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Piperidine ether and aryl piperazine hydantoins are reported as potent inhibitors of MMP13. A medicinal chemistry campaign focused on replacing the reverse hydroxamate zinc binding group associated with historical inhibitors with a hydantoin zinc binding group then optimising MMP13 potency, solubility and DMPK properties whilst maintaining good selectivity over MMP14. A number of high quality candidates were progressed and following rat and dog safety evaluation, AZD6605 (3m) was identified as a candidate drug., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Generalist health care professionals are increasingly challenged to provide mental health care within their own clinical specialties. Educators are challenged with providing innovative, engaging and accessible education programs to increase the mental health knowledge and skills of generalist health care professionals. Simulation is increasingly being used within learning curricula to optimise learning and the use of information and communication technology has emerged as a novel way of providing simulated learning. This paper describes the development process of an interactive, multimedia 'eSimulation' mental health education program for generalist health care professionals. The resulting eSimulation education program incorporated the following five key attributes of simulation: (1) Creating a hypothetical opportunity; (2) Authentic representation; (3) Active participation; (4) Integration; and (5) Repetition, evaluation and reflection. This process can be used to guide nursing educators in the development of tailored eSimulation education programs. An evaluation of the eSimulation will be reported elsewhere, in Part 2 of this paper.

Objective: The objective of this paper was to evaluate breakaway technique training with neuroscience nursing staff as a measure of increased confidence and safety in managing aggression., Methods: A quasi experimental design was used in a sample of neuroscience nursing staff (n=31), participating in 2×1h breakaway technique workshops. The workshops consisted of supervised skills training in safe breakaway techniques. A pre- and postintervention-matched questionnaire measuring confidence and safety around managing aggressive patients, and exposure to and confidence in dealing with breakaways, was self administered., Results: Statistically significant increases in confidence and safety in working with aggressive patients, and confidence levels for safe breakaways were reported. Qualitative comments demonstrated a desire for ongoing skills workshops., Conclusions: This study provides early evidence of the importance of incorporating breakaway training into existing training programs which aim to minimise and manage aggression and violence in generalist settings.

Clinical supervision (CS) has been identified within nursing as a process for improving clinical practice and reducing the emotional burden of nursing practice. Little is known about its implementation across large tertiary referral hospitals. The purpose of this study is to evaluate the implementation of clinical supervision across several different nursing specialities at a teaching hospital in Sydney, Australia. Using a model of nursing implementation science, a process was developed at the study site that facilitated the development, implementation and evaluation of the project. After a 6-month study period, the CS groups were postevaluated using a survey tool developed for the project. A total of nine CS groups were in operation over the 6-month study period. A predominant focus within the sessions was one of the collegial support and developing standards of practice. The process was able to achieve wide hospital-based support for the role of CS from the senior nurse executives to junior nurses. Whilst there was overall positive support for the CS groups, logistical and resource challenges remain, in the effective roll out of CS to large numbers of nurses., (© 2011 The Authors. Scandinavian Journal of Caring Sciences © 2011 Nordic College of Caring Science.)

Background: To investigate the incidence, characteristics, and predisposing factors for cerebral white matter lesions in patients with Crohn's disease., Methods: We retrospectively evaluated the incidence and characteristics of cerebral T2 white matter abnormalities in 54 patients with Crohn's disease and compared to 100 age-matched controls. We also investigated potential co-morbidities known to be associated with white matter abnormalities in Crohn's patients with normal and abnormal Magnetic Resonance Imaging (MRI)., Results: Seventy-two percent of patients with Crohn's disease had T2 white matter abnormalities, as compared with 34% of the age-matched controls (P < .001). Lesion severity and size were not significantly different between the two groups; however, periventricular distribution and fulfillment of the Barkhof MRI criteria were overrepresented in Crohn's population. History of hypertension, diabetes, and migraine; gender, duration of disease and prior exposure to anti-tumor necrosis factor were not significantly different between Crohn's patients with and without white matter abnormalities; however, patients with lesions were significantly older than those without., Conclusions: Patients with Crohn's disease have a higher incidence of white matter T2 hyperintensities as compared with controls. Age was the only significant factor for the abnormalities within Crohn's group. White matter T2 hyperintensities are likely another extra-intestinal manifestation of Crohn's disease., (Copyright © 2010 by the American Society of Neuroimaging.)

