Use of 1H and 31P HRMAS to evaluate the relationship between quantitative alterations in metabolite concentrations and tissue features in human brain tumour biopsies

[EN] Quantitative multinuclear high-resolution magic angle spinning (HRMAS) was performed in order to determine the tissue pH values of and the absolute metabolite concentrations in 33 samples of human brain tumour tissue. Metabolite concentrations were quantified by 1D 1 H and 31P HRMAS using the electronic reference to in vivo concentrations (ERETIC) synthetic signal. 1 H–1 H homonuclear and 1 H–31P heteronuclear correlation experiments enabled the direct assessment of the 1 H–31P spin systems for signals that suffered from overlapping in the 1D 1 H spectra, and linked the information present in the 1D 1 H and 31P spectra. Afterwards, the main histological features were determined, and high heterogeneity in the tumour content, necrotic content and nonaffected tissue content was observed. The metabolite profiles obtained by HRMAS showed characteristics typical of tumour tissues: rather low levels of energetic molecules and increased concentrations of protective metabolites. Nevertheless, these characteristics were more strongly correlated with the total amount of living tissue than with the tumour cell contents of the samples alone, which could indicate that the sampling conditions make a significant contribution aside from the effect of tumour development in vivo. The use of methylene diphosphonic acid as a chemical shift and concentration reference for the 31P HRMAS spectra of tissues presented important drawbacks due to its interaction with the tissue. Moreover, the pH data obtained from 31P HRMAS enabled us to establish a correlation between the pH and the distance between the N(CH3)3 signals of phosphocholine and choline in 1 H spectra of the tissue in these tumour samples.The authors acknowledge the SCSIE-University of Valencia Microscopy Service for the histological preparations. They also acknowledge Martial Piotto (Bruker BioSpin, France) for providing the ERETIC synthetic signal. Furthermore, they acknowledge financial support from the Spanish Government project SAF2007-6547, the Generalitat Valenciana project GVACOMP2009-303, and the E.U.'s VI Framework Programme via the project "Web accessible MR decision support system for brain tumor diagnosis and prognosis, incorporating in vivo and ex vivo genomic and metabolomic data" (FP6-2002-LSH 503094). CIBER-BBN is an initiative funded by the VI National R&D&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions, and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund.Esteve Moya, V.; Celda, B.; Martínez Bisbal, MC. (2012). Use of 1H and 31P HRMAS to evaluate the relationship between quantitative alterations in metabolite concentrations and tissue features in human brain tumour biopsies. 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Healthcare-associated infections including neonatal blood stream infections in a leading tertiary hospital in Botswana

Background: Healthcare-associated infections (HAIs) increase morbidity, mortality, length of hospital stay and costs, and should be prevented where possible. In addition, up to 71% of neonates are prone to bloodstream infections (BSI) during intensive care due to a variety of factors. Consequently, the objectives of this study were to estimate the burden of HAIs and possible risk factors in a tertiary hospital in Botswana as well as describe current trends in bacterial isolates from neonatal blood specimen and their antibiotic resistance patterns.Methods: Point Prevalence Survey (PPS) in all hospital wards and a retrospective cross-sectional review of neonatal blood culture and sensitivity test results, with data abstracted from the hospital laboratory database.Results: 13.54% (n = 47) of patients had HAIs, with 48.9% (n = 23) of them lab-confirmed. The highest prevalence of HAIs was in the adult intensive care unit (100% - n = 5), the nephrology unit (50% - n = 4), and the neonatal intensive care unit (41.9% - n = 13). One-fourth of HAIs were site unspecific, 19.1% (n = 9) had surgical site infections (SSIs), 17% (n = 8) ventilator-associated pneumonia/complications, and 10.6% (n = 5) were decubitus ulcer infections. There were concerns with overcrowding in some wards and the lack of aseptic practices and hygiene. These issues are now being addressed through a number of initiatives. Coagulase Negative Staphylococci (CoNS) was the commonest organism (31.97%) isolated followed by Enterococci spp. (18.03%) among neonates. Prescribing of third-generation cephalosporins is being monitored to reduce Enterococci, Pseudomonas and Acinetobacter spp. infections.Conclusions: There were concerns with the rate of HAIs and BSIs. A number of initiatives are now in place in the hospital to reduce these including promoting improved infection prevention and control (IPC) practices and use of antibiotics via focal persons of the multidisciplinary IPC committee. These will be followed up and reported on

On the Design of a Web-Based Decision Support System for Brain Tumour Diagnosis Using Distributed Agents

