Depletion of MCP-1 increases development of herpetic stromal keratitis by innate immune modulation

Chemokines are important chemoattractant inflammatory molecules, but their interdependent network in disease pathogenesis remains unclear. Studies in mouse models have shown that herpetic stromal keratitis (SK) is produced by the consequence of a tissue-destructive immunoinflammatory reaction involving herpes simplex virus type 1 (HSV) infection. Here we found that ocular HSV infection leads to increased expression of monocyte chemoattractant protein-1 (MCP-1), one of the major chemoattractants for immune cells that express CCR2, in the SK cornea. However, MCP-1 is unlikely to be a chemoattractant for infiltrating Gr-1(+), CD11b(+) cells in SK, as these cells are found to be CCR2 negative. Nevertheless, infection of MCP-1(-/-) mice resulted in more severe SK lesion severity compared with WT mice (P<0.01). We demonstrated that the loss of MCP-1 in the SK cornea caused a significant overexpression of macrophage inflammatory protein-2 (MIP-2) (P<0.01) on days 2 and 4 postinfection and increased infiltration of inflammatory cells (Gr-1-high and CD11b(+)) expressing CXCR2, a receptor for MIP-2, into the cornea. Subsequently, increased infiltration of inflammatory cells accelerated by MIP-2 overexpression might result in the high production of inflammatory molecules, including vascular endothelial growth factor (VEGF) and IL-1beta in SK, as well as CpG oligodeoxynucleotide (ODN)-implanted eyes of MCP-1(-/-) mice. These results indicate that MCP-1 in the SK cornea might regulate the expression of other chemokines, as well as the infiltration of inflammatory cells and control development of SK.     

Evolving Paradigms in Classification of Primary Angle Closure Glaucoma

Purpose: To review the old and existing classification systems for primary angle closure disease. Methods: Literature review and new proposed classification system. Results: Existing classification systems have several shortcomings which cannot be applied in a clinical setting. This can be addressed by a proposed scoring system. Conclusion: A scoring system would be most appropriate for any clinical setting as well as for prognosticating primary angle closure disease.     

Separation and partial characterization of smooth muscle contractile material in the venom of the scorpion Heterometrus bengalensis

P. K. Kar, B. Sarangi, A. Datta, A. Gomes and S. C. Lahiri. Separation and partial characterization of smooth muscle contractile material in the venom of the scorpion Heterometrus bengalensis. Toxicon21, 353 – 361, 1983. — A smooth muscle contractile material was separated from crude venom of the scorpion Heterometrus bengalensis (found in Eastern India) by solvent extraction, gel filtration and thin layer chromatography. Smooth muscle contractile material could be extracted, in descending order of efficiency, with methanol, butanol, ethanol and acetone. The contractile material separated by gel filtration (Sephadex G-25) when further extracted, using the Folch procedure, showed a single spot in thin layer chromatography with one solvent system. Rechromatography of an eluate from this spot with another solvent system resolved it into three spots (SL1, SL2 and SL3, the mixture being designated as Substance L) which could be visualized either with iodine vapour, ninhydrin or molybdenum reagent. Eluates from the three spots contracted guinea-pig ileum which had been pretreated with antagonists of ACh, histamine, 5-HT and prostaglandins. Substance L and its fractions (SL1, SL2 and SL3) contain inorganic phosphorus, amino nitrogen and amino sugar, which point to the likelihood of their being glycophosphatides.     

The micropolitics of responsibility vis-à-vis autonomy: parental accounts of childhood genetic testing and (non)disclosure

Genetic testing and (non)disclosure of genetic information present ethical and moral dilemmas for the management of parental responsibility vis-à-vis the child's autonomy. Ethical guidelines aimed at professionals currently seek to defer childhood testing where there is no clear medical or psychosocial benefit. This version of autonomy is derived from a bioethical paradigm which brackets the individual rights and capacities of the child. In this paper we focus on situated parental accounts of responsibility/autonomy to understand the complex forms of relational work -i.e. the micropolitics of balancing rights and responsibilities - involving a range of inherited genetic disorders. Interviews (n= 20) were conducted with parents whose genetic condition may have had consequences for their children. Using rhetorical discourse analysis, we show how parents draw upon a number of rhetorical/discoursal devices to produce accounts where genetic responsibility is actually or potentially transmitted to the child. We identify three kinds of accounting practice: (1) aligned responsibility; (2) deferred responsibility; and (3) misaligned responsibility. Each of these practices demonstrates how parents position themselves responsibly by foregrounding figures and events onto which the child's autonomy is selectively mapped. Rather than simple representations, we regard these accounts as complex moral performances that seek alignment with broader bioethical discourses.     