A new achiral class of N-hydroxyformamide inhibitor of both ADAM-TS4 and ADAM-TS5, 2 has been discovered through modification of the complex P1 group present in historical inhibitors 1. This structural change improved the DMPK properties and greatly simplified the synthesis whilst maintaining excellent cross-MMP selectivity profiles. Investigation of structure-activity and structure-property relationships in the P1 group resulted in both ADAM-TS4 selective and mixed ADAM-TS4/5 inhibitors. This led to the identification of a pre-clinical candidate with excellent bioavailability across three species and predicting once daily dosing kinetics., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

There has been much recent literature on the technical parameters of electroconvulsive therapy (ECT) with regard to improving efficacy and minimizing adverse effects, but relatively little on ECT service delivery. This paper will discuss the development and characteristics of an ECT service at a teaching hospital in metropolitan Sydney, New South Wales, Australia. A mixture of qualitative and quantitative methods, including a selective literature review and audit of ECT use were used. The results of the audit were compared with the 2007 revision of the Royal Australian and New Zealand College of Psychiatrists' clinical memorandum on ECT. We discuss issues, such as the optimal site for ECT delivery, ECT mental health nurse coordinator role, credentialing of psychiatrists, registrar supervision, and the development of an ECT committee. A significant finding of the audit was that the majority of patients were treated under the New South Wales Mental Health Act, and voluntary patients were more likely to have a diagnosis of a depressive disorder, whereas involuntary patients were more likely to have a non-mood disorder diagnosis. This study has shown that auditing of ECT practices and services by mental health nurses is essential for quality improvement processes. The audit highlighted areas of service delivery that should be subject to review and evaluation against professional standards., (© 2011 The Authors. International Journal of Mental Health Nursing © 2011 Australian College of Mental Health Nurses Inc.)

Vaccines, antibiotics, and other therapeutic agents used to combat disease in poultry generate recurring costs and the potential of residues in poultry products. Enhancing the immune response using alternative approaches such as selection for increased disease resistance or dietary immunomodulation may be effective additions to the portfolio of strategies the industry applies in poultry health management. The objective of this study was to characterize the effects of dietary supplementation with 3 immunomodulators [ascorbic acid, 1,3-1,6 β-glucans from baker's yeast, and corticosterone] on cytokine gene expression in the spleen of 3 distinct genetic lines of chickens. Relative mRNA expression levels were determined using quantitative reverse transcriptase PCR for IL-1β, IL-2, inducible nitric oxide synthase, and toll-like receptors 4 and 15, all of which play important roles in chicken immune function. Expression data were analyzed by mixed model analysis. The only significant effect detected was sex effect (P < 0.04) on expression of IL-1β. The present findings suggest the need for further investigations into the effects of dietary immunomodulators on cytokine gene expression in chickens so as to generate a better understanding of the immunomodulation process.

Recent advances in high-throughput technology facilitate massive data collection and sharing, enabling neuroscientists to explore the brain across a large range of spatial scales. One such form of high-throughput data collection is the construction of large-scale mosaic volumes using light microscopy (Chow et al., 2006; Price et al., 2006). With this technology, researchers can collect and analyze high-resolution digitized volumes of whole brain sections down to 0.2 μm. However, until recently, scientists lacked the tools to easily handle these large high-resolution datasets. Furthermore, artifacts resulting from specimen preparation limited volume reconstruction using this technique to only a single tissue section. In this paper, we carefully describe the steps we used to digitally reconstruct a series of consecutive mouse brain sections labeled with three stains, a stain for blood vessels (DiI), a nuclear stain (TO-PRO-3), and a myelin stain (FluoroMyelin). These stains label important neuroanatomical landmarks that are used for stacking the serial sections during reconstruction. In addition, we show that the use of two software applications, ir-Tweak and Mogrifier, in conjunction with a volume flattening procedure enable scientists to adeptly work with digitized volumes despite tears and thickness variations within tissue sections. These applications make processing large-scale brain mosaics more efficient. When used in combination with new database resources, these brain maps should allow researchers to extend the lifetime of their specimens indefinitely by preserving them in digital form, making them available for future analyses as our knowledge in the field of neuroscience continues to expand.

