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    ABSTRACT: Conventionally, myofibrillar protein synthesis is measured over time periods of hours. In clinical studies, interventions occur over weeks. Functional measures over such periods may be more representative. We aimed to develop a novel method to determine myofibrillar protein fractional synthetic rate (FSR) to estimate habitual rates, while avoiding intravenous tracer infusions. Four healthy males were given 100 g water enriched to 70 Atom % with (2) H2 O as a single oral bolus. Vastus-lateralis needle biopsies were performed and plasma samples collected, 3-13 days post-dose. (2) H enrichment in body water was measured in plasma using continuous flow isotope ratio mass spectrometry (IRMS). Myofibrillar protein was isolated from muscle biopsies and acid hydrolysed. (2) H enrichment of protein-bound and plasma-free alanine was measured by gas chromatography (GC)/pyrolysis/IRMS. Myofibrillar protein FSR was calculated (% day(-1) ). The tracer bolus raised the initial enrichment of body water to 1514 ppm (2) H excess. Water elimination followed a simple exponential. The average elimination half-time was 8.3 days. Plasma alanine, labelled during de novo synthesis, followed the same elimination kinetics as water. The weighted average myofibrillar protein FSR from the four subjects was 1.38 % day(-1) (range, 1.0-1.9 % day(-1) ). Myofibrillar protein FSR was measured in free-living healthy individuals over 3-13 days. Using a single oral (2) H2 O bolus, endogenous labelling of alanine occurred in a predictable manner giving estimates of synthesis comparable with published values. Furthermore, the protocol does not compromise the ability to measure other important metabolic processes such as total energy expenditure. Copyright © 2013 John Wiley & Sons, Ltd.
    Rapid Communications in Mass Spectrometry 08/2013; 27(15):1769-1777.
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    ABSTRACT: We have used a simple binomial model of stochastic transgene inactivation at the level of the chromosome or transgene, rather than the cellular level, for the analysis of two mouse transgenic lines that show variegated patterns of expression. This predicts the percentages of cells that express one, both or neither alleles of the transgene in homozygotes from the observed percentages of cells, which express the transgene in hemizygotes. It adequately explained the relationship between the numbers of cells expressing the transgene in hemizygous and homozygous mosaic 21OH/LacZ mouse adrenals and mosaic BLG/7 mouse mammary glands. The binomial model also predicted that a small proportion of cells in mosaic mammary glands of BLG/7 homozygotes would express both BLG/7 alleles but published data indicated that all cells expressing the transgene showed monoallelic expression. Although it didn't fit all of the BLG/7 data as precisely as a more complex model, which used several ad hoc assumptions to explain these results, the simple binomial model was able to explain the relationship in observed transgene expression frequencies between hemizygous and homozygous mosaic tissues for both 21OH/LacZ and BLG/7 mice. It may prove to be a useful general model for analysing other transgenic animals showing mosaic transgene expression.
    Transgenic Research 07/2013;
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    ABSTRACT: Skeletal muscle loss appears to be the most significant clinical event in cancer cachexia and is associated with a poor outcome. With regards to such muscle loss, despite extensive study in a range of models, there is ongoing debate as to whether a reduction in protein synthesis, an increase in degradation or a combination of both is the more relevant. Each model differs in terms of key mediators and the pathways activated in skeletal muscle. Certain models do suggest that decreased synthesis accompanied by enhanced protein degradation via the ubiquitin proteasome pathway (UPP) is important. Murine models tend to involve rapid development of cachexia and may represent more acute muscle atrophy rather than the chronic wasting observed in humans. There is a paucity of human data both at a basic descriptive level and at a molecular/mechanism level. Progress in treating the human form of cancer cachexia can only move forwards through carefully designed large randomised controlled clinical trials of specific therapies with validated biomarkers of relevance to underlying mechanisms.
    The international journal of biochemistry & cell biology 06/2013;
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    ABSTRACT: The type and location of deep digital flexor tendon (DDFT) lesions may be important in predicting outcome. The objectives of this study were to determine the frequency of different types of DDFT lesions within the hoof capsule and to determine whether lesion type predicts return to athletic activity. Lesions of the DDFT were divided into: core lesions, dorsal border lesions and parasagittal splits. Lesion location was documented, and follow-up information was obtained by telephone survey at least 18 months after diagnosis. Of 168 horses with primary DDFT injury, 54 horses had dorsal border lesions, 59 had parasagittal splits and 55 had core lesions. Twenty-five per cent of all horses returned to previous levels of athletic activity within 18 months of MRI evaluation. Horses with complete splits or core lesions of the DDFT were significantly less likely to return to some level of athletic activity than horses with dorsal border lesions P<0.001. Dorsal border lesions of the DDFT appear to have a better prognosis than core lesions or parasagittal splits. This study provides additional information that may help clinicians predict the prognosis for different types of DDFT injury.