This paper introduces HealthAgents, an EC-funded research project to improve the classification of brain tumours through multi-agent decision support over a distributed network of local databases or Data Marts. HealthAgents will not only develop new pattern recognition methods for a distributed classification and analysis of in vivo MRS and ex vivo/in vitro HRMAS and DNA data, but also define a method to assess the quality and usability of a new candidate local database containing a set of new cases, based on a compatibility score

Dynamic Cardiolipin Synthesis Is Required for CD8⁺ T Cell Immunity

Mitochondria constantly adapt to the metabolic needs of a cell. This mitochondrial plasticity is critical to T cells, which modulate metabolism depending on antigen-driven signals and environment. We show here that de novo synthesis of the mitochondrial membrane-specific lipid cardiolipin maintains CD8+ T cell function. T cells deficient for the cardiolipin-synthesizing enzyme PTPMT1 had reduced cardiolipin and responded poorly to antigen because basal cardiolipin levels were required for activation. However, neither de novo cardiolipin synthesis, nor its Tafazzin-dependent remodeling, was needed for T cell activation. In contrast, PTPMT1-dependent cardiolipin synthesis was vital when mitochondrial fitness was required, most notably during memory T cell differentiation or nutrient stress. We also found CD8+ T cell defects in a small cohort of patients with Barth syndrome, where TAFAZZIN is mutated, and in a Tafazzin-deficient mouse model. Thus, the dynamic regulation of a single mitochondrial lipid is crucial for CD8+ T cell immunity

Multiproject–multicenter evaluation of automatic brain tumor classification by magnetic resonance spectroscopy

Contains fulltext : 75361.pdf (publisher's version ) (Open Access)14 p

ICAR: endoscopic skull‐base surgery

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Agent-Based Distributed Decision Support System for Brain Tumour Diagnosis and Prognosis

Brain tumours remain an important cause of morbidity and mortality in Europe. Diagnosis using Magnetic Resonance Imaging (MRI) is non-invasive, but only achieves 60-90% accuracy depending on the tumour type and grade. The current gold standard classification of brain tumours by biopsy and histopathological analysis involves invasive surgical procedure and incurs a risk. Nowadays the diagnosis and treatment of brain tumours is typically based on clinical symptoms, radiological appearance and often a histopathological diagnosis of a biopsy. However, treatment response of histologically or radiologically-similar tumours can vary widely, particularly in children. Magnetic Resonance Spectroscopy (MRS) is a non-invasive technique for determining the tissue biochemical composition (metabolomic profile) of a tumour. Additionally, the genomic profile, determined using DNA microarrays, facilitates the classification of tumour grades and types not trivially distinguished by morphologic appearance. Thus, we propose the definition of a decision support system (DSS) which employs MRS and genomic profiles. This DSS will deploy an ad hoc agent-based architecture in order to negotiate a distributed diagnostic tool for brain tumours, implement data mining techniques, transfer clinical data and extract information. The distributed nature of our approach will help the users to observe local centre policies for sharing information whilst allowing them to benefit from the use of distributed data warehouse (d-DWH). Moreover, it will permit the design of local classifiers targeting a specific patient population. We argue that this new information for classifying tumours along with clinical data, should be securely and easy accessible in order to improve the diagnosis and prognosis of tumours. All data will be stored anonymously, and securely through a network of data marts based on all this information acquired and stored at centres throughout Europe. This network will grant bona-fide access to an organisation in return for its contribution of clinical data to a d-DWH/Decision Support System (d-DSS). This rest of this paper is structured as follows. First, we provide some background on the underlying technologies for this project: brain tumour detection and agent technology. Then we provide the architectural specification. Finally, we conclude with our future work

Identifying constituent tumor tissues subclasses in HR-MAS spectra using advanced blind source separation techniques

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Quantifying brain tumor tissue abundance in HR-MAS spectra using non-negative blind source separation techniques

Given high-resolution magic angle spinning (HR-MAS) spectra from several glial tumor subjects, our goal is to differentiate between tumor tissue types by separating the different sources that contribute to the profile of each spectrum. Blind source separation techniques are applied for obtaining characteristic profiles for necrosis, highly cellular tumor and border tumor tissue and providing the contribution (abundance) of each of these tumor tissue types to the profile of each spectrum. The problem is formulated as a non-negative source separation problem. Non-negative matrix factorization, convex analysis of non-negative sources and non-negative independent component analysis methods are considered. The results are in agreement with the pathology obtained by the histopathological examination that succeeded the HR-MAS measurements. Furthermore, an analysis to verify to which extent the dimension of the input space, the input features and the number of sources to be extracted from the HR-MAS data could influence the performance of the source separation is presented. © 2012 John Wiley & Sons, Ltd.status: publishe