The poxvirus protein A52R targets Toll-like receptor signaling complexes to suppress host defense

Toll-like receptors (TLRs) are crucial in the innate immune response to pathogens, in that they recognize and respond to pathogen associated molecular patterns, which leads to activation of intracellular signaling pathways and altered gene expression. Vaccinia virus (VV), the poxvirus used to vaccinate against smallpox, encodes proteins that antagonize important components of host antiviral defense. Here we show that the VV protein A52R blocks the activation of the transcription factor nuclear factor kappa B (NF-kappa B) by multiple TLRs, including TLR3, a recently identified receptor for viral RNA. A52R associates with both interleukin 1 receptor-associated kinase 2 (IRAK2) and tumor necrosis factor receptor-associated factor 6 (TRAF6), two key proteins important in TLR signal transduction. Further, A52R could disrupt signaling complexes containing these proteins. A virus deletion mutant lacking the A52R gene was attenuated compared with wild-type and revertant controls in a murine intranasal model of infection. This study reveals a novel mechanism used by VV to suppress the host immunity. We demonstrate viral disabling of TLRs, providing further evidence for an important role for this family of receptors in the antiviral response.

Morphological consequences of lateral outfracture of the inferior turbinate

Objective: We report three cases of lateral outfracture of the inferior turbinate, which demonstrate a range of changes in the size, position and shape of the inferior turbinate.

Method: During a study of the validity of computer modelling of nasal airflow, computed tomography scans of the noses of patients who had undergone lateral outfracture of the inferior turbinate were collected. The pre-operative scan was compared with the post-operative scan six weeks later.

Results: In one patient, there was only a small lateral displacement of the inferior turbinate. In the other two cases, appreciable reduction in the volume of one inferior turbinate was noted, in addition to minor changes in the shape.

Conclusion: Lateral outfracture of the inferior turbinate produces varied and inconsistent changes in morphology which may affect the shape, size and position of the turbinate.

The Engine of Thought Is a Hybrid: Roles of Associative and Structured Knowledge in Reasoning

Across a range of domains in psychology different theories assume different mental representations of knowledge. For example, in the literature on category-based inductive reasoning, certain theories (e.g., Rogers & McClelland, 2004; Sloutsky & Fisher, 2008) assume that the knowledge upon which inductive inferences are based is associative, whereas others (e.g., Heit & Rubinstein, 1994; Kemp & Tenenbaum, 2009; Osherson, Smith, Wilkie, López, & Shafir, 1990) assume that knowledge is structured. In this article we investigate whether associative and structured knowledge underlie inductive reasoning to different degrees under different processing conditions. We develop a measure of knowledge about the degree of association between categories and show that it dissociates from measures of structured knowledge. In Experiment 1 participants rated the strength of inductive arguments whose categories were either taxonomically or causally related. A measure of associative strength predicted reasoning when people had to respond fast, whereas causal and taxonomic knowledge explained inference strength when people responded slowly. In Experiment 2, we also manipulated whether the causal link between the categories was predictive or diagnostic. Participants preferred predictive to diagnostic arguments except when they responded under cognitive load. In Experiment 3, using an open-ended induction paradigm, people generated and evaluated their own conclusion categories. Inductive strength was predicted by associative strength under heavy cognitive load, whereas an index of structured knowledge was more predictive of inductive strength under minimal cognitive load. Together these results suggest that associative and structured models of reasoning apply best under different processing conditions and that the application of structured knowledge in reasoning is often effortful.

Supported decision making: a review of the international literature

Supported decision making (SDM) refers to the process of supporting people, whose decision making ability may be impaired, to make decisions and so promote autonomy and prevent the need for substitute decision making. There have been developments in SDM but mainly in the areas of intellectual disabilities and end-of-life care rather than in mental health. The main aim of this review was to provide an overview of the available evidence relevant to SDM and so facilitate discussion of how this aspect of law, policy and practice may be further developed in mental health services. The method used for this review was a Rapid Evidence Assessment which involved: developing appropriate search strategies; searching relevant databases and grey literature; then assessing, including and reviewing relevant studies. Included studies were grouped into four main themes: studies reporting stakeholders’ views on SDM; studies identifying barriers to the implementation of SDM; studies highlighting ways to improve implementation; and studies on the impact of SDM. The available evidence on implementation and impact, identified by this review, is limited but there are important rights-based, effectiveness and pragmatic arguments for further developing and researching SDM for people with mental health problems.

Optimised extraction of heterocyclic aromatic amines from blood using hollow fibre membrane liquid-phase microextraction and triple quadrupole mass spectrometry

Heterocyclic aromatic amines (HCA) are carcinogenic mutagens formed during cooking of proteinaceous foods, particularly meat. To assist in the ongoing search for biomarkers of HCA exposure in blood, a method is described for the extraction from human plasma of the most abundant HCAs: 2-Amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) (and its isomer 7,8-DiMeIQx), using Hollow Fibre Membrane Liquid-Phase Microextraction. This technique employs 2.5 cm lengths of porous polypropylene fibres impregnated with organic solvent to facilitate simultaneous extraction from an alkaline aqueous sample into a low volume acidic acceptor phase. This low cost protocol is extensively optimised for fibre length, extraction time, sample pH and volume. Detection is by UPLC-MS/MS using positive mode electrospray ionisation with a 3.4 min runtime, with optimum peak shape, sensitivity and baseline separation being achieved at pH 9.5. To our knowledge this is the first description of HCA chromatography under alkaline conditions. Application of fixed ion ratio tolerances for confirmation of analyte identity is discussed. Assay precision is between 4.5 and 8.8% while lower limits of detection between 2 and 5 pg/mL are below the concentrations postulated for acid-labile HCA-protein adducts in blood.

Developing a Reporting Guideline for Social and Psychological Intervention Trials

Social and psychological interventions are often complex. Understanding randomized controlled trials (RCTs) of these complex interventions requires a detailed description of the interventions tested and the methods used to evaluate them; however, RCT reports often omit, or inadequately report, this information. Incomplete and inaccurate reporting hinders the optimal use of research, wastes resources, and fails to meet ethical obligations to research participants and consumers. In this article, we explain how reporting guidelines have improved the quality of reports in medicine and describe the ongoing development of a new reporting guideline for RCTs: Consolidated Standards of Reporting Trials-SPI (an extension for social and psychological interventions). We invite readers to participate in the project by visiting our website, in order to help us reach the best-informed consensus on these guidelines (http://tinyurl.com/CONSORT-study).

Working with fathers to improve children's well-being: Results of a survey exploring service provision and intervention approach in the UK

Interventions for fathers are a recent growth area in family services. Although some specific approaches are beginning to be evaluated, there is little known about what kinds of interventions are more generally being used in practice. A web-based survey of practitioners was conducted in the UK, with contact being made via local authority service managers. Two hundred and twenty-one responses were received from 53% of local authorities. Both interventions specifically for fathers and services for both parents were targeted in the survey. Results are reported on organisational location; targeting of services; type of intervention; numbers and percentages of men attending services, recruitment of fathers; evaluation strategies; and ideological and theoretical approaches. Numbers of fathers engaged are relatively low - e.g. the median annual number of fathers attending structured parenting courses was eight and in courses for both parents, 21% of those attending were men. Responses on ideological and theoretical approaches suggest that overt gender politics play only a small part, but that the dominant views of practitioners are in line with mainstream approaches to parenting support. Cognitive and behavioral approaches were the most popular.