p21/Cyclin E pathway modulates anticlastogenic function of Bmi-1 in cancer cells.

Apart from regulating stem cell self-renewal, embryonic development and proliferation, Bmi-1 has been recently reported to be critical in the maintenance of genome integrity. In searching for novel mechanisms underlying the anticlastogenic function of Bmi-1, we observed, for the first time, that Bmi-1 positively regulates p21 expression. We extended the finding that Bmi-1 deficiency induced chromosome breaks in multiple cancer cell models. Interestingly, we further demonstrated that knockdown of cyclin E or ectopic overexpression of p21 rescued Bmi-1 deficiency-induced chromosome breaks. We therefore conclude that p21/cyclin E pathway is crucial in modulating the anticlastogenic function of Bmi-1. As it is well established that the overexpression of cyclin E potently induces genome instability and p21 suppresses the function of cyclin E, the novel and important implication from our findings is that Bmi-1 plays an important role in limiting genomic instability in cylin E-overexpressing cancer cells by positive regulation of p21.published_or_final_versio

Discordance between Liver Biopsy and FibroScan® in Assessing Liver Fibrosis in Chronic Hepatitis B: Risk Factors and Influence of Necroinflammation

BACKGROUND: Few studies have investigated predictors of discordance between liver biopsy (LB) and liver stiffness measurement (LSM) using FibroScan®. We assessed predictors of discordance between LB and LSM in chronic hepatitis B (CHB) and investigated the effects of necroinflammatory activity. METHODS: In total, 150 patients (107 men, 43 women) were prospectively enrolled. Only LSM with ≥ 10 valid measurements was considered reliable. Liver fibrosis was evaluated using the Laennec system. LB specimens <15 mm in length were considered ineligible. Reference cutoff LSM values to determine discordance were calculated from our cohort (6.0 kPa for ≥ F2, 7.5 kPa for ≥ F3, and 9.4 kPa for F4). RESULTS: A discordance, defined as a discordance of at least two stages between LB and LSM, was identified in 21 (14.0%) patients. In multivariate analyses, fibrosis stages F3-4 and F4 showed independent negative associations with discordance (P = 0.002; hazard ratio [HR], 0.073; 95% confidence interval [CI], 0.014-0.390 for F3-4 and P = 0.014; HR, 0.067; 95% CI, 0.008-0.574 for F4). LSM values were not significantly different between maximal activity grades 1-2 and 3-4 in F1 and F2 fibrosis stages, whereas LSM values were significantly higher in maximal activity grade 3-4 than 1-2 in F3 and F4 fibrosis stage (median 8.6 vs. 11.3 kPa in F3, P = 0.049; median 11.9 vs. 19.2 kPa in F4, P = 0.009). CONCLUSION: Advanced fibrosis stage (F3-4) or cirrhosis (F4) showed a negative correlation with discordance between LB and LSM in patients with CHB, and maximal activity grade 3-4 significantly influenced LSM values in F3 and F4

Automatic and fast segmentation of breast region-of-interest (ROI) and density in MRIs

Accurate segmentation of the breast region of interest (BROI) and breast density (BD) is a significant challenge during the analysis of breast MR images. Most of the existing methods for breast segmentation are semi-automatic and limited in their ability to achieve accurate results. This is because of difficulties in removing landmarks from noisy magnetic resonance images (MRI) due to similar intensity levels and the close connection to BROI. This study proposes an innovative, fully automatic and fast segmentation approach to identify and remove landmarks such as the heart and pectoral muscles. The BROI segmentation is carried out with a framework consisting of three major steps. Firstly, we use adaptive wiener filtering and k-means clustering to minimize the influence of noises, preserve edges and remove unwanted artefacts. The second step systematically excludes the heart area by utilizing active contour based level sets where initial contour points are determined by the maximum entropy thresholding and convolution method. Finally, a pectoral muscle is removed by using morphological operations and local adaptive thresholding on MR images. Prior to the elimination of the pectoral muscle, the MR image is sub divided into three sections: left, right, and central based on the geometrical information. Subsequently, a BD segmentation is achieved with 4 level fuzzy c-means (FCM) thresholding on the denoised BROI segmentation. The proposed method is validated using the 1350 breast images from 15 female subjects. The pixel-based quantitative analysis showed excellent segmentation results when compared with manually drawn BROI and BD. Furthermore, the presented results in terms of evaluation matrices: Acc, Sp, AUC, MR, P, Se and DSC demonstrate the high quality of segmentations using the proposed method. The average computational time for the segmentation of BROI and BD is 1 minute and 50 seconds

Transurethral resection of the prostate in Northern Nigeria, problems and prospects

