Temporal expression and cellular origin of CC chemokine receptors CCR1, CCR2 and CCR5 in the central nervous system: insight into mechanisms of MOG-induced EAE

Background  

The CC chemokine receptors CCR1, CCR2 and CCR5 are critical for the recruitment of mononuclear phagocytes to the central nervous system (CNS) in multiple sclerosis (MS) and other neuroinflammatory diseases. Mononuclear phagocytes are effector cells capable of phagocytosing myelin and damaging axons. In this study, we characterize the regional, temporal and cellular expression of CCR1, CCR2 and CCR5 mRNA in the spinal cord of rats with myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-EAE). While resembling human MS, this animal model allows unique access to CNS-tissue from various time-points of relapsing neuroinflammation and from various lesional stages: early active, late active, and inactive completely demyelinated lesions.     

A novel,highly sensitive electrochemical 1,4-dioxane sensor based on reduced graphene oxide–curcumin nanocomposite

1,4-Dioxane is a carcinogenic, non-biodegradable, organic water pollutant which is used as a solvent in various industries. It is also formed as an undesired by-product in the cosmetic and pharmaceutical industry. Given its carcinogenicity and ability to pollute, it is desirable to develop a sensitive and selective sensor to detect it in drinking water and other water bodies. Current works on this sensor are very few and involve complex metal oxide composite systems. A sensitive electrochemical sensor for 1,4-dioxane was developed by modifying a glassy carbon electrode (GCE) with a reduced graphene oxide–curcumin (rGO–CM) nanocomposite synthesized by a simple solution approach. The prepared rGO–CM was characterized by X-ray Diffraction (XRD), Fourier Transform Infrared (FTIR) Spectroscopy, Raman spectroscopy, UV-Vis spectroscopy, and Scanning Electron Microscopy (SEM). The rGO–CM/GCE sensor was employed for the detection of 1,4-dioxane in the range of 0.1–100 μM. Although, the detection range is narrower compared to reported literature, the sensitivity obtained for the proposed sensor is far superior. Moreover, the limit of detection (0.13 μM) is lower than the dioxane detection target defined by the World Health Organization (0.56 μM). The proposed rGO–CM/GCE also showed excellent stability and good recovery values in real sample (tap water and drinking water) analysis.

Reduced graphene oxide–curcumin (rGO–CM) nanocomposite was prepared from graphite oxide using curcumin. The rGO–CM/GCE was used for highly sensitive 1,4-dioxane detection. The LOD obtained (0.13 μM) was lower than the WHO guideline value.     

An evaluation of stereoacuity (3D vision) in practising surgeons across a range of surgical specialities

BackgroundJudging depth is important in surgery. Although there are several cues that permit depth perception, stereoacuity has been singled out as a possible predictor of surgical ability. However, it is not clear whether high-grade stereoacuity is necessary for a career in surgery. To help answer this, we aimed to evaluate stereoacuities in practising surgeons across a range of surgical specialities.MethodsWe recorded stereoacuity values on 66 surgeons working at a London teaching hospital using three standard stereotests: Titmus, TNO and Frisby. There were 36 Trainees and 30 Consultants, covering 12 surgical specialities.ResultsMedian stereoacuities (with range) for the whole group were: 40 s arc on Titmus (40–800), 30 s arc on TNO (15–480) and 20 s arc on Frisby (20–600). Four surgeons had no recordable stereoacuity on TNO, and one was also unrecordable on Titmus. Three of these four were Consultants. Depending on the test used, high-grade stereopsis was found in 74%–83% of surgeons while reduced stereopsis was found in 2%–14% of surgeons.ConclusionWhile we found that most surgeons in current NHS practice have high-grade stereoacuity, there are also surgeons with reduced stereopsis and some with no stereopsis. The findings do not therefore support the assertion that high-grade stereopsis is a universal requirement for a career in surgery. It would be difficult to justify setting a stereoacuity criterion for entrance into a surgical training programme.     

Microvessel density and vascular endothelial growth factor expression in infiltrating lobular mammary carcinoma

Angiogenesis is an important prognostic factor in infiltrating ductal carcinoma (IDC). Vascular endothelial growth factor (VEGF) stimulates angiogenesis in vivo. VEGF expression has been correlated with high vascularity in IDC. However, little is known about the prognostic significance of microvessel density (MVD) and its correlation with the expression of VEGF in infiltrating lobular carcinoma (ILC). We analyzed tumor samples from 51 patients with primary classic ILC to determine the relationship between tumoral MVD and VEGF expression. Cases of pleomorphic lobular carcinoma and tubulolobular carcinoma were excluded. Five-micron thick sections obtained from formalin-fixed, paraffin-embedded tissue blocks were immunostained with antibodies to factor VIII-related antigen (Dako, Carpenteria, CA) and VEGF (Calbiochem, Boston, MA). The former was used for MVD analysis. The vessel counts from the three most vascular fields (x200 magnification) were recorded and the highest of the vessel counts of the three fields was designated as the MVD. The intensity of VEGF staining and the proportion of cells staining were scored. Both the vessel counts and the scoring of VEGF staining were evaluated by two independent pathologists. The Student's t-test and Wilcoxon rank sum test were used to compare mean MVD and VEGF scores according to various clinical and pathologic features. All significance tests were two-sided with an alpha-level of 0.05. There was good correlation between the MVD of each observer (correlation coefficient 0.775, p < 0.001). There was no correlation of MVD or VEGF score with the size or stage of the tumor. In addition, the MVD or VEGF score was not significantly different between axillary lymph node-positive cases and node-negative cases, between patients with recurrence and those without, and between patients who survived and those who died of disease. There was, however, a weak negative correlation between the MVD and VEGF expression (Spearman correlation coefficient -0.08). Neither MVD or VEGF immunoscore were associated with tumor recurrence or vital status in patients with ILC. The absence of a statistically significant positive correlation between MVD and VEGF expression suggests that other factors may play a more important role in the angiogenesis of ILC.     

HCV selection and HVR1 evolution in a chimpanzee chronically infected with HCV-1 over 12 years.

Aim: To study hepatitis C virus (HCV) selection and hypervariable region-1 (HVR1) evolution in a chimpanzee chronically infected with HCV-1 over 12 years after inoculation with a human factor VIII concentrate contaminated with HCV. Methods: From the inoculum, the earliest chimpanzee plasma and 12 annual plasma samples, HCV fragments including HVR1 were amplified followed by cloning and sequencing. Results: Five HCV subtypes - 1a, 1b, 2a, 2b, 3a - and multiple 1a strains were identified in the inoculum. Two 1a strains were found in the earliest chimpanzee sample, while a single HCV-1 strain was detected in the 12 annual samples. None of the chimpanzee sequences were identical to those found in the inoculum. Over 12 years, HVR1 patterns changed irregularly, but a few patterns showed identical nucleotide or amino acid sequences. In the last three years, the variety of HVR1 patterns decreased, while the proportion of major patterns increased. These corresponded to a higher virus load and a lower number of amino acid substitutions. Simultaneously, the HVR1 sequences became more similar to the consensus sequence of the 1a subtype. Conclusion: HCV selection was observed from the inoculum to the inoculated chimpanzee and from the early acute hepatitis to the persistent chronic infection. The selection occurred at three levels: among subtypes after transmission, among isolates during acute hepatitis and among quasispecies in chronic infection.