Assessment of proliferating cell nuclear antigen and its relationship with proinflammatory cytokines and parameters of disease activity in multiple myeloma patients

Multiple myeloma (MM) is a malignant plasma cell disease. Several proinflammatory cytokines produced by malignant plasma cells and bone marrow (BM) stromal cells are involved in the pathogenesis of the disease. We evaluated serum levels of the proinflammatory cytokines Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Interleukin-8 (IL-8), macrophage inflammatory protein-1α (MIP-1α), in MM patients before treatment, and determined its significance in tumor progression. We also analyzed the correlation between measured parameters with proliferating cell nuclear antigen (PCNA). Forty-four MM patients and 20 healthy controls were studied. Serum levels of the proinflammatory cytokines were measured using enzyme-linked immunosorbent assay (ELISA), whereas PCNA value in the BM was determined by immunohistochemistry staining. The mean concentrations of the measured cytokines were significantly different among the three stages of disease, with higher values in advanced disease stage. Furthermore, patients with MM had significantly higher serum levels of the measured cytokines than in controls. A positive correlation was found between IL-6 with IL-1β, IL-8 and MIP-1α. Similarly, IL-8 and MIP-1α were positively correlated with markers of disease activity such as β2 microglobulin and LDH. The proliferation index, determined by PCNA immunostaining, was higher in advanced disease stage. Furthermore PCNA value correlated significantly with β2 microglobulin, LDH and the levels of the measured cytokines. Our results showed that the proliferative activity, as measured with PCNA, increases in parallel with disease stage. The positive correlation between PCNA and other measured mediators supports the involvement of these factors in the biology of myeloma cell growth and can be used as markers of disease activity and as possible therapeutic targets

MiMiR - an integrated platform for microarray data sharing, mining and analysis

Background: Despite considerable efforts within the microarray community for standardising data format, content and description, microarray technologies present major challenges in managing, sharing, analysing and re-using the large amount of data generated locally or internationally. Additionally, it is recognised that inconsistent and low quality experimental annotation in public data repositories significantly compromises the re-use of microarray data for meta-analysis. MiMiR, the Microarray data Mining Resource was designed to tackle some of these limitations and challenges. Here we present new software components and enhancements to the original infrastructure that increase accessibility, utility and opportunities for large scale mining of experimental and clinical data.Results: A user friendly Online Annotation Tool allows researchers to submit detailed experimental information via the web at the time of data generation rather than at the time of publication. This ensures the easy access and high accuracy of meta-data collected. Experiments are programmatically built in the MiMiR database from the submitted information and details are systematically curated and further annotated by a team of trained annotators using a new Curation and Annotation Tool. Clinical information can be annotated and coded with a clinical Data Mapping Tool within an appropriate ethical framework. Users can visualise experimental annotation, assess data quality, download and share data via a web-based experiment browser called MiMiR Online. All requests to access data in MiMiR are routed through a sophisticated middleware security layer thereby allowing secure data access and sharing amongst MiMiR registered users prior to publication. Data in MiMiR can be mined and analysed using the integrated EMAAS open source analysis web portal or via export of data and meta-data into Rosetta Resolver data analysis package.Conclusion: The new MiMiR suite of software enables systematic and effective capture of extensive experimental and clinical information with the highest MIAME score, and secure data sharing prior to publication. MiMiR currently contains more than 150 experiments corresponding to over 3000 hybridisations and supports the Microarray Centre's large microarray user community and two international consortia. The MiMiR flexible and scalable hardware and software architecture enables secure warehousing of thousands of datasets, including clinical studies, from microarray and potentially other -omics technologies

Psychosocial drivers for change: understanding and promoting stakeholder engagement in local adaptation to climate change in three European Mediterranean case studies

Stakeholder engagement in the processes of planning local adaptation to climate change faces many challenges. The goal of this work was to explore whether or not the intention of engaging could be understood (Study 1) and promoted (Study 2), by using an extension of the theory of planned behaviour. In Study 1, stakeholders from three European Mediterranean case studies were surveyed: Baixo Vouga Lagunar (Portugal), SCOT Provence Méditerranée (France), and the island of Crete (Greece) (N = 115). Stakeholders' intention of engaging was significantly predicted by subjective norm (which was predicted by injunctive normative beliefs towards policy-makers and stakeholders) and by perceived behavioural control (which was predicted by knowledge of policy and instruments). Study 2 was conducted in the Baixo Vouga Lagunar case study and consisted of a two-workshop intervention where issues on local and regional adaptation, policies, and engagement were presented and discussed. A within-participants comparison of initial survey results with results following the workshops (NT1 = 12, NT2 = 15, NT3 = 12) indicated that these were successful in increasing stakeholders' intention of engaging. This increase was paired with a) an increase in injunctive normative beliefs towards policy-makers and consequently in subjective norm, and to b) a decrease in perceived complexity of planning local adaptation and an increase in knowledge regarding adaptation to climate change.info:eu-repo/semantics/acceptedVersio

