Additives and Protein-DNA Combinations Modulate the Humoral Immune Response Elicited by a Hepatitis C Virus Core-encoding Plasmid in Mice

Humoral and cellular immune responses are currently induced against hepatitis C virus (HCV) core following vaccination with core-encoding plasmids. However, the anti-core antibody response is frequently weak or transient. In this paper, we evaluated the effect of different additives and DNA-protein combinations on the anti-core antibody response. BALB/c mice were intramuscularly injected with an expression plasmid (pIDKCo), encoding a C-terminal truncated variant of the HCV core protein, alone or combined with CaCl2, PEG 6000, Freund's adjuvant, sonicated calf thymus DNA and a recombinant core protein (Co.120). Mixture of pIDKCo with PEG 6000 and Freund's adjuvant accelerated the development of the anti-core Ab response. Combination with PEG 6000 also induced a bias to IgG2a subclass predominance among anti-core antibodies. The kinetics, IgG2a/IgG1 ratio and epitope specificity of the anti-core antibody response elicited by Co.120 alone or combined with pIDKCo was different regarding that induced by the pIDKCo alone. Our data indicate that the antibody response induced following DNA immunization can be modified by formulation strategies.

Core Functions of the Health Service Report

The Government Decision1 on the Structural, Organisational, Financial Management and Systems Reform of the Health Sector of June, 2003 acknowledged that in order to increase the effectiveness of the health service generally, and its capacity to deliver the reform agenda, it was important that the service was fully concentrated on addressing its core health objectives. The Minister for Health and Children and Minister for Finance felt that there could be scope to transfer certain functions out of the health service and locate them more appropriately within other functional areas of Government. As part of the overall decision, it was agreed that a working group would be established, to include the Departments of Health and Children, Finance and An Taoiseach, to examine the scope for transfer of certain activities to other, more appropriate, Departments and agencies and that on completion of this review, the Minister for Health and Children would bring proposals to Government. Read the Report (PDF, 70kb)  

Optimització d'una aplicació bioinformàtica d'aliniament de seqüències executada en processadors many-core (GPUs)

Las herramientas de análisis de secuencias genómicas permiten a los biólogos identificar y entender regiones fundamentales que tienen implicación en enfermedades genéticas. Actualmente existe una necesidad de dotar al ámbito científico de herramientas de análisis eficientes. Este proyecto lleva a cabo una caracterización y análisis del rendimiento de algoritmos utilizados en la comparación de secuencias genómicas completas, y ejecutadas en arquitecturas MultiCore y ManyCore. A partir del análisis se evalúa la idoneidad de este tipo de arquitecturas para resolver el problema de comparar secuencias genómicas. Finalmente se propone una serie de modificaciones en las implementaciones de estos algoritmos con el objetivo de mejorar el rendimiento.

Optimització d'una aplicacio bioinformàtica d'alineament de seqüències executada en processadors multi-core i many-core (GPUs)

Las aplicaciones de alineamiento de secuencias son una herramienta importante para la comunidad científica. Estas aplicaciones bioinformáticas son usadas en muchos campos distintos como pueden ser la medicina, la biología, la farmacología, la genética, etc. A día de hoy los algoritmos de alineamiento de secuencias tienen una complejidad elevada y cada día tienen que manejar un volumen de datos más grande. Por esta razón se deben buscar alternativas para que estas aplicaciones sean capaces de manejar el aumento de tamaño que los bancos de secuencias están sufriendo día a día. En este proyecto se estudian y se investigan mejoras en este tipo de aplicaciones como puede ser el uso de sistemas paralelos que pueden mejorar el rendimiento notablemente.

