Assessment of Circulating MicroRNAs for the Diagnosis and Disease Activity Evaluation in Patients with Ulcerative Colitis by Using the Nanostring Technology

Background: Clinical decision and patient care management in inflammatory bowel diseases is largely based on the assessment of clinical symptoms, while the biomarkers currently in use poorly reflect the actual disease activity. Therefore, the identification of novel biomarkers will serve an unmet clinical need for IBD screening and patient management. We examined the utility of circulating microRNAs for diagnosis and disease activity monitoring in ulcerative colitis (UC) patients. Methods: Blood serum microRNAs were isolated from UC patients with active and inactive disease and healthy donors. High-throughput microRNA profiling was performed using the Nanostring technology platform. Clinical disease activity was captured by calculating the partial Mayo score. C-reactive protein (CRP) was measured in UC patients as part of their clinical monitoring. The profiles of circulating microRNAs and CRP were correlated with clinical disease indices. Results: We have identified a signature of 12 circulating microRNAs that differentiate UC patients from control subjects. Moreover, six of these microRNAs significantly correlated with UC disease activity. Importantly, a set of four microRNAs (hsa-miR-4454, hsa-miR-223-3p, hsa-miR-23a-3p, and hsa-miR-320e) which correlated with UC disease activity, were found to have higher sensitivity and specificity values than CRP. Conclusions: Circulating microRNAs provide a novel diagnostic and prognostic marker for UC patients. The use of an FDA approved platform could accelerate the application of microRNA screening in a GI clinical setting. When used in combination with current diagnostic and disease activity assessment modalities, microRNAs could improve both IBD screening and care management

Pan-European early switch/early discharge opportunities exist for hospitalised patients with methicillin-resistant <em>Staphylococcus</em> <em>aureus</em> complicated skin and soft-tissue infections

AbstractThe objective of this study was to document pan-European real-world treatment patterns and healthcare resource use and estimate opportunities for early switch (ES) from intravenous (IV) to oral antibiotics and early discharge (ED) in hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft tissue infections (cSSTIs). This retrospective observational medical chart review study enrolled 342 physicians across 12 European countries who collected data from 1542 patients with documented MRSA cSSTI who were hospitalized (July 2010 to June 2011) and discharged alive (by July 2011). Data included clinical characteristics and outcomes, hospital length of stay (LOS), MRSA-targeted IV and oral antibiotic use, and ES and ED eligibility according to literature-based and expert-validated criteria. The most frequent initial MRSA-active antibiotics were vancomycin (50.2%), linezolid (15.1%), clindamycin (10.8%), and teicoplanin (10.4%). Patients discharged with MRSA-active antibiotics (n = 480) were most frequently prescribed linezolid (42.1%) and clindamycin (19.8%). IV treatment duration (9.3 ± 6.5 vs. 14.6 ± 9.9 days; p <0.001) and hospital LOS (19.1 ± 12.9 vs. 21.0 ± 18.2 days; p 0.162) tended to be shorter for patients switched from IV to oral treatment than for patients who received IV treatment only. Of the patients, 33.6% met ES criteria and could have discontinued IV treatment 6.0 ± 5.5 days earlier, and 37.9% met ED criteria and could have been discharged 6.2 ± 8.2 days earlier. More than one-third of European patients hospitalized for MRSA cSSTI could be eligible for ES and ED, resulting in substantial reductions in IV days and bed-days, with potential savings of €2000 per ED-eligible patient

Professional development in teaching and learning for early career academic geographers: Contexts, practices and tensions

This is an Accepted Manuscript of an article published by Taylor & Francis in Journal of Geography in Higher Education on 16th May 2011, available online: doi: 10.1080/03098265.2011.563380This paper provides a review of the practices and tensions informing approaches to professional development for early career academic geographers who are teaching in higher education. We offer examples from Britain, Canada, Nigeria and the USA. The tensions include: institutional and departmental cultures; models that offer generic and discipline-specific approaches; the credibility of alternative settings for professional development in teaching and learning; the valuing of professional development and of teaching in academic systems of reward and recognition; and the challenges of balancing professional and personal life. We summarize concepts of good practice and suggest opportunities for future research

Identification of a Sex Pheromone Produced by Sternal Glands in Females of the Caddisfly Molanna angustata Curtis

In the caddisfly Molanna angustata, females produce a sex pheromone in glands with openings on the fifth sternite. Gas chromatographic analyses of pheromone gland extracts with electroantennographic detection revealed four major compounds that stimulated male antennae. These compounds were identified by means of gas chromatography–mass spectrometry and enantioselective gas chromatography as heptan-2-one, (S)-heptan-2-ol, nonan-2-one, and (S)-nonan-2-ol in the approximate ratio of 1:1:4:10, respectively. Field tests showed that the mixture of the two alcohols was attractive to males whereas addition of the corresponding ketones reduced trap catches. The sex pheromone of M. angustata, a species in the family Molannidae within the suborder Integripalpia, is similar to the pheromones or pheromone-like compounds previously reported from six other trichopteran families, including members of the basal suborder Annulipalpia. This suggests that minimal evolutionary change of the pheromone chemistry has taken place within the leptoceroid branch of integripalpian Trichoptera compared to the ancestral character state