    The Veterinary record. 06/2013;
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    ABSTRACT: OBJECTIVES: Blood gas analysis is a well-recognized method to monitor pulmonary function, blood oxygenation, ventilation and acid-base status during general anaesthesia. The aim of this study was to report blood gas analysis results in pet rabbits (Oryctolagus cuniculus) obtained during general anaesthesia using a portable clinical analyser. METHODS: Thirty-two rabbits were premedicated with 0·2 mL/kg fentanyl and fluanisone. Anaesthesia was induced with 0·2 mg/kg midazolam and maintained with 2% isoflurane in oxygen via endotracheal tube. Arterial blood samples were taken from the central ear artery 10 minutes after induction of anaesthesia. RESULTS: Respiratory acidaemia was observed during anaesthesia. Mean ±sd (range) arterial blood pH was 7·33 ±0·08 (7·15 to 7·48). PaCO2 and PaO2 were, respectively, 55·02 ±10·5 (37·7 to 92·1) mmHg and 370·0 ±120·5 (67 to 561) mmHg. Base excess was 2·8 ±3·6 (-3 to 11) mmol/L, HCO3 was 28·73 ±3·07 (23·7 to 35·4) mmol/L and TCO2 was 30·4 ±3·2 (25 to 37) mmol/L. None of the rabbits developed haematoma during arterial blood collection or ischaemia of the pinna during the hospitalization period. CLINICAL SIGNIFICANCE: Arterial blood gas analysis is a safe and easy to perform diagnostic technique that can contribute to improved safety of rabbit anaesthesia, by providing information on the respiratory and metabolic status of the patient.
    Journal of Small Animal Practice 05/2013;
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    ABSTRACT: Background The United Arab Emirates is a rapidly developing country with recent expansion in construction and manufacturing.AimsTo investigate the occurrence and outcomes following occupational traumatic brain injury (TBI) requiring hospital admission.Methods Records for all TBI cases admitted to an Abu Dhabi hospital between 2005 and 2009 were reviewed. Data on mechanisms of occupational injuries, Glasgow Coma Scale (GCS) on admission and Glasgow Outcome Scale (GOS) on follow-up, were analysed.ResultsOf 581 TBI cases reviewed, 56 (10%) cases were reported as occupational by either the patient or the informant accompanying the patient. All cases were male migrants, and 63% were aged 25-44. Falls accounted for 63% of cases, falling objects 34% and motor vehicle collisions 4%. Median GCS score was 13 for all cases. Median hospital stay was 7.5 days. Intensive care unit admission data were available in 47 cases, of which 34% (16) were admitted with a median stay of 5 days. GOS data were available in 95% (53) of cases, with good recovery in 81% cases, moderate-to-severe disability in 11% of cases and death in 8% (4) cases.Conclusions Occupational TBI requiring hospitalization is most frequently due to falls and falling objects, with potentially grave consequences. This study further highlights the urgent need to implement preventative measures to improve construction worker safety.
    Occupational Medicine 04/2013;
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    ABSTRACT: OBJECTIVES: Delirium is associated with an increased risk of long-term cognitive decline, suggesting the possibility of concurrent central nervous system (CNS) injury. S100B is a putative biomarker of CNS injury and elevated serum levels in delirium have been reported. Here we hypothesize that delirium is associated with raised concentrations of cerebrospinal fluid (CSF) S100B. METHODS: Forty-five patients with hip fracture aged over 60 and awaiting surgery under spinal anesthesia were assessed for delirium pre- and post-operatively. CSF S100B levels were measured in samples collected at the onset of surgery. RESULTS: Participants with pre-operative delirium (N = 8) had elevated Log10 CSF S100B (mean: -0.156; SD: 0.238) compared with those without delirium (mean: -0.306; SD: 0.162), Student's t-test t = 2.18, df = 43, p = 0.035. CONCLUSIONS: This study provides preliminary evidence of elevated CSF S100B in current delirium, consistent with findings in serum and with other studies showing elevated S100B in the presence of diverse forms of CNS injury.