Two series of N-hydroxyformamide inhibitors of ADAM-TS4 were identified from screening compounds previously synthesised as inhibitors of matrix metalloproteinase-13 (collagenase-3). Understanding of the binding mode of this class of compound using ADAM-TS1 as a structural surrogate has led to the discovery of potent and very selective inhibitors with favourable DMPK properties. Synthesis, structure-activity relationships, and strategies to improve selectivity and lower in vivo metabolic clearance are described., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Host defense peptides (HDPs) constitute a large group of natural broad-spectrum antimicrobials and an important first line of immunity in virtually all forms of life. Specific augmentation of synthesis of endogenous HDPs may represent a promising antibiotic-alternative approach to disease control. In this study, we tested the hypothesis that exogenous administration of butyrate, a major type of short-chain fatty acids derived from bacterial fermentation of undigested dietary fiber, is capable of inducing HDPs and enhancing disease resistance in chickens. We have found that butyrate is a potent inducer of several, but not all, chicken HDPs in HD11 macrophages as well as in primary monocytes, bone marrow cells, and jejuna and cecal explants. In addition, butyrate treatment enhanced the antibacterial activity of chicken monocytes against Salmonella enteritidis, with a minimum impact on inflammatory cytokine production, phagocytosis, and oxidative burst capacities of the cells. Furthermore, feed supplementation with 0.1% butyrate led to a significant increase in HDP gene expression in the intestinal tract of chickens. More importantly, such a feeding strategy resulted in a nearly 10-fold reduction in the bacterial titer in the cecum following experimental infections with S. enteritidis. Collectively, the results indicated that butyrate-induced synthesis of endogenous HDPs is a phylogenetically conserved mechanism of innate host defense shared by mammals and aves, and that dietary supplementation of butyrate has potential for further development as a convenient antibiotic-alternative strategy to enhance host innate immunity and disease resistance.

Purpose: This paper explores the use of capacity building practice as an approach for the mental health liaison nurse (MHLN)., Conclusions: The role of the MHLN has established itself within nursing, with various approaches to the role documented in the nursing literature. Most descriptions of the role are limited by simply explaining what the MHLN does, rather than explaining the underlying approach and evaluation of the model suggested. Capacity building practice is explored in the context of the liaison role, and its use is demonstrated in a clinical example of suicide risk in a general hospital setting., Practical Implications: The future scope of MHLN and their use of capacity building approaches may lead to the improvement of consumer health outcomes and also develop the skill of the non-mental health nurse in generalist settings., (© 2010 Wiley Periodicals, Inc.)

Nurses in most clinical settings experience difficult 'nurse patient relationships' at various times. Attempts to describe and articulate how to manage such difficult relationships can be found, but often lay blame at the patient level and ultimately leave the nurse less confident to improve patient care. This study uses an action research approach in working with nurses in a generalist setting in developing an educational strategy that helped to improve their knowledge, skills and confidence in working within the 'difficult nurse patient relationship' paradigm. Through the experiential style learning methodology of scenario based learning and applying this via e-learning, an effective educational approach has been developed. Using a quasi-experimental design to evaluate the e-learning package, significant increases in knowledge, skill, confidence and reduced nurse stress as measured on the 'difficult patient stress scale' were shown. This approach allows nurses to reflect on their own behaviour and improve their ability to enhance patient care in difficult to manage nursing care situations.

Personality disorder is argued to be the most prevalent psychiatric disorder and is considered to be a significant public health burden, yet there is little evidence that the disorder occupies a commensurate place in public health service planning, appropriate to such a burden. This paper reviews the prevalence and treatment outcome studies of individuals with personality disorder. The literature search highlighted prevalence studies and evidence based pharmacological, psychosocial, and alliance based interventions within this area. From this review, the place of mental health nurses within health service models is discussed.

