An Eye to a Kill: Using Predatory Bacteria to Control Gram-Negative Pathogens Associated with Ocular Infections

Ocular infections are a leading cause of vision loss. It has been previously suggested that predatory prokaryotes might be used as live antibiotics to control infections. In this study, Pseudomonas aeruginosa and Serratia marcescens ocular isolates were exposed to the predatory bacteria Micavibrio aeruginosavorus and Bdellovibrio bacteriovorus. All tested S. marcescens isolates were susceptible to predation by B. bacteriovorus strains 109J and HD100. Seven of the 10 P. aeruginosa isolates were susceptible to predation by B. bacteriovorus 109J with 80% being attacked by M. aeruginosavorus. All of the 19 tested isolates were found to be sensitive to at least one predator. To further investigate the effect of the predators on eukaryotic cells, human corneal-limbal epithelial (HCLE) cells were exposed to high concentrations of the predators. Cytotoxicity assays demonstrated that predatory bacteria do not damage ocular surface cells in vitro whereas the P. aeruginosa used as a positive control was highly toxic. Furthermore, no increase in the production of the proinflammatory cytokines IL-8 and TNF-alpha was measured in HCLE cells after exposure to the predators. Finally, injection of high concentration of predatory bacteria into the hemocoel of Galleria mellonella, an established model system used to study microbial pathogenesis, did not result in any measurable negative effect to the host. Our results suggest that predatory bacteria could be considered in the near future as a safe topical bio-control agent to treat ocular infections. © 2013 Shanks et al

Survey on Dynamic Query Forms for Database Queries

The databases used in today’s scientific research and web handle huge volumes of data. Such databases contain hundreds or even thousands of complex relations and attributes. The proposed system that implements dynamic query forms for non-relational data. The DQF captures a user’s preference and ranks query form components which assists the user in making decisions. Query form generation is an iterative process and initially requires user guidance in the form of feedback .The system automatically generates ranking list of form components, at each iteration and the desired form components are added by the user in Query forms. The ranking of form components depend on the captured user preference. The query results can be viewed at each iteration by the user after filling and submitting the query form. In order to measure the quality of the results generated by the Query form, a probabilistic model has been developed

National inter-rater agreement of standardised simulated-patient-based assessments.

PURPOSE: The forthcoming UK Medical Licensing Assessment will require all medical schools in the UK to ensure that their students pass an appropriately designed Clinical and Professional Skills Assessment (CPSA) prior to graduation and registration with a licence to practice medicine. The requirements for the CPSA will be set by the General Medical Council, but individual medical schools will be responsible for implementing their own assessments. It is therefore important that assessors from different medical schools across the UK agree on what standard of performance constitutes a fail, pass or good grade. METHODS: We used an experimental video-based, single-blinded, randomised, internet-based design. We created videos of simulated student performances of a clinical examination at four scripted standards: clear fail (CF), borderline (BD), clear pass (CPX) and good (GD). Assessors from ten regions across the UK were randomly assigned to watch five videos in 12 different combinations and asked to give competence domain scores and an overall global grade for each simulated candidate. The inter-rater agreement as measured by the intraclass correlation coefficient (ICC) based on a two-way random-effects model for absolute agreement was calculated for the total domain scores. RESULTS: 120 assessors enrolled in the study, with 98 eligible for analysis. The ICC was 0.93 (95% CI 0.81-0.99). The mean percentage agreement with the scripted global grade was 74.4% (range 40.8-96.9%). CONCLUSIONS: The inter-rater agreement amongst assessors across the UK when rating simulated candidates performing at scripted levels is excellent. The level of agreement for the overall global performance level for simulated candidates is also high. These findings suggest that assessors from across the UK viewing the same simulated performances show high levels of agreement of the standards expected of students at a 'clear fail,' 'borderline,' 'clear pass' and 'good' level.Cambridge NIHR Biomedical Research Centr

The antigenic determinant that defines thymic nurse cells is expressed by thymic epithelial progenitor cells

Stromal thymic epithelial cells with the multicellular structure unique to thymic nurse cells (TNCs) express the pH91 antigen on their cell surfaces. The multicellular TNC-complexes develop through an intimate association between αβTCR+CD4+CD8+ thymocytes and pH91-expressing cortical epithelial cells. TNCs participate in MHC-restriction and exhibit epithelial cell progenitor characteristics. In this report, we show that as early as E11.5 stage of thymus development, the pH91 antigen is expressed in association with K8, K5, Foxn1, and p63. The expression of these epithelial progenitor markers along with the pH91 antigen persists throughout thymic development in the murine thymus. At E13.5, pH91+ cells express relatively low levels of MHC class II. After E17.5, the first multicellular TNC complexes are recognizable along with increased cell surface expression of MHC class II. Our data suggest that epithelial cells bearing the “progenitor phenotype” develop into the multicellular TNCs

Kulturelna i metagenomska identifikacija mikrobioma kod supkliničkog mastitisa u krava.

