Aging memory for pictures: using high-density event-related potentials to understand the effect of aging on the picture superiority effect.

High-density event-related potentials (ERPs) were used to understand the effect of aging on the neural correlates of the picture superiority effect. Pictures and words were systematically varied at study and test while ERPs were recorded at retrieval. Here, the results of the word-word and picture-picture study-test conditions are presented.

Trovafloxacin-induced gene expression changes in liver-derived in vitro systems: comparison of primary human hepatocytes to HepG2 cells.

Primary human hepatocytes (PHH) are a main instrument in drug metabolism research and in the prediction of drug-induced phase I/II enzyme induction in humans. The HepG2 liver-derived cell line is commonly used as a surrogate for human hepatocytes, but its use in absorption, distribution, metabolism, and excretion and toxicity studies can be limited because of lowered basal levels of metabolizing enzymes. Despite the widespread use of HepG2 cells, a comparison of their transcriptomes with those of PHH has not been well characterized.

Memory for the September 11, 2001, terrorist attacks one year later in patients with Alzheimer's disease, patients with mild cognitive impairment, and healthy older adults.

Although there are many opportunities to study memory in patients with Alzheimer's disease (AD) in the laboratory, there are few opportunities to study memory for real world events in these patients. The September 11, 2001 terrorist attacks provided one such opportunity. Patients with AD, patients with mild cognitive impairment (MCI), and healthy older adults were given a telephone questionnaire in the initial weeks after the event, again three to four months later, and finally one year afterwards to evaluate their memory for the September 11, 2001 terrorist attacks.

G1P3, an IFN-induced survival factor, antagonizes TRAIL-induced apoptosis in human myeloma cells.

The effectiveness of IFN-alpha2b for human multiple myeloma has been variable. TRAIL has been proposed to mediate IFN-alpha2b apoptosis in myeloma. In this study we assessed the effects of IFN-alpha2b signaling on the apoptotic activity of TRAIL and human myeloma cell survival.

Gene expression profiling of rat liver reveals a mechanistic basis for ritonavir-induced hyperlipidemia.

The molecular mechanisms of action of a HIV protease inhibitor, ritonavir, on hepatic function were explored on a genomic scale using microarrays comprising genes expressed in the liver of Sprague-Dawley rats (Rattus norvegicus). Analyses of hepatic transcriptional fingerprints led to the identification of several key cellular pathways affected by ritonavir treatment. These effects were compared to a compendium of gene expression responses for 52 unrelated compounds and to other protease inhibitors, including atazanavir and two experimental compounds.

Preserved metamemorial ability in patients with mild Alzheimer's disease: shifting response bias.

Patients with mild Alzheimer's disease (AD) display a greater tendency to endorse unstudied items as "old" on memory tests than healthy older adults. This liberal response bias may result in mistaken beliefs about the completion of common tasks. This research attempted to determine whether it was possible to shift the response bias of mild AD patients to be more conservative on a recognition memory test through behavioral intervention.

Development of an approach for ab initio estimation of compound-induced liver injury based on global gene transcriptional profiles.

Toxicity is a major cause of failure in drug development. A toxicogenomic approach may provide a powerful tool for better assessing the potential toxicity of drug candidates. Several approaches have been reported for predicting hepatotoxicity based on reference compounds with well-studied toxicity mechanisms.

A culture of safety or coping? Ritualistic behaviours in the operating theatre.

Objectives: The creation of a 'safety culture' is a health services priority, yet there is little contemporary research examining the tacit, customary practices that relate to clinical risk. This paper investigates how the ritualistic behaviours of surgeons and anaesthetists serve to normalize risks within the operating theatre, thereby inhibiting organizational learning and enabling such risks to recur.

Methods: A two-year ethnographic study in the operating department of a large teaching hospital in the north of England, including observations of the organizational and clinical setting and interviews with 80 members of staff.

Adaptive regulation or governmentality: patient safety and the changing regulation of medicine.

This paper explores how current 'patient safety' reforms offer to change the regulation of medicine. Drawing on existing literature, it is argued that this policy agenda represents a new frontier in medical/managerial relations, introducing a disciplinary expertise within the health service that provides managers with the knowledge and legitimacy to survey and scrutinise medical performance, made real through procedures for incident reporting and root-cause analysis. The extent of regulatory change is investigated, drawing on an ethnographic case study of one hospital.

N-{3-[2-(4-alkoxyphenoxy)thiazol-5-yl]-1-methylprop-2-ynyl}carboxy derivatives as acetyl-coA carboxylase inhibitors--improvement of cardiovascular and neurological liabilities via structural modifications.

A preliminary safety evaluation of ACC2 inhibitor 1-(S) revealed serious neurological and cardiovascular liabilities of this chemotype. A systematic structure-toxicity relationship study identified the alkyne linker as the key motif responsible for these adverse effects. Toxicogenomic studies in rats showed that 1-(R) and 1-(S) induced gene expression patterns similar to that seen with several known cardiotoxic agents such as doxorubicin.

Hypomagnesemia with secondary hypocalcemia due to a missense mutation in the putative pore-forming region of TRPM6.

Hypomagnesemia with secondary hypocalcemia is an autosomal recessive disorder caused by mutations in the TRPM6 gene. Current experimental evidence suggests that TRPM6 may function in a specific association with TRPM7 by means of heterooligomeric channel complex formation. Here, we report the identification and functional characterization of a new hypomagnesemia with secondary hypocalcemia missense mutation in TRPM6.

Doctors' thinking about 'the system' as a threat to patient safety.

