Bilirubin Present in Diverse Angiosperms

Background and aims: Bilirubin is an orange-yellow tetrapyrrole produced from the breakdown of heme by mammals and some other vertebrates. Plants, algae, and cyanobacteria synthesize molecules similar to bilirubin, including the protein-bound bilins and phytochromobilin which harvest or sense light. Recently, we discovered bilirubin in the arils of Strelitzia nicolai, the White Bird of Paradise Tree, which was the first example of this molecule in a higher plant. Subsequently, we identified bilirubin in both the arils and flowers of Strelitzia reginae, the Bird of Paradise Flower. In the arils of both species, bilirubin is present as the primary pigment, and thus functions to produce color. Previously, no tetrapyrroles were known to generate display color in plants. We were therefore interested in determining whether bilirubin is broadly distributed in the plant kingdom, and whether it contributes to color in other species

Equilibrium Simulation of the Slip Coefficient in Nanoscale Pores

Accurate prediction of interfacial slip in nanoscale channels is required by many microfluidic applications. Existing hydrodynamic solutions based on Maxwellian boundary conditions include an empirical parameter that depends on material properties and pore dimensions. This paper presents a derivation of a new expression for the slip coefficient that is not based on the assumptions concerning the details of solid-fluid collisions and whose parameters are obtainable from \textit{equilibrium} simulation. The results for the slip coefficient and flow rates are in good agreement with non-equilibrium molecular dynamics simulation.Comment: 11 pages, 4 figures, submitted to Phys Rev Let

IntAct:intra-operative fluorescence angiography to prevent anastomotic leak in rectal cancer surgery: a randomized controlled trial

Aim Anastomotic leak (AL) is a major complication of rectal cancer surgery. Despite advances in surgical practice, the rates of AL have remained static, at around 10–15%. The aetiology of AL is multifactorial, but one of the most crucial risk factors, which is mostly under the control of the surgeon, is blood supply to the anastomosis. The MRC/NIHR IntAct study will determine whether assessment of anastomotic perfusion using a fluorescent dye (indocyanine green) and near‐infrared laparoscopy can minimize the rate of AL leak compared with conventional white‐light laparoscopy. Two mechanistic sub‐studies will explore the role of the rectal microbiome in AL and the predictive value of CT angiography/perfusion studies. Method IntAct is a prospective, unblinded, parallel‐group, multicentre, European, randomized controlled trial comparing surgery with intra‐operative fluorescence angiography (IFA) against standard care (surgery with no IFA). The primary end‐point is rate of clinical AL at 90 days following surgery. Secondary end‐points include all AL (clinical and radiological), change in planned anastomosis, complications and re‐interventions, use of stoma, cost‐effectiveness of the intervention and quality of life. Patients should have a diagnosis of adenocarcinoma of the rectum suitable for potentially curative surgery by anterior resection. Over 3 years, 880 patients from 25 European centres will be recruited and followed up for 90 days. Discussion IntAct will rigorously evaluate the use of IFA in rectal cancer surgery and explore the role of the microbiome in AL and the predictive value of preoperative CT angiography/perfusion scanning

Expression and DNA methylation of TNF, IFNG and FOXP3 in colorectal cancer and their prognostic significance.

BACKGROUND: Colorectal cancer (CRC) progression is associated with suppression of host cell-mediated immunity and local immune escape mechanisms. Our aim was to assess the immune function in terms of expression of TNF, IFNG and FOXP3 in CRC. METHODS: Sixty patients with CRC and 15 matched controls were recruited. TaqMan quantitative PCR and methylation-specific PCR was performed for expression and DNA methylation analysis of TNF, IFNG and FOXP3. Survival analysis was performed over a median follow-up of 48 months. RESULTS: TNF was suppressed in tumour and IFNG was suppressed in peripheral blood mononuclear cells (PBMCs) of patients with CRC. Tumours showed enhanced expression of FOXP3 and was significantly higher when tumour size was >38 mm (median tumour size; P=0.006, Mann-Whitney U-test). Peripheral blood mononuclear cell IFNG was suppressed in recurrent CRC (P=0.01). Methylated TNFpromoter (P=0.003) and TNFexon1 (P=0.001) were associated with significant suppression of TNF in tumours. Methylated FOXP3cpg was associated with significant suppression of FOXP3 in both PBMC (P=0.018) and tumours (P=0.010). Reduced PBMC FOXP3 expression was associated with significantly worse overall survival (HR=8.319, P=0.019). CONCLUSIONS: We have detected changes in the expression of immunomodulatory genes that could act as biomarkers for prognosis and future immunotherapeutic strategies

Addressing the variation in adjuvant chemotherapy treatment for colorectal cancer: can a regional intervention promote national change?