Metagenomic and traditional microbial culture based analyses of milk samples from cows harbouring subclinical mastitis pathogens were carried out to identify the microbial community structure of milk. A total of 77 Triple cross (TP), Kankrej and Gir lactating cows and 301 quarters were screened for subclinical mastitis. A total of 106 isolates belonging to five different microbial genera were recovered from 91 quarters of 41 cows, including 15 quarters having mixed bacterial infections by cultural examination. Pyrosequencing readings obtained from the breed wise pooled DNA of subclinical mastitis milk samples were analyzed using the SEED subsystem database of Meta Genome Rapid Annotation with Subsystem Technology (MG-RAST). Among the five genera, Staphylococcus, Streptococcus, Micrococcus, Bacillus and Escherichia, detected in the subclinical mastitis milk samples by culture based methods, four genera, Staphylococcus, Streptococcus, Bacillus and Escherichia, were identified in the corresponding pyrosequencing data, while Micrococcus was not found. In contrast, the pyrosequencing yielded 28 bacterial species, of which only two species, S. aureus and E. coli, were identified by the cultural method. S. agalactiae, the third species identified by cultural method, was not found in the pyrosequencing data. Metagenomic analysis additionally identified 19 genera and 26 species in comparison with the routine cultural methods. Many of the fastidious / anaerobic bacterial organisms, which are difficult to cultivate by routine methods, were identified by metagenomic analyses.Radi identifikacije mikrobne zajednice u mlijeku provedena je metagenomska i uobičajena kulturelna pretraga uzoraka mlijeka krava sa supkliničkim mastitisom. Ukupno je 77 trostruko križanih Kankrej i Gir mliječnih krava i 301 četvrt vimena bilo pretraženo na supklinički mastitis. Izdvojeno je bilo 106 izolata svrstanih u pet različitih rodova iz 91 četvrti od 41 krave uključujući i 15 četvrti kod kojih je kulturelnom pretragom bila ustanovljena mješovita bakterijska infekcija. Sljedovi mješavine DNA izdvojeni iz uzoraka mlijeka kod supkliničkog mastitisa očitani pirosekvenciranjem bili su analizirani po podsustavu SEED baze podataka „Meta Genome Rapid Annotation with Subsystem Technology (MG-RAST)“. Iz pretraženih uzoraka mlijeka bilo je izdvojeno pet rodova: Staphylococcus, Streptococcus, Micrococcus, Bacillus i Escherichia. Četiri su bila dokazana postupkom pirosekvenciranja: Staphylococcus, Streptococcus, Bacillus i Escherichia, dok Micrococcus nije bio dokazan. S druge strane, pirosekvenciranjem je bilo dokazano 28 bakterijskih vrsta, od kojih su samo dvije, S. aureus i E. coli, bile dokazane klasičnom kulturelnom pretragom. S. agalactiae, treća vrsta identificirana kulturelnom pretragom nije bila dokazana postupkom pirosekvenciranja. Metagenomskom analizom dodatno je bilo dokazano 19 rodova i 26 vrsta u usporedbi s rutinskom kulturelnom pretragom. Mnoge anaerobne bakterije, koje je vrlo teško uzgojiti rutinskim metodama, bile su identificirane metagenomskom analizom

The fungal microbiota modulate neonatal oxygen-induced lung injury

Background: The immature lungs of very preterm infants are exposed to supraphysiologic oxygen, contributing to bronchopulmonary dysplasia (BPD), a chronic lung disease that is the most common morbidity of prematurity. While the microbiota significantly influences neonatal health, the relationship between the intestinal microbiome, particularly micro-eukaryotic members such as fungi and yeast, and lung injury severity in newborns remains unknown. Results: Here, we show that the fungal microbiota modulates hyperoxia-induced lung injury severity in very low birth weight premature infants and preclinical pseudohumanized and altered fungal colonization mouse models. Instead of fungal communities dominated by Candida and Saccharomyces, the first stool microbiomes of infants who developed BPD had less interconnected community architectures with a greater diversity of rarer fungi. After using a pseudohumanized model to show that transfer to the neonatal microbiome from infants with BPD increased the severity of lung injury, we used gain and loss of function approaches to demonstrate that modulating the extent of initial neonatal fungal colonization affected the extent of BPD-like lung injury in mice. We also identified alterations in the murine intestinal microbiome and transcriptome associated with augmented lung injury. Conclusions: These findings demonstrate that features of the initial intestinal fungal microbiome are associated with the later development of BPD in premature neonates and exert a microbiome-driven effect that is transferable and modifiable in murine models, which suggests both causality and a potential therapeutic strategy. 7tBaiGhHzrwGBbT1j3n_5hVideo Abstrac

Anticancer Evaluation of Adiantum venustum Don

Cancer is a malignant disease that is characterized by rapid and uncontrolled formation of abnormal cells which may mass together to form a growth or tumor, or proliferate throughout the body. Next to heart disease, cancer is a major killer of mankind. This study aims at a preliminary phytochemical screening and anticancer evaluation of Adiantum venustum Don against Ehrlich Ascites Carcinoma in animal model. The findings indicate that ethanolic extract of A. venustum Don possesses significant anticancer activity and also reduces elevated level of lipid peroxidation due to the presence of terpenoids and flavonoids. Thus, ethanolic extract of A. venustum Don could have vast therapeutic application against cancer