Multi-megagauss field-generation using capacitor banks

Design of a high-field (6 MG) production experiment on the Pegasus capacitor bank is presented. One and two dimensions MHD simulations are benchmarked against Alikhanov`s previous experiments and used to support the design for the Pegasus experiment. Possible extensions to the Atlas facility, where production of 20 Mg fields may be possible, are also discussed

Weight-based antibiotic dosing in a real-world European study of complicated skin and soft-tissue infections due to methicillin-resistant <i>Staphylococcus aureus</i>

AbstractWe aimed to characterize real-world dosing of weight-based intravenous (IV) antibiotic therapy in patients hospitalized for methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft-tissue infections (cSSTIs). This was a subgroup analysis of a retrospective chart review that captured data from 12 European countries. The study included patients ≥18 years old, hospitalized with an MRSA cSSTI between 1 July 2010 and 30 June 2011 and discharged alive by 31 July 2011. Patients treated with IV vancomycin, teicoplanin or daptomycin at any stage during hospitalization were included in this analysis. Analyses were conducted at the regimen level (dosing in mg/kg or in mg, frequency, and total daily dose (TDD)), with potentially multiple regimens per patient, and the patient level, categorizing patients into low, standard (labelled) and high dosing groups according to their initial MRSA-targeted regimen. Among the 1502 patients in the parent study, 998 patients contributed a total of 1050 daptomycin, teicoplanin or vancomycin regimens. Across all regimens, the mean initial TDDs were 6.3 ± 1.9 mg/kg for daptomycin, 10.5 ± 4.9 mg/kg for teicoplanin and 28.5 ± 11.5 mg/kg for vancomycin. A total of 789 patients received first-line therapy with one of the above antibiotics. The majority of patients receiving first-line teicoplanin and daptomycin (96% and 80%, respectively) received higher than labelled cSSTI doses, whereas vancomycin doses were lower than labelled doses in >40% of patients. These real-world data reveal significant deviation from labelled antibiotic dosing in 12 European countries and the potential for suboptimal outcomes in patients with MRSA cSSTIs

Comparison of vancomycin and linezolid in patients with peripheral vascular disease and/or diabetes in an observational European study of complicated skin and soft-tissue infections due to methicillin-resistant <i>Staphylococcus aureus</i>

AbstractSuboptimal antibiotic penetration into soft tissues can occur in patients with poor circulation due to peripheral vascular disease (PVD) or diabetes. We conducted a real-world analysis of antibiotic treatment, hospital resource use and clinical outcomes in patients with PVD and/or diabetes receiving linezolid or vancomycin for the treatment of methicillin-resistant Staphylococcus aureus complicated skin and soft-tissue infections (MRSA cSSTIs) across Europe. This subgroup analysis evaluated data obtained from a retrospective, observational medical chart review study that captured patient data from 12 European countries. Data were obtained from the medical records of patients ≥ 18 years of age, hospitalized with an MRSA cSSTI between 1 July 2010 and 30 June 2011 and discharged alive by 31 July 2011. Hospital length of stay and length of treatment were compared between the treatment groups using inverse probability of treatment weights to adjust for clinical and demographic differences. A total of 485 patients had PVD or diabetes and received treatment with either vancomycin (n = 258) or linezolid (n = 227). After adjustment, patients treated with linezolid compared with vancomycin respectively had significantly shorter hospital stays (17.9 ± 13.6 vs. 22.6 ± 13.6 days; p < 0.001) and treatment durations (12.9 ± 7.9 vs. 16.4 ± 8.3 days; p < 0.001). The proportions of patients prescribed oral, MRSA-active antibiotics at discharge were 43.2% and 12.4% of patients in the linezolid and vancomycin groups, respectively (p < 0.001). The reduction in resource use may result in lower hospital costs for patients with PVD and/or diabetes and MRSA cSSTIs if treated with linezolid compared with vancomycin

Inflammatory bowel disease, such as Ulcerative colitis, is a risk factor for recurrent thromboembolic events: a case report

Ulcerative colitis (UC), a member of the family of inflammatory bowel disease (IBD), occurs worldwide. It has an incidence which in recent years has been rising in areas such as Southern Europe and Asia, while remaining relatively constant in Northern Europe and North America

Acetate Kinase Isozymes Confer Robustness in Acetate Metabolism

Acetate kinase (ACK) (EC no: 2.7.2.1) interconverts acetyl-phosphate and acetate to either catabolize or synthesize acetyl-CoA dependent on the metabolic requirement. Among all ACK entries available in UniProt, we found that around 45% are multiple ACKs in some organisms including more than 300 species but surprisingly, little work has been done to clarify whether this has any significance. In an attempt to gain further insight we have studied the two ACKs (AckA1, AckA2) encoded by two neighboring genes conserved in Lactococcus lactis (L. lactis) by analyzing protein sequences, characterizing transcription structure, determining enzyme characteristics and effect on growth physiology. The results show that the two ACKs are most likely individually transcribed. AckA1 has a much higher turnover number and AckA2 has a much higher affinity for acetate in vitro. Consistently, growth experiments of mutant strains reveal that AckA1 has a higher capacity for acetate production which allows faster growth in an environment with high acetate concentration. Meanwhile, AckA2 is important for fast acetate-dependent growth at low concentration of acetate. The results demonstrate that the two ACKs have complementary physiological roles in L. lactis to maintain a robust acetate metabolism for fast growth at different extracellular acetate concentrations. The existence of ACK isozymes may reflect a common evolutionary strategy in bacteria in an environment with varying concentrations of acetate