Astrocyte dense-core vesicle gliosecretion is governed by rest/nrsf

Astrocytes are the brain non-nerve cells competent for the expression of clear and dense-core vesicles (DCVs) and for their regulated exocytosis. This process, called gliosecretion, nearly resembles the neurosecretion occurring in neurons and neurosecretory cells. REST/NRSF is a transcription repressor known to orchestrate nerve-cell differentiation, governing the expression of hundreds of neuron-specific genes through their repression in the non-nerve and their fine modulation in the nerve cells. Our previous studies in neurosecretory rat PC12 cells identified REST as the critical factor for the expression not only of individual genes, but also of the whole neurosecretory process via multiple, direct and indirect mechanisms (D'Alessandro et al., J. Neurochem., 2008; Klajn et al., J. Neurosci., 2009). Therefore we wondered whether gliosecretion was governed by REST. We investigated rat astrocyte primary cultures: they exhibited high REST, which directly represses the transcription of at least one target gene, and expressed neither DCVs nor their markers (granins, peptides, membrane proteins). Transfection of a dominant-negative construct of REST (REST/ DBD-GFP) induced the appearance of DCVs filled with secretogranin2 and NPY that are distinct from other intracellular organelles. TIRF analysis of astrocytes co-transfected with REST/DBD-GFP and NPY-mRFP constructs revealed NPY-mRFP-positive DCVs undergoing Ca2þ-dependent exocytosis, largely prevented by BoNT/B. Immunohistochemistry of the I-II layers of the human temporal brain cortex showed all neurons and microglia exhibiting the expected inappreciable and high levels of REST, respectively. In contrast astrocyte RESTwas variable, going from inappreciable to high, accompanied by variable expression of DCVs. In this work it has been demonstrated that astrocyte DCV expression and gliosecretion are governed by REST (Prada et al., 2011 in press). The variable in situ REST levels may contribute to the well known structural/functional heterogeneity of astrocytes and this new observation might be of great interest for the understanding of both astrocyte physiology and pathology.

Ultra-high pressure liquid chromatography-mass spectrometry for plant metabolomics: a systematic comparison of high-resolution quadrupole-time-of-flight and single stage Orbitrap mass spectrometers.

The response of Arabidopsis to stress caused by mechanical wounding was chosen as a model to compare the performances of high resolution quadrupole-time-of-flight (Q-TOF) and single stage Orbitrap (Exactive Plus) mass spectrometers in untargeted metabolomics. Both instruments were coupled to ultra-high pressure liquid chromatography (UHPLC) systems set under identical conditions. The experiment was divided in two steps: the first analyses involved sixteen unwounded plants, half of which were spiked with pure standards that are not present in Arabidopsis. The second analyses compared the metabolomes of mechanically wounded plants to unwounded plants. Data from both systems were extracted using the same feature detection software and submitted to unsupervised and supervised multivariate analysis methods. Both mass spectrometers were compared in terms of number and identity of detected features, capacity to discriminate between samples, repeatability and sensitivity. Although analytical variability was lower for the UHPLC-Q-TOF, generally the results for the two detectors were quite similar, both of them proving to be highly efficient at detecting even subtle differences between plant groups. Overall, sensitivity was found to be comparable, although the Exactive Plus Orbitrap provided slightly lower detection limits for specific compounds. Finally, to evaluate the potential of the two mass spectrometers for the identification of unknown markers, mass and spectral accuracies were calculated on selected identified compounds. While both instruments showed excellent mass accuracy (<2.5ppm for all measured compounds), better spectral accuracy was recorded on the Q-TOF. Taken together, our results demonstrate that comparable performances can be obtained at acquisition frequencies compatible with UHPLC on Q-TOF and Exactive Plus MS, which may thus be equivalently used for plant metabolomics.

Director of Public Health Annual Report 2010 and associated core tables 2009

Thissecond annual report of the Director of Public Health highlights the many public health challenges that affect people in Northern Ireland. It demonstrates how the public health team tackles this complex agenda by working with many statutory, community and voluntary partner organisations across health, local government, education, housing and other sectors. It shows a wealth of innovative work to address the main public health challenges facing communities, health inequality, preventing and protecting against ill-health, detecting illness early, and providing high quality services. Integral to thereport are core tables for 2009 which provide key statistical data on population, birth and death rates, mortality by cause, life expectancy, immunisation and screening.

Fast analysis of doping agents in urine by ultra-high-pressure liquid chromatography-quadrupole time-of-flight mass spectrometry. II: Confirmatory analysis.

For doping control, analyses of samples are generally achieved in two steps: a rapid screening and, in the case of a positive result, a confirmatory analysis. A two-step methodology based on ultra-high-pressure liquid chromatography coupled to a quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) was developed to screen and confirm 103 doping agents from various classes (e.g., beta-blockers, stimulants, diuretics, and narcotics). The screening method was presented in a previous article as part I (i.e., Fast analysis of doping agents in urine by ultra-high-pressure liquid chromatography-quadrupole time-of-flight mass spectrometry. Part I: screening analysis). For the confirmatory method, basic, neutral and acidic compounds were extracted by a dedicated solid-phase extraction (SPE) in a 96-well plate format and detected by MS in the tandem mode to obtain precursor and characteristic product ions. The mass accuracy and the elemental composition of precursor and product ions were used for compound identification. After validation including matrix effect determination, the method was considered reliable to confirm suspect results without ambiguity according to the positivity criteria established by the World Anti-Doping Agency (WADA). Moreover, an isocratic method was developed to separate ephedrine from its isomer pseudoephedrine and cathine from phenylpropanolamine in a single run, what allowed their direct quantification in urine.