Smartphone Apps as a Source of Cancer Information: Changing Trends in Health Information-Seeking Behavior

There is an increased interest in smartphone applications as a tool for delivery of health-care information. There have been no studies which evaluated the availability and content of cancer-related smartphone applications. This study aims to identify and analyze cancer-related applications available on the Apple iTunes platform. The Apple iTunes store was searched for cancer-related smartphone applications on July 29, 2011. The content of the applications was analyzed for cost, type of information, validity, and involvement of health-care agencies. A total of 77 relevant applications were identified. There were 24.6 % apps uploaded by health-care agencies, and 36 % of the apps were aimed at health-care workers. Among the apps, 55.8 % provided scientifically validated data. The difference in scientific validity between the apps aimed at general population versus health-care professionals was statistically significant (P?<?0.01). Seventy-nine percent of the apps uploaded by health-care agencies were found to be backed by scientific data. There is lack of cancer-related applications with scientifically backed data. There is a need to improve the accountability and reliability of cancer-related smartphone applications and encourage participation by health-care agencies to ensure patient safety.     

Cementless acetabular replacement in patients with rheumatoid arthritis: a 6- to 14-year prospective study

Sixty-three consecutive patients who had 82 Harris-Galante porous acetabular cups (HGP1) (Zimmer Inc, Warsaw, IN) implanted for the treatment of rheumatoid arthritis were prospectively assessed since 1986. At last examination, 12 patients (16 hips) had died, and 1 patient (1 hip) was lost to follow-up. A total of 65 hips in 50 patients were available for the latest review. The follow-up period was 6.8 years to 14 years (mean, 9.1 years). There had been 6 revisions: 1 for deep infection and 5 for polyethylene cup wear. Survivorship analysis for all failures estimated that 75% of hips would still be revision-free after 4558 days (12.5 years). Polyethylene wear has been identified in a further 7 cases at last examination. The average linear cup wear per year was 0.05 mm(range, 0.00-0.66 mm). There were no cases of acetabular loosening or acetabular migration. These results demonstrate the excellent durability of fixation of the HGP1 cups in patients with rheumatoid arthritis. However, a 32-mm head should probably not be used with this cup given the high associated incidence of polyethylene wear.     

Linking healthcare associated norovirus outbreaks: a molecular epidemiologic method for investigating transmission

Background  

Noroviruses are highly infectious pathogens that cause gastroenteritis in the community and in semi-closed institutions such as hospitals. During outbreaks, multiple units within a hospital are often affected, and a major question for control programs is: are the affected units part of the same outbreak or are they unrelated transmission events? In practice, investigators often assume a transmission link based on epidemiological observations, rather than a systematic approach to tracing transmission.     

Beyond prophylaxis: Extended risk of venous thromboembolism following primary debulking surgery for ovarian cancer

Objective

To determine the incidence and risk factors for venous thromboembolism (VTE) within six months after primary debulking surgery (PDS) for epithelial ovarian cancer (EOC).

Activation of Host Cellular Signaling and Mechanism of Enterovirus 71 Viral Proteins Associated with Hand,Foot and Mouth Disease

Enteroviruses are members of the Picornaviridae family consisting of human enterovirus groups A, B, C, and D as well as nonhuman enteroviruses. Human enterovirus type 71 (EV71) has emerged as a major cause of viral encephalitis, known as hand, foot, and mouth disease (HFMD), in children worldwide, especially in the Asia-Pacific region. EV71 and coxsackievirus A16 are the two viruses responsible for HFMD which are members of group A enteroviruses. The identified EV71 receptors provide useful information for understanding viral replication and tissue tropism. Host factors interact with the internal ribosome entry site (IRES) of EV71 to regulate viral translation. However, the specific molecular features of the respective viral genome that determine virulence remain unclear. Although a vaccine is currently approved, there is no effective therapy for treating EV71-infected patients. Therefore, understanding the host-pathogen interaction could provide knowledge in viral pathogenesis and further benefits to anti-viral therapy development. The aim of this study was to investigate the latest findings about the interaction of viral ligands with the host receptors as well as the activation of immunerelated signaling pathways for innate immunity and the involvement of different cytokines and chemokines during host-pathogen interaction. The study also examined the roles of viral proteins, mainly 2A and 3C protease, interferons production and their inhibitory effects.