Animal Models of Diabetic Retinopathy (Part 2)

Diabetic retinopathy (DR) is one of the leading causes of preventable vision impairment and blindness in the working-age population worldwide. Numerous animal models have been developed for therapeutic drug screening and to further increase our understanding of the molecular and cellular pathological processes involved in DR. Following our discussion of mouse models in “Animal Models of Diabetic Retinopathy Part 1,” we describe the cellular, molecular, and morphological features of both rodent and nonrodent models of DR and their respective advantages and limitations in this chapter. To date, no animal model can holistically reproduce the pathological progression of human DR; most only display early or advanced lesions of DR. However, a thorough understanding of genotypic and phenotypic expressions of existing models will facilitate researchers’ selection of the appropriate model to simulate their desired clinical scenarios

3D visualization and 3D printing in abnormal gastrointestinal system manifestations of situs ambiguus

Situs ambiguus is a rare congenital condition whereby sufferers have abnormally positioned viscera (1,2). In such cases, it is dangerous to perform traditional diagnostic examinations, such as colonoscopy, thus anatomy is explored through invasive surgeries instead. By reconstructing a patient’s viscera three-dimensionally, it is possible to trace the physical origins of the patient’s symptoms, while eliminating the necessity for invasive surgery. We present a case of situs ambiguus with use of a combination of different approaches including 3D visualizations and patient-specific 3D printing technique to assist clinical diagnosis and patient management. This case highlights the potential value of utilising the latest visualization tools in the diagnostic assessment of complicated pathologies

Stemness and chemoresistance in epithelial ovarian carcinoma cells under shear stress

One of greatest challenges to the successful treatment of cancer is drug resistance. An exciting approach is the eradication of cancer stem cells (CSCs). However, little is known about key signals regulating the formation and expansion of CSCs. Moreover, lack of a reliable predictive preclinical model has been a major obstacle to discover new cancer drugs and predict their clinical activity. Here, in ovarian cancer, a highly chemoresistant tumor that is rapidly fatal, we provide the first evidence demonstrating the causal involvement of mechanical stimulus in the CSC phenotype using a customizable microfluidic platform and three-dimensional spheroids, which most closely mimic tumor behavior. We found that ovarian cancer cells significantly acquired the expression of epithelial-to-mesenchymal transition and CSC markers and a remarkable chemoresistance to clinically relevant doses of frontline chemotherapeutic drugs cisplatin and paclitaxel when grown under fluid shear stress, which corroborates with the physiological attainable levels in the malignant ascites, but not under static condition. Furthermore, we uncovered a new link of microRNA-199a-3p, phosphatidylinositol 3-kinase/Akt, and multidrug transporter activation in shear stress-induced CSC enrichment. Our findings shed new light on the significance of hydrodynamics in cancer progression, emphasizing the need of a flow-informed framework in the development of therapeutics

The association between distal findings and proximal colorectal neoplasia: a systematic review and meta-analysis

Objectives: Whether screening participants with distal hyperplastic polyps (HPs) detected by flexible sigmoidoscopy (FS) should be followed by subsequent colonoscopy is controversial. We evaluated the association between distal HPs and proximal neoplasia (PN)/advanced proximal neoplasia (APN) in asymptomatic, average-risk patients. Methods: We searched Ovid Medline, EMBASE, and the Cochrane Library from inception to 30 June 2016 and included all screening studies that examined the relationship between different distal findings and PN/APN. Data were independently extracted by two reviewers with disagreements resolved by a third reviewer. We pooled absolute risks and odds ratios (ORs) with a random effects meta-analysis. Seven subgroup analyses were performed according to study characteristics. Heterogeneity was characterized with theI2 statistics. Results: We analyzed 28 studies (104,961 subjects). When compared with normal distal findings, distal HP was not associated with PN (OR=1.16, 95% confidence interval (CI)=0.89–1.51,P=0.14,I2=40%) or APN (OR=1.09, 95% CI=0.87–1.36,P=0.39,I2=5%), while subjects with distal non-advanced or advanced adenoma had higher odds of PN/APN. Higher odds of PN/APN were observed for more severe distal lesions. Weaker association between distal and proximal findings was noticed in studies with higher quality, larger sample size, population-based design, and more stringent endoscopy quality-control measures. The Egger’s regression tests showed allP>0.05. Conclusions: Distal HP is not associated with PN/APN in asymptomatic screening population when compared with normal distal findings. Hence, the presence of distal HP alone detected by FS does not automatically indicate colonoscopy referral for all screening participants, as other risk factors of PN/APN should be considered