    The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 04/2013;
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    ABSTRACT: The past 20 years have witnessed a dramatic resurgence of interest in a hitherto obscure neurodegenerative disease, Creutzfeldt-Jakob disease (CJD). This was driven partly by the novelty of the prion hypothesis, which sought to provide an explanation for the pathogenesis of transmissible spongiform encephalopathies, involving a unique epigenetic mechanism, and partly by events in the UK, where an outbreak of a new prion disease in cattle (bovine spongiform encephalopathy or BSE) potentially exposed a large section of the UK population to prion infectivity through a dietary route. The numbers of cases of the resultant novel disease variant CJD (vCJD), have so far been limited and peaked in the UK in the year 2000 and have subsequently declined. However, the effects of BSE and vCJD have been far-reaching. The estimated prevalence of vCJD infection in the UK is substantially higher than the numbers of clinical cases would suggest, posing a difficult dilemma for those involved in blood transfusion, tissue transplantation and cellular therapies. The clinico-pathological phenotype of human prion diseases has come under close scrutiny and molecular classification systems have been developed to account for the different diseases and their phenotypic spectra. Moreover, enhanced human and animal surveillance and better diagnostic tools have identified new human and animal prion diseases. Lastly, as the prion hypothesis has gained widespread acceptance, the concepts involved have been applied to other areas, including extra-chromosomal inheritance in fungi, long-term potentiation in memory formation and the spread of molecular pathology in diverse conditions, such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Studies at the molecular and cellular level have helped to provide a better understanding of human prion diseases, aided pathological diagnosis and helped inform public health decision-making.
    Neuropathology 01/2013;
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    ABSTRACT: Standard univariate analyses of brain imaging data have revealed a host of structural and functional brain alterations in schizophrenia. However, these analyses typically involve examining each voxel separately and making inferences at group-level, thus limiting clinical translation of their findings. Taking into account the fact that brain alterations in schizophrenia expand over a widely distributed network of brain regions, univariate analysis methods may not be the most suited choice for imaging data analysis. To address these limitations, the neuroimaging community has turned to machine learning methods both because of their ability to examine voxels jointly and their potential for making inferences at a single-subject level. This article provides a critical overview of the current and foreseeable applications of machine learning, in identifying imaging-based biomarkers that could be used for the diagnosis, early detection and treatment response of schizophrenia, and could, thus, be of high clinical relevance. We discuss promising future research directions and the main difficulties facing machine learning researchers as far as their potential translation into clinical practice is concerned.
    NeuroImage. Clinical. 01/2013; 3:279-289.
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    ABSTRACT: Cerebral cavernous malformations (CCMs) and arteriovenous malformations (AVMs) are common: their asymptomatic prevalence on brain magnetic resonance imaging (MRI) is 1 in 625 and 1 in 2,000, respectively. The risk of epileptic seizure(s) for people with AVMs and CCMs affects their domestic, social, and professional lives, and may influence their decisions about treatment. This article summarizes the seizure risks for people with AVMs and CCMs, gleaned from published original articles indexed in OVID Medline and Embase before 1 January 2012. In the absence of prior intracranial hemorrhage and nonhemorrhagic focal neurologic deficit, a population-based study in Scotland, United Kingdom, found that the 5-year risks of first seizure were 8% for AVM and 4% for CCM; presentation with intracranial hemorrhage or focal neurologic deficit raised this risk for AVM (23%) but not for CCM (6%). Features associated with the occurrence of epileptic seizures for CCM are lesion multiplicity and cortical CCM location, whereas for AVM the most consistently reported associations are younger age, temporal location, cortical involvement, and nidus diameter >3 cm. In the absence of prior intracranial hemorrhage and nonhemorrhagic focal neurologic deficit, the 5-year risk of developing epilepsy following a first seizure is 58% for AVM and 94% for CCM, though there is no difference in the chance of achieving 2-year seizure freedom in this time frame (45% AVM vs. 47% CCM). Observational case series describe encouraging differences in seizure frequency before and after AVM and CCM treatment, but the shortage of studies demonstrating dramatic effects in comparison to concurrent control groups justifies the need for more controlled studies, ideally with randomized treatment allocation when the benefits of AVM or CCM treatment are uncertain.
    Epilepsia 09/2012; 53 Suppl 4:34-42.
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