This case study reviews 11 sessions of art psychotherapy with a consumer diagnosed with having borderline personality disorder. A consumer who reported difficulty in communicating her lived trauma verbally and engaged in self-harming behaviour was offered individual art therapy sessions following a consultation between an art therapy student and clinical nurse consultant in an attempt to understand her experiences and to collaboratively engage her. Notes were taken after each session by the art therapy student, reflecting conversations with this consumer while they were engaged in art making, which were subsequently explored within formal clinical supervision sessions with a mental health nurse consultant. An art portfolio is reproduced. It illustrates the expressive power of image creation. The key features of the images were that of lived trauma, the externalization of thoughts and feelings, and intense emotional expression. The results of this chronological art portfolio case study indicated therapeutic benefits from the intervention for this consumer. Further investigations of this type of intervention are warranted within the mental health setting.

For more than 20 years, countries and their agencies which monitor radionuclide discharge sites and storage facilities have relied on the National Institute of Standards and Technology (NIST) Standard Reference Material (SRM) 4355 Peruvian Soil. Its low fallout contamination makes it an ideal soil blank for measurements associated with terrestrial-pathway-to-man studies. Presently, SRM 4355 is out of stock, and a new batch of the Peruvian soil is currently under development as future NIST SRM 4355A. Both environmental radioanalytical laboratories and mass spectrometry communities will benefit from the use of this SRM. The former must assess their laboratory procedural contamination and measurement detection limits by measurement of blank sample material. The Peruvian Soil is so low in anthropogenic radionuclide content that it is a suitable virtual blank. On the other hand, mass spectrometric laboratories have high sensitivity instruments that are capable of quantitative isotopic measurements at low plutonium levels in the SRM 4355 (first Peruvian Soil SRM) that provided the mass spectrometric community with the calibration, quality control, and testing material needed for methods development and legal defensibility. The quantification of the ultra-low plutonium content in the SRM 4355A was a considerable challenge for the mass spectrometric laboratories. Careful blank control and correction, isobaric interferences, instrument stability, peak assessment, and detection assessment were necessary. Furthermore, a systematic statistical evaluation of the measurement results and considerable discussions with the mass spectroscopy metrologists were needed to derive the certified values and uncertainties. The one sided upper limit of the 95% tolerance with 95% confidence for the massic (239)Pu content in SRM 4355A is estimated to be 54,000 atoms/g.

Consumer satisfaction is today, widely accepted as a measure of the level and quality of service received by consumers. The aim of this survey-based study is to explore consumer satisfaction with quality of care, staff, environment and discharge in a south eastern Sydney adult acute inpatient mental health unit. A cross-sectional analysis is pursued in order to identify aspects of the patient stay, which form an associative relationship with an overall rating of consumer satisfaction on a 10-point scale. During the survey period, there were 182 discharges. Seventy questionnaires (38.5%) were returned from this group. The survey results highlight a number of areas of identified need, enabling the service to prioritize organizational systems around meeting these needs. Multiple regression analysis identified three items in the survey, which were independently significant associates of overall consumer satisfaction. They included being happy with the service provided by the consumer support worker, having support for services on discharge and feeling safe and secure on the ward. The model containing these three items accounted for 50% of the variation in overall satisfaction. Two primary interventions have been developed because survey administration which, it is hoped, will address issues raised in the survey. The interventions were the development of an admission and discharge pathway and a ward-based psychosocial intervention programme, which includes the involvement of consumer support workers.

Objective: We aimed to determine the effectiveness of a hand-held record (the 'Blue Card') for seriously mentally ill consumers by investigating effects on consumer knowledge of physical health risk factors, consumer involvement in care and communication with healthcare professionals., Method: Consumers were given and educated in the use of the Blue Card, which contained information regarding their physical health. Consumers completed a pre- and post-knowledge questionnaire and commented on the effectiveness of the Blue Card with respect to their knowledge of physical health risks., Results: Statistically significant improvements in consumer knowledge were shown at the 3-month follow-up, with high retention of the Blue Card being demonstrated. Consumers that used the card described their use of the card positively., Conclusions: The results are very encouraging. Further studies of this low-cost intervention are warranted to establish its effectiveness and utility.