Text Line Segmentation of Historical Documents: a Survey

There is a huge amount of historical documents in libraries and in various National Archives that have not been exploited electronically. Although automatic reading of complete pages remains, in most cases, a long-term objective, tasks such as word spotting, text/image alignment, authentication and extraction of specific fields are in use today. For all these tasks, a major step is document segmentation into text lines. Because of the low quality and the complexity of these documents (background noise, artifacts due to aging, interfering lines),automatic text line segmentation remains an open research field. The objective of this paper is to present a survey of existing methods, developed during the last decade, and dedicated to documents of historical interest.Comment: 25 pages, submitted version, To appear in International Journal on Document Analysis and Recognition, On line version available at http://www.springerlink.com/content/k2813176280456k3

Baculovirus Transduction of Mesenchymal Stem Cells: In Vitro Responses and In Vivo Immune Responses After Cell Transplantation

Baculovirus holds great promise for the genetic modification of mesenchymal stem cells (MSCs). However, whether baculovirus transduction provokes undesired MSCs responses that might compromise their in vivo applications has yet to be examined. Hereby, we unraveled that baculovirus transduction of human MSCs upregulated the transcription of interleukin (IL)-1 beta, interferon (IFN)-alpha and IL-6, but not tumor necrosis factor (TNF)-alpha and IFN-gamma. However, only IL-6 secretion was detectable by enzyme-linked immunosorbent assay (ELISA). Baculovirus transduction also stimulated transient, low level upregulation of human leukocyte antigen I (HLA-I) on the human MSCs surface, yet it did not either altered the HLA-II expression or impaired the MSCs ability to inhibit lymphocyte proliferation. After transplantation into allogeneic rats, the transduced rat MSCs elicited transient, mild macrophage responses, but the cells remained tolerant as judged by the persistence of transplanted cells and absence of CD8(+) T cells infiltration. Besides, transplantation of the transduced MSCs did not provoke systemic induction of monocytes and CD8(+) T cells. This study, for the first time, explores the responses of MSCs to virus transduction and confirms the safety of transplanting baculovirus-engineered MSCs into immunocompetent animals for cell-based gene therapy

Measurement of Cosmic-ray Muon-induced Spallation Neutrons in the Aberdeen Tunnel Underground Laboratory

AbstractMuon-induced neutrons are one of the major backgrounds to various underground experiments, such as dark matter searches, low-energy neutrino oscillation experiments and neutrino-less double beta-decay experiments. Previous experiments on the underground production rate of muon-induced neutrons were mostly carried out either at shallow sites or at very deep sites. The Aberdeen Tunnel experiment aims to measure the neutron production rate at a moderate depth of 611 meters water equivalent. Our apparatus comprises of six layers of plastic-scintillator hodoscopes for tracking the incident cosmic-ray muons, and 760 L of gadolinium-doped liquid-scintillator for both neutron production and detection targets. In this paper, we describe the design and the performance of the apparatus. The preliminary result on the measurement of neutron production rate is also presented

Poultry Drinking Water Used for Avian Influenza Surveillance

Samples of drinking water from poultry cages, which can be collected conveniently and noninvasively, provide higher rates of influenza (H9N2) virus isolation than do samples of fecal droppings. Studies to confirm the usefulness of poultry drinking water for detecting influenza (H5N1) should be conducted in disease-endemic areas