The global public health threat of antibiotic-resistant infections as well as the lack of new treatments in clinical development is a critical issue. Reasons for this include diminished commercial incentives for pharmaceutical companies to develop new antibiotics, which part-reflects a shift in antibiotic marketing paradigm from broad deployment to targeted therapy in relatively small patient populations. Such changes are encouraged by antimicrobial stewardship (AMS).
View Article and Find Full Text PDFTranslation initiation is on the critical pathway for the production of monoclonal antibodies (mAbs) by mammalian cells. Formation of a closed loop structure comprised of mRNA, a number of eukaryotic initiation factors (eIFs) and ribosomal proteins has been proposed to aid re-initiation of translation and therefore increase global translational efficiency. We have determined mRNA and protein levels of the key components of the closed loop, eIFs (eIF3a, eIF3b, eIF3c, eIF3h, eIF3i and eIF4G1), poly(A)-binding protein (PABP) 1 and PABP-interacting protein 1 (PAIP1), across a panel of 30 recombinant mAb-producing GS-CHOK1SV cell lines with a broad range of growth characteristics and production levels of a model recombinant mAb.
View Article and Find Full Text PDFOne of the most significant impediments to high-quality EEG recorded in an MRI scanner is subject motion. Availability of motion artifact sensors can substantially improve the quality of the recorded EEG. In the study of epilepsy, it can also dramatically increase the confidence that one has in discriminating true epileptiform activity from artifact.
View Article and Find Full Text PDFTelavancin was the first marketed lipoglycopeptide. Although licensed in Europe in 2011 for the treatment of nosocomial pneumonia caused by meticillin-resistant Staphylococcus aureus (MRSA), it did not become clinically available until March 2014. Given the limited clinical experience with telavancin in Europe, this review provides an overview of its antimicrobial and clinical activity as well as its position among today's antimicrobials, with particular focus on the implications of its licensing requirements.
View Article and Find Full Text PDFThe evidence clearly indicates that a care-bundle approach is needed to prevent catheter-related bloodstream infections (CRBSIs). Such an approach includes the need for education, training and adequate staffing, sterile barrier precautions, skin preparation, use of intravenous dressings and antimicrobial prophylaxis. Care bundles advise which aspects must be given priority and what procedures will produce optimum outcomes.
View Article and Find Full Text PDFEur J Clin Microbiol Infect Dis
December 2014
The demographics of the healthcare population are changing, with an ever-greater proportion of people being treated outside the traditional hospital setting through community healthcare. This shift in the way that healthcare is delivered raises new concerns over community healthcare-associated infections (HCAIs). A literature search between 2000 and December 2013 was conducted in databases including PubMed, SciVerse ScienceDirect and Google Scholar.
View Article and Find Full Text PDFObjective: Lennox-Gastaut syndrome (LGS) is a severe epilepsy phenotype with characteristic electroclinical features despite diverse etiologies. We previously found common cerebral networks involved during slow spike-and-wave (SSW) and generalized paroxysmal fast activity (PFA), characteristic interictal discharges. Some patients have a Lennox-Gastaut-like phenotype and cortical lesions.
View Article and Find Full Text PDFMethicillin-resistant Staphylococcus aureus (MRSA) is an important cause of antimicrobial-resistant hospital-acquired infections worldwide and remains a public health priority in Europe. Nosocomial pneumonia (NP) involving MRSA often affects patients in intensive care units with substantial morbidity, mortality and associated costs. A guideline-based approach to empirical treatment with an antibacterial agent active against MRSA can improve the outcome of patients with MRSA NP, including those with ventilator-associated pneumonia.
View Article and Find Full Text PDFTranslational control is central to the gene expression pathway and was the focus of the 2013 annual Translation UK meeting held at the University of Kent. The meeting brought together scientists at all career stages to present and discuss research in the mRNA translation field, with an emphasis on the presentations on the research of early career scientists. The diverse nature of this field was represented by the broad range of papers presented at the meeting.
View Article and Find Full Text PDFWe report an NMR based approach to determine the metabolic reprogramming of Chinese hamster ovary cells upon a temperature shift during culture by investigating the extracellular cell culture media and intracellular metabolome of CHOK1 and CHO-S cells during culture and in response to cold-shock and subsequent recovery from hypothermic culturing. A total of 24 components were identified for CHOK1 and 29 components identified for CHO-S cell systems including the observation that CHO-S media contains 5.6 times the level of glucose of CHOK1 media at time zero.
View Article and Find Full Text PDFPurpose: Lennox-Gastaut syndrome (LGS) is a severe epileptic disorder with characteristic electroclinical features but diverse etiologies. The shared electroclinical characteristics suggest that common cerebral networks are involved in generating seizures. We sought to reveal these networks by comparing ictal and interictal single-photon emission computed tomography (SPECT).