<p>Abstract</p> <p>Background</p> <p>Benign prostatic hyperplasia (BPH) is the commonest disease of the urinary tract afflicting the ageing male and is the commonest neoplastic disease in men aged 50 years and above.</p> <p>Transurethral prostatectomy (TURP) is the ultimate treatment of choice for benign prostatic hyperplasia (BPH) due mainly to the preference of minimally invasive surgery, long term relief of symptoms and cost effectiveness. It is however not available to the majority of Nigerians in need of prostatic surgery in Public Health Institutions.</p> <p>Methods</p> <p>The records of patients who underwent prostatectomy in Aminu Kano Teaching Hospital, over the period June 2001 to July 2007 were examined. The bio data of patients and laboratory investigations performed were retrieved.</p> <p>Results</p> <p>Five Hundred and forty two patients were operated upon, out of which 40 were excluded due to open prostatectomy (22 patients), bladder neck stenosis (16 patients) or bladder tumour around the trigon (2 patients). The age range of the patients was 47–110 years with a mean of 67.2 years. 289 patients (80.1%) had urethral catheter in situ at presentation and 11 (3%) patients had suprapubic cystostomy of which only 3 (0.85%) had combined urethral stricture and BPH.</p> <p>Only 131 (26%) had their PSA measured which ranged from 2–100 ng/ml out of which 39(29.8% n = 131) patients had more than 4 ng/ml and cancer of the prostate and 1(0.8%, n = 131) patient had a PSA level of 4 ng/ml and malignant prostate.</p> <p>Hospital stay was 1–32 days (mean 7.9) and the mean follow up period was 5.6 months (range 0–60) and there were 17.5% complications comprising of urinary tract infection (UTI) 7.2%, Orchitis 2.2%, urinary incontinence 0.6%, atonic bladder 1%, erectile dysfunction 0.6%, cerebrovascular accident 0.4%, myocardial infarction 0.4%, deep vein thrombosis 0.4% and disseminated intravascular coagulopathy (DIC) 0.6% and 1.2% mortality. The cost of treatment inclusive of pre-admission investigations was US$615.00 (range US$ 300–1,300)</p> <p>Conclusion</p> <p>Despite advances in minimally invasive therapy for LUTH/BPH, TURP is the optimum treatment of choice for the ageing male of sub-Saharan Africa. It is however not available to the majority of patients in this region due to poor health allocation and inadequate facilities and training.</p

Control and Characterization of Individual Grains and Grain Boundaries in Graphene Grown by Chemical Vapor Deposition

The strong interest in graphene has motivated the scalable production of high quality graphene and graphene devices. Since large-scale graphene films synthesized to date are typically polycrystalline, it is important to characterize and control grain boundaries, generally believed to degrade graphene quality. Here we study single-crystal graphene grains synthesized by ambient CVD on polycrystalline Cu, and show how individual boundaries between coalescing grains affect graphene's electronic properties. The graphene grains show no definite epitaxial relationship with the Cu substrate, and can cross Cu grain boundaries. The edges of these grains are found to be predominantly parallel to zigzag directions. We show that grain boundaries give a significant Raman "D" peak, impede electrical transport, and induce prominent weak localization indicative of intervalley scattering in graphene. Finally, we demonstrate an approach using pre-patterned growth seeds to control graphene nucleation, opening a route towards scalable fabrication of single-crystal graphene devices without grain boundaries.Comment: New version with additional data. Accepted by Nature Material

Potentials of Mean Force for Protein Structure Prediction Vindicated, Formalized and Generalized

Understanding protein structure is of crucial importance in science, medicine and biotechnology. For about two decades, knowledge based potentials based on pairwise distances -- so-called "potentials of mean force" (PMFs) -- have been center stage in the prediction and design of protein structure and the simulation of protein folding. However, the validity, scope and limitations of these potentials are still vigorously debated and disputed, and the optimal choice of the reference state -- a necessary component of these potentials -- is an unsolved problem. PMFs are loosely justified by analogy to the reversible work theorem in statistical physics, or by a statistical argument based on a likelihood function. Both justifications are insightful but leave many questions unanswered. Here, we show for the first time that PMFs can be seen as approximations to quantities that do have a rigorous probabilistic justification: they naturally arise when probability distributions over different features of proteins need to be combined. We call these quantities reference ratio distributions deriving from the application of the reference ratio method. This new view is not only of theoretical relevance, but leads to many insights that are of direct practical use: the reference state is uniquely defined and does not require external physical insights; the approach can be generalized beyond pairwise distances to arbitrary features of protein structure; and it becomes clear for which purposes the use of these quantities is justified. We illustrate these insights with two applications, involving the radius of gyration and hydrogen bonding. In the latter case, we also show how the reference ratio method can be iteratively applied to sculpt an energy funnel. Our results considerably increase the understanding and scope of energy functions derived from known biomolecular structures

Advanced adenoma diagnosis with FDG PET in a visibly normal mucosa: a case report

<p>Abstract</p> <p>Background</p> <p>An accurate, early diagnosis and treatment of adenomatous polyp can curtail progression to colorectal cancer. F-18 fluorodeoxyglucose positron emission tomography (F-18 FDG PET) reveals the biochemical changes associated with the development of many cancers which precede the appearance of gross anatomical changes that may be visualized during surgical resection or via imaging with MR or CT.</p> <p>Intervention</p> <p>We detail the history of a 64 year old female who had a whole-body FDG PET scan as a part of an employee wellness program. A dose of 12.2 mCi of F-18 labeled FDG was administered.</p> <p>Results</p> <p>A focal cecal uptake with a standardized uptake value (SUV) of 8.9 was found on the PET scan. Conversely, only normal mucosa was observed during a colonoscopy done 2 months after the PET scan. Motivated by the PET scan finding, the colonoscopist performed a biopsy which revealed a villous adenoma without high grade dysplasia. Pathology from tissue extracted during an exploratory laparatomy completed one month later found the lesion to be a villous adenoma with high grade dysplasia.</p> <p>Conclusion</p> <p>Whole-body FDG PET scan revealed the biochemical metabolic changes in malignancy that preceded the appearance of any gross anatomical abnormality. A positive FDG PET scan indicative of colorectal cancer should be followed up with a colonoscopy and biopsy even in a visibly normal mucosa.</p