'Systems thinking' is an important feature of the emerging 'patient safety' agenda. As a key component of a 'safety culture', it encourages clinicians to look past individual error to recognize the latent factors that threaten safety. This article investigates whether current medical thinking is commensurate with the idea of 'systems thinking' together with its implications for policy.

Investigations toward enhanced understanding of hepatic idiosyncratic drug reactions.

Idiosyncratic drug reactions (IDRs) of a hepatic origin are a major health concern and a notoriously difficult challenge for the pharmaceutical industry. These types of adverse events are rare, with a typical occurrence of 1 in 100 to 1 in 100,000 patients. Typical adverse outcomes are most likely statistically impossible to predict in traditional preclinical safety studies or clinical trials.

Impact of elevated UV-B radiation on photosynthetic electron transport, primary productivity and carbon allocation in estuarine epipelic diatoms.

Epipelic diatoms are important components of microphytobenthic biofilms. Cultures of four diatom species (Amphora coffeaeformis, Cylindrotheca closterium, Navicula perminuta and Nitzschia epithemioides) and assemblages of mixed diatom species collected from an estuary were exposed to elevated levels of ultraviolet-B (UV-B) radiation. Short exposures to UV-B resulted in decreases in photosystem II (PSII) photochemistry, photosynthetic electron transport, photosynthetic carbon assimilation and changes in the pattern of allocation of assimilated carbon into soluble colloidal, extracellular polysaccharides (EPS) and glucan pools.

Trace metal bioaccumulation in eight common coastal Australian polychaeta.

Whole tissue trace metal concentrations of ten metals in eight common coastal Australian polychaete species collected from uncontaminated locations were measured. The mean concentration range for each trace metal was: Mn: 2.6-13 microg g(-1); Co: 0.

Modest inflammation enhances diclofenac hepatotoxicity in rats: role of neutrophils and bacterial translocation.

Idiosyncratic adverse drug reactions (IADRs) represent an important human health problem, yet animal models for preclinical prediction of these reactions are lacking. Recent evidence in animals suggests that some IADRs arise from drug interaction with an inflammatory episode that renders the liver sensitive to injury. Diclofenac (DCLF) is one of those drugs for which the clinical use is limited by idiosyncratic liver injury.

Safety and complexity: inter-departmental relationships as a threat to patient safety in the operating department.

Purpose: Current thinking about "patient safety" emphasises the causal relationship between the work environment and the delivery of clinical care. This research draws on the theory of normal accidents to extend this analysis and better understand the "organisational factors" that threaten safety.

Design/methodology/approach: Ethnographic research methods were used, with observations of the operating department setting for 18 month and interviews with 80 members of hospital staff.

Episodic memory in Alzheimer's disease: separating response bias from discrimination.

Most studies examining episodic memory in Alzheimer's disease (AD) have focused on patients' impaired ability to remember information, leading to poor discrimination between studied and unstudied items at test. Poor discrimination, however, can also be attributable to an abnormally high rate of false alarms. One cause of a high false alarm rate is an abnormally liberal response bias; that is, responding "old" too liberally to the test items.

Tuberculosis notifications in Australia, 2004.

The National Notifiable Disease Surveillance System received 1,076 tuberculosis (TB) notifications in 2004, of which 1,043 were new cases and 33 were relapses. The incidence of TB in Australia has remained at a stable rate since 1985 and was 5.4 cases per 100,000 population in 2004.

Imaging the production of singlet oxygen in vivo using a new fluorescent sensor, Singlet Oxygen Sensor Green.

Singlet oxygen is known to be produced by cells in response to photo-oxidative stresses and wounding. Due to singlet oxygen being highly reactive, it is thought to have a very short half-life in biological systems and, consequently, it is difficult to detect. A new commercially available reagent (singlet oxygen sensor green, SOSG), which is highly selective for singlet oxygen, was applied to a range of biological systems that are known to generate singlet oxygen.

Development of a toxicogenomics in vitro assay for the efficient characterization of compounds.

In vitro toxicogenomics represents a useful approach for evaluating the toxic properties of new drug candidates early in the drug discovery process using minimal amounts of compounds. The aim of this study was to develop in vitro-based gene expression assays for two prototypical toxicological classes: aryl hydrocarbon receptor (AhR) agonists and peroxisome proliferator activated receptor alpha (PPAR alpha) agonists. Primary rat hepatocytes were exposed to a number of class-specific compounds, including 3-methylcholanthrene, aroclor, and beta-napthoflavone as AhR agonists, bezafibrate, clofibrate, and Wy-14643 as peroxisome proliferators, and chlorpheniramine, penicillin and spectinomycin as negative controls.

Rules, safety and the narrativisation of identity: a hospital operating theatre case study.

Patient safety has become a health policy priority around the world. Acknowledging that 'to err is human' has led to attempts to design systems and rules that limit the capacity for individual discretion and thereby reduce clinical errors. In addition, great emphasis is being placed on the need to eradicate cultures of blame, which are assumed to discourage clinicians from reporting errors, and to establish a 'safety culture', which encourages openness and honesty.

Gene expression in human hepatocytes in suspension after isolation is similar to the liver of origin, is not affected by hepatocyte cold storage and cryopreservation, but is strongly changed after hepatocyte plating.

Isolated primary human hepatocytes are a well accepted system for evaluating pharmacological and toxicological effects in humans. However, questions remain regarding how culturing affects the liver-specific functions of the hepatocytes. In addition, cryopreservation could also potentially affect the differentiation state of the hepatocytes.