Eating disorders: Core interventions in the treatment and management of anorexia nervosa, bulimia nervosa and related eating disorders

Core interventions in the treatment and management of anorexia nervosa, bulimia nervosa and related eating disorders - NICE Guidance

Standard Evaluation Framework for Weight Management Interventions - Core Criteria

The National Obesity Observatory was established to provide a single point of contact for wide-ranging authoritative information on data and evidence related to obesity, overweight, underweight and their determinants. The Standard Evaluation Framework is a list of data collection criteria and supporting guidance for collecting high quality information to support the evaluation of weight management interventions. This is a quick reference guide to the core criteria of the Standard Evaluation Framework. Essential criteria are presented as the minimum recommended data for evaluating a weight management intervention. Desirable criteria are additional data that would enhance the evaluation.refer to the resource

Hepatitis B virus screening in contacts of blood donors with antibodies against core protein (anti-HBc), but without surface antigen (HBsAg)

To increase blood safety Brazil introduced screening for anti-HBc among blood donors in 1993. There was a decrease in the hepatitis B virus (HBV) transmission, but this measure identified a great number of HBsAg-negative, anti-HBc-positive donors. Surveillance policy determines that contacts of HBV carriers should be screened to HBV markers, but there is no recommendation about how to guide contacts of HBsAg-negative, anti-HBc-positive donors. Aiming to evaluate whether the contacts of this group are at greater risk for HBV infection, a cross-sectional study was performed to compare prevalence of HBV infection between contacts of HBsAg-positive blood donors (group I) and contacts of HBsAg-negative, anti-HBc-positive donors (group II). Contacts were submitted to a questionnaire and blood tests for HBV markers. In group I (n = 143), 53 (37.1%) were anti-HBc-positive and 11 (7.7%) were HBsAg-positive. In group II (n = 111), there were 9 and 0.9%, respectively. HBV exposure was associated with group I, sexual activity, blood transfusion, being one of the donor's parents, and living for more than ten years with the donor. Regarding the families as sample units, it was more common to find at least one member with HBV markers (p < 0.05) among the families of group I compared to group II. Contacts of HBsAg-negative, anti-HBc-positive individuals presented a much lower risk of having already been exposed to HBV and there is no need to screen them for HBV in low to moderate prevalence populations.

Deep accidental hypothermia with core temperature below 24°c presenting with vital signs.

Abstract Pasquier, Mathieu, Noemi Zurron, Barbara Weith, Pierre Turini, Fabrice Dami, Pierre-Nicolas Carron, and Peter Paal. Deep accidental hypothermia with core temperature below 24°C presenting with vital signs. High Alt Med Biol. 15:58-63, 2014.-Background: According to the Swiss hypothermia clinical staging, patients with stage III are unconscious with preserved vital signs, with core temperature usually between 24° and 28°C. With stage IV, vital signs are absent with core temperature <24°C. Aims: To describe a patient presenting with HT stage III with vital signs but a core temperature of <24°C, and to search for similar patients in the medical literature. Materials and methods: MEDLINE was used to search for cases of deep accidental hypothermia (<24°C) and preserved vital signs. Results: We found 22 cases in addition to our case (n=23). Median age was 44 years (IQR 36; range 4-83) and median core temperature 22°C (IQR 1.7; 17-23.8). Vital signs were often minimal. Seven patients developed ventricular fibrillation (VF). Twenty patients survived with excellent neurological outcome. Conclusions: Vital signs can be present in hypothermic patients with core temperature <24°C. In deeply hypothermic patients, a careful check and prolonged check of vital functions should be made, as vital signs may be minimal. The clinical Swiss staging remains valuable in the prehospital evaluation of hypothermic patients; its correlation with core temperature should be better defined.

Director of Public Health annual report 2011 and core tables 2010

Too many children and young people are living in circumstances that make it difficult for them to thrive. That is the key message from the third Annual Report of the Director of Public Health (DPH) for Northern Ireland, which was published on 14th June 2012. This significant report highlights the many public health challenges that affect people in Northern Ireland.As Director of Public Health, Dr Carolyn Harper's report describes the main public health challenges across Northern Ireland, and details work being undertaken by the Public Health Agency (PHA) and its partners over the past year to improve the health and wellbeing of people here.A Core Tables report for 2010, available below, produced by the PHA in support of the Director of Public Health's Annual Report for 2011-2012, including information such as estimated home population figures and projections, births information, fertility rates, death rates, information on mortality, life expectancy, immunisation rates and screening uptake rates.