Analysis of routine population‐based data has previously shown that patterns of surgical treatment for colorectal cancer can vary widely, but there is limited evidence available to determine if such variation is also seen in the use of chemotherapy. This study quantified variation in adjuvant chemotherapy across both England using cancer registry data and in more detail across the representative Yorkshire and Humber regions. Individuals with Stages II and III colorectal cancer who underwent major resection from 2014 to 2015 were identified. Rates of chemotherapy were calculated from the Systemic Anticancer Treatment database using multilevel logistic regression. Additionally, questionnaires addressing different clinical scenarios were sent to regional oncologists to investigate the treatment preferences of clinicians. The national adjusted chemotherapy treatment rate ranged from 2% to 46% (Stage II cancers), 19% to 81% (Stage III cancers), 24% to 75% (patients aged <70 years) and 5% to 46% (patients aged ≥70 years). Regionally, the rates of treatment and the proportions of treated patients receiving combination chemotherapy varied by stage (Stage II 4%‐26% and 0%‐55%, Stage III 48%‐71% and 40%‐84%) and by age (<70 years 35%‐68% and 49%‐91%; ≥70 years 15%‐39% and 6%‐75%). Questionnaire responses showed significant variations in opinions for high‐risk Stage II patients with both deficient and proficient mismatch repair tumours and Stage IIIB patients aged ≥70 years. Following a review of the evidence, open discussion in our region has enabled a consensus agreement on an algorithm for colorectal cancer that is intended to reduce variation in practice

Citrullination facilitates cross-reactivity of rheumatoid factor with non-IgG1 Fc epitopes in rheumatoid arthritis

Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs) are the two most prevalent autoantibodies in rheumatoid arthritis (RA), and are thought to have distinct autoantigen targets. Whilst RF targets the Fc region of antibodies, ACPAs target a far broader spectrum of citrullinated peptides. Here we demonstrate significant sequence and structural homology between proposed RF target epitopes in IgG1 Fc and the ACPA target fibrinogen. Two of the three homologous sequences were susceptible to citrullination, and this modification, which occurs extensively in RA, permitted significant cross-reactivity of RF+ patient sera with fibrinogen in both western blots and ELISAs. Crucially, this reactivity was specific to RF as it was absent in RF− patient and healthy control sera, and could be inhibited by pre-incubation with IgG1 Fc. These studies establish fibrinogen as a common target for both RF and ACPAs, and suggest a new mechanism in RF-mediated autoimmune diseases wherein RF may act as a precursor from which the ACPA response evolves

The accuracy of Multi-detector row CT for the assessment of tumor invasion of the mesorectal fascia in primary rectal cancer

PURPOSE: To evaluate the accuracy of Multi-detector row CT (MDCT) for the prediction of tumor invasion of the mesorectal fascia (MRF). MATERIALS AND METHODS: A total of 35 patients with primary rectal cancer underwent preoperative staging magnetic resonance imaging (MRI) and MDCT. The tumor relationship to the MRF, expressed in 3 categories (1--tumor free MRF = tumor distance > or = 1 mm; 2--threatened = distance < 1 mm; 3--invasion = distance 0 mm) was determined on CT by two observers at patient level and at different anatomical locations. A third expert reader evaluated the MRF tumor relationship on MRI, which served as reference standard. Receiver operating characteristic curves (ROC-curves) and areas under these curves (AUC) were calculated. The inter-observer agreement of CT was determined by using linear weighted kappa statistics. RESULTS: The AUC of CT for MRF invasion was 0.71 for observer 1 and 0.62 for observer 2. The inter-observer agreement was kappa = 0.34. The performance of CT at mid-high rectal levels was statistically significant better compared to low anterior (obs.1: AUC = 0.88 vs. 0.50; obs 2: AUC = 0.84 vs. 0.31; P < or = 0.040). CONCLUSION: Multi-detector row CT has a poor accuracy for predicting MRF invasion in low-anterior located tumors.The accuracy of CT significantly improves for tumors in the mid-high rectum. There is a high inconsistency among readers

T-staging of rectal cancer: accuracy of 3.0 Tesla MRI compared with 1.5 Tesla

OBJECTIVES: Magnetic resonance imaging (MRI) is not accurate in discriminating T1-2 from borderline T3 rectal tumors. Higher resolution on 3 Tesla-(3T)-MRI could improve diagnostic performance for T-staging. The aim of this study was to determine whether 3T-MRI compared with 1.5 Tesla-(1.5T)-MRI improves the accuracy for the discrimination between T1-2 and borderline T3 rectal tumors and to evaluate reproducibility. METHODS: 13 patients with non-locally advanced rectal cancer underwent imaging with both 1.5T and 3T-MRI. Three readers with different expertise evaluated the images and predicted T-stage with a confidence level score. Receiver operator characteristics curves with areas under the curve (AUC) and diagnostic parameters were calculated. Inter- and intra-observer agreements were calculated with quadratic kappa-weighting. Histology was the reference standard. RESULTS: Seven patients had pT1-2 tumors and six had pT3 tumors. AUCs ranged from 0.66 to 0.87 at 1.5T vs. 0.52-0.82 at 3T. Mean overstaging rate was 43% at 1.5T and 57% at 3T (P = 0.23). Inter-observer agreement was kappa 0.50-0.71 at 1.5T vs. 0.15-0.68 at 3T. Intra-observer agreement was kappa 0.71 at 1.5T and 0.76 at 3T. CONCLUSIONS: This is the first study to compare 3T with 1.5T MRI for T-staging of rectal cancer within the same patients. Our results showed no difference between 3T and 1.5T-MRI for the distinction between T1-2 and borderline T3 tumors, regardless of expertise. The higher resolution at 3T-MRI did not aid in the distinction between desmoplasia in T1-2-tumors and tumor stranding in T3-tumors. Larger studies are needed to acknowledge these findings