data therefore suggest that TCR signal strength during thymic differentiation may influence not only IFN-gamma production, but also the protective function of iNKT cells in arthritis

RNAseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation as a Major Abnormality in ALS Spinal Cord

ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina) to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned \u3e50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2, DEseq2, EdgeR) for identification of differentially expressed genes (DEG’s). Ingenuity Pathways Analysis (IPA) and Weighted Gene Co-expression Network Analysis (WGCNA) identified inflammatory processes as significantly elevated in our ALS samples, with tumor necrosis factor (TNF) found to be a major pathway regulator (IPA) and TNFα-induced protein 2 (TNFAIP2) as a major network “hub” gene (WGCNA). Using the oPOSSUM algorithm, we analyzed transcription factors (TF) controlling expression of the nine DEG/hub genes in the ALS samples and identified TF’s involved in inflammation (NFkB, REL, NFkB1) and macrophage function (NR1H2::RXRA heterodimer). Transient expression in human iPSC-derived motor neurons of TNFAIP2 (also a DEG identified by all three algorithms) reduced cell viability and induced caspase 3/7 activation. Using high-density RNAseq, multiple algorithms for DEG identification, and an unsupervised gene co-expression network approach, we identified significant elevation of inflammatory processes in ALS spinal cord with TNF as a major regulatory molecule. Overexpression of the DEG TNFAIP2 in human motor neurons, the population most vulnerable to die in ALS, increased cell death and caspase 3/7 activation. We propose that therapies targeted to reduce inflammatory TNFα signaling may be helpful in ALS patients

Arsenic Trioxide Enhances the Radiation Sensitivity of Androgen-Dependent and -Independent Human Prostate Cancer Cells

Prostate cancer is the most common malignancy in men. In the present study, LNCaP (androgen-sensitive human prostate cancer cells) and PC-3 cells (androgen-independent human prostate cancer cells) were used to investigate the anti-cancer effects of ionizing radiation (IR) combined with arsenic trioxide (ATO) and to determine the underlying mechanisms in vitro and in vivo. We found that IR combined with ATO increases the therapeutic efficacy compared to individual treatments in LNCaP and PC-3 human prostate cancer cells. In addition, combined treatment showed enhanced reactive oxygen species (ROS) generation compared to treatment with ATO or IR alone in PC-3 cells. Combined treatment induced autophagy and apoptosis in LNCaP cells, and mainly induced autophagy in PC-3 cells. The cell death that was induced by the combined treatment was primarily the result of inhibition of the Akt/mTOR signaling pathways. Furthermore, we found that the combined treatment of cells pre-treated with 3-MA resulted in a significant change in AO-positive cells and cytotoxicity. In an in vivo study, the combination treatment had anti-tumor growth effects. These novel findings suggest that combined treatment is a potential therapeutic strategy not only for androgen-dependent prostate cancer but also for androgen-independent prostate cancer

Innate Immune Sensing of DNA

Discusses efforts to understand how DNA triggers immune responses