Three-dimensional Noninvasive Monitoring Iodine-131 Uptake in the Thyroid Using a Modified Cerenkov Luminescence Tomography Approach

BACKGROUND: Cerenkov luminescence tomography (CLT) provides the three-dimensional (3D) radiopharmaceutical biodistribution in small living animals, which is vital to biomedical imaging. However, existing single-spectral and multispectral methods are not very efficient and effective at reconstructing the distribution of the radionuclide tracer. In this paper, we present a semi-quantitative Cerenkov radiation spectral characteristic-based source reconstruction method named the hybrid spectral CLT, to efficiently reconstruct the radionuclide tracer with both encouraging reconstruction results and less acquisition and image reconstruction time. METHODOLOGY/PRINCIPAL FINDINGS: We constructed the implantation mouse model implanted with a 400 µCi Na(131)I radioactive source and the physiological mouse model received an intravenous tail injection of 400 µCi radiopharmaceutical Iodine-131 (I-131) to validate the performance of the hybrid spectral CLT and compared the reconstruction results, acquisition, and image reconstruction time with that of single-spectral and multispectral CLT. Furthermore, we performed 3D noninvasive monitoring of I-131 uptake in the thyroid and quantified I-131 uptake in vivo using hybrid spectral CLT. Results showed that the reconstruction based on the hybrid spectral CLT was more accurate in localization and quantification than using single-spectral CLT, and was more efficient in the in vivo experiment compared with multispectral CLT. Additionally, 3D visualization of longitudinal observations suggested that the reconstructed energy of I-131 uptake in the thyroid increased with acquisition time and there was a robust correlation between the reconstructed energy versus the gamma ray counts of I-131 (r(2) = 0.8240). The ex vivo biodistribution experiment further confirmed the I-131 uptake in the thyroid for hybrid spectral CLT. CONCLUSIONS/SIGNIFICANCE: Results indicated that hybrid spectral CLT could be potentially used for thyroid imaging to evaluate its function and monitor its treatment for thyroid cancer

External Ocular Surface Bacterial Isolates and their Antimicrobial Susceptibility Patterns among Pre-operative Cataract Patients at Mulago National Hospital in Kampala, Uganda.

Endophthalmitis is a severe complication of cataract surgery which leads to high ocular morbidity and visual loss even with antibiotic treatment. Bacterial ocular floras are the implicated causative agents. This study was undertaken to evaluate the external ocular surface bacterial isolates and their antimicrobial susceptibility patterns among pre-operative cataract patients at Mulago National Hospital. This cross sectional study enrolled consecutively 131 patients scheduled for routine cataract surgery in the Department of Ophthalmology at Mulago National Hospital in Kampala, Uganda. Eyelid margin and conjunctival swabs were collected and processed using standard microbiological procedures to identify bacterial isolates and their respective antimicrobial susceptibility patterns. Of 131 patients involved (mean age 63.3 ± 14.5 years), 54.2% (71/131) were females. The eyelid margin and conjunctival samples were culture positive in 59.5% (78/138) and 45.8% (60/138) respectively. The most common organisms identified were Coagulase-negative Staphylococci (CoNS) [65.9% (91/138)] and Staphylococcus aureus [21.0% (29/138)]. CoNS showed the highest resistance to tetracycline (58.2%, 53/91) and erythromycin (38.5%, 35/91), whereas in S. aureus the resistance to tetracycline and erythromycin were 55.2% (16/29) and 31.0% (9/29) respectively. Methicillin resistant CoNS (MRS) and Methicillin resistance S. aureus (MRSA) were 31.9% (29/91) and 27.6% (8/29) respectively. There were low resistance rates for CoNS, S. aureus and other bacterial isolates to ciprofloxacin (11.1%-24.2%), gentamicin (5.6-31.0%), tobramycin (17.2% -25.3%) and vancomycin (0.0%). CoNS and S. aureus are the most common bacterial isolates found on the external ocular surface of the pre-operative cataract patients. Ciprofloxacin, gentamicin, tobramycin and vancomycin showed the lowest resistance rates to all bacterial isolates, therefore may be used to reduce bacteria load in the conjunctiva sac among cataract patients prior to surgery

Climate change and cultural heritage : a landscape vulnerability framework

This paper proposes a new framework for calculating vulnerability indices within archaeological resource management on a landscape-scale. Current approaches consider archaeological sites in isolation from their context within the historic landscape. The new framework advocated in this article assesses the vulnerability of landscape character areas, as defined through historic landscape characterisation. This framework uses a two-step vulnerability index: the first assesses the vulnerability of archaeological sites and landscape features; the second uses the results of the first vulnerability index, as well as spatial data on the landscape character areas and the threat in question to calculate the vulnerability of each landscape character area. The framework is applied to a brief case study in coastal North Wales, UK

Articulated Whole-Body Atlases for Small Animal Image Analysis: Construction and Applications

Bone and mineral researc