View Article and Find Full Text PDFBackground: Systemic Candida infections (SCI) occur predominantly in intensive care unit patients and are a common cause of morbidity and mortality. Recently, changes in Candida epidemiology with an increasing prevalence of SCI caused by Candida non-albicans species have been reported. Resistance to fluconazole and azoles in general is not uncommon for non-albicans species.
View Article and Find Full Text PDFIn this study we used EEG-fMRI to investigate whether peri-ventricular nodular heterotopia (PNH) are connected to the seizure generating network in individuals initially diagnosed with absence seizures (AS) who were later found to have co-existent PNH. We performed event related EEG-fMRI of the patients typical events as well as performing functional connectivity (FC) seeded from the PNH to answer this question. Both subjects demonstrated event related BOLD change in the "core" absence network.
View Article and Find Full Text PDFPurpose: The aim of this study was to provide better spatiotemporal description of the brain activity observed during generalized spike-and-wave (GSW) discharges. Simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) studies of these epileptiform events have shown regional differences in the timing of fMRI signal changes, which suggests activities within multiple interacting networks rather than a single unified network.
Methods: EEG-fMRI recordings from eight patients with childhood absence epilepsy (CAE) were studied using event-related independent components analysis (eICA).
Severe and persistent speech disorder, dysarthria, may be present for life after brain injury in childhood, yet the neural correlates of this chronic disorder remain elusive. Although abundant literature is available on language reorganization after lesions in childhood, little is known about the capacity of motor speech networks to reorganize after injury. Here, we examine the structural and functional neural correlates associated with chronic dysarthria after childhood-onset traumatic brain injury.
View Article and Find Full Text PDFMRI provides a powerful tool for studying the functional and structural connections in the brain non-invasively. The technique of functional connectivity (FC) exploits the intrinsic temporal correlations of slow spontaneous signal fluctuations to characterise brain functional networks. In addition, diffusion MRI fibre-tracking can be used to study the white matter structural connections.
View Article and Find Full Text PDFEvent-related analyses of functional MRI (fMRI) typically assume that the onset and offset of neuronal activity match stimuli onset and offset, and that evoked fMRI signal changes follow the canonical haemodynamic response function (HRF). Some event types, however, may be unsuited to this approach: brief stimuli might elicit an extended neuronal response; anticipatory effects might result in activity preceding the event; or altered neurovascular coupling may result in a non-canonical HRF. An example is interictal epileptiform discharges (IEDs), which may show a non-canonical HRF and fMRI signal changes preceding their onset as detected on EEG.
View Article and Find Full Text PDFInfect Control Hosp Epidemiol
August 2012
Objective: To determine the proportion of methicillin-resistant Staphylococcus aureus (MRSA) detections identified by nasal swabbing using agar culture in comparison with multiple body site testing using agar and nutrient broth culture.
Design: Cross-sectional study.
Patients: Adult patients admitted to 36 general specialty wards of 2 large hospitals in Scotland.
Objective: Studies of absence seizures (AS) using EEG with fMRI (EEG-fMRI) show a consistent network with prominent thalamic activation and a variety of cortical changes. Despite evidence suggesting a role of frontal cortex in seizure generation, group studies have not detected consistent AS-related changes in this region. We hypothesized that only a subgroup may show frontal cortical activation.
View Article and Find Full Text PDFPost-influenza bacterial pneumonia is a major cause of morbidity and mortality associated with both seasonal and pandemic influenza virus illness. However, despite much interest in influenza and its complications in recent years, good clinical trial data to inform clinicians in their assessment of treatment options are scant. This paucity of evidence needs to be addressed urgently in order to improve guidance on the management of post-influenza bacterial pneumonia.
View Article and Find Full Text PDFPurpose: Functional imaging studies have identified a common network of brain regions that activate and deactivate during the generalised spike wave (GSW) discharges of childhood absence epilepsy (CAE). Functional connectivity within this network is also altered during the resting state. In this study our aim was to assess functional connectivity throughout the whole brain of patients with CAE.
View Article and Find Full Text PDFBackground: A Health Technology Assessment (HTA) model on effectiveness of meticillin-resistant Staphylococcus aureus (MRSA) screening in Scotland suggested that universal screening using chromogenic agar was the preferred option in terms of effectiveness and cost.
Aim: To test the model's validity through a one-year pilot-study.
Method: A large one-year prospective cohort study of MRSA screening was carried out in six acute hospitals in NHS Scotland, incorporating 81,438 admissions.
Objective: To estimate the proportion of patients who acquire methicillin-resistant Staphylococcus aureus (MRSA) while in hospital and to identify risk factors associated with acquisition of MRSA.
Design: Retrospective cohort study.
Patients: Adult patients discharged from 36 general specialty wards of 2 Scottish hospitals that had implemented universal screening for MRSA on admission.