Understanding the changes in host gene expression that occur with bacterial infection will help to elucidate the basis of molecular genetic control of disease resistance. The effect of infecting chicks with Salmonella enterica serovar Enteritidis on the RNA expression level of Toll-like receptor (TLR) genes, and the correlation between TLR RNA expression level and bacterial burden in the cecum and spleen of young birds was studied. Chicks from two advanced intercross lines were either infected or mock infected with S. enteritidis at 1 day of age. The RNA expression levels of TLR2, TLR4 and TLR5 genes were assessed by quantitative reverse transcriptase-PCR (qRT-PCR) in cecum and spleen tissues harvested at one week post-infection. Infected chicks had significant upregulation of TLR2 RNA expression in spleen, TLR4 RNA expression in both cecum and spleen, and downregulation of TLR5 RNA expression in cecum. Bacterial burden of S. enteritidis in infected birds was not correlated with TLR RNA expression level. Infecting chicks with S. enteritidis caused an increase in TLR2, TLR4 and TLR5 RNA expression level in spleen in males but not in females. The effect of sex on response to S. enteritidis infection suggests a role for TLR signaling pathways in sex-based modulation of immune response to pathogens. High correlation between TLR2 and TLR4 mRNA expression level in cecum of S. enteritidis infected birds suggests coordinated regulation or simultaneous stimulation of these genes by S. enteritidis. In conclusion, this study clearly showed that young chicks respond to S. enteritidis infection by upregulating TLR2, TLR4 RNA expression. The downregulation of TLR5 RNA expression was observed in cecum by S. enteritidis infection, which might be beneficial to protect host cells from overstimulation by bacterial flagellin.

A workshop was held from 28 February to 2 March 2006 at the National Institute of Standards and Technology (NIST) to evaluate the needs for new directions for complex matrix reference materials certified for radionuclide content, interlaboratory comparisons and performance evaluation (PE) programs. The workshop identified new radioanalytical metrology thrust areas needed for environmental, radiobioassay, emergency consequence management, and nuclear forensics, attribution, nonproliferation, and safeguards.

Aim: To audit current practice regarding selection and use of graduated elastic compression stockings (GECS) in the authors' Trust. Following a literature review it was important for the Trust that the authors audited current practice before the development and implementation of any new guidelines., Background: A literature review enabled the authors to establish best practice principles for the use of GECS and develop guidelines for use across their Trust. However, feedback from various sources highlighted conflicting practices regarding the methods by which patients either did or did not receive stockings, and which lengths and brands were used. As the guidelines aimed to allow implementation of standardized change across the Trust, it was important to establish current practice with regard to GECS selection and use. Therefore, an audit tool was developed carried out on the use of GECS., Methods: An audit tool was developed and implemented to establish the practices before the implementation of the guidelines., Results: The audit demonstrated that there was no consistent policy within the surgical services directorate for the correct use of GECS., Conclusions: It is important that all healthcare providers have a local policy for GECS use, which makes it clear how an assessment for patients requiring GECS needs to be conducted and how that assessment is documented.

Two M5.1 and M15.2 B complex congenic lines of Fayoumi chickens were evaluated for body weight loss and faecal oocyst counts as parameters of avian coccidiosis. M5.1 chickens exhibited resistance to E. maxima compared with M15.2. To correlate the differential responses of the M5.1 and M15.2 lines to E. maxima infection with cellular immune responses, the expression levels of mRNAs encoding 14 immune-related molecules were measured by quantitative RT-PCR in intestinal intraepithelial lymphocytes (IELs) and splenocytes at 0, 3, 4, and 5 days following parasite infection. Intestinal IELs from M5.1 chickens expressed higher levels of transcripts encoding interferon gamma (IFNG), interleukin-lbeta (1L1B), IL6, IL8, IL12, IL15, IL17A, inducible nitric oxide synthase (iNOS), and lipopolysaccharide-induced tumour necrosis a factor (LITAF), and lower levels of mRNAs for IFNA, IL10, IL17D, NK-lysin (NKL), and tumour necrosis factor superfamily 15 (TNFSF15) at 3 days post infection, compared with the M15.2 line. In the spleen, E. maxima infection was associated with higher expression levels of IFNA, and IL15 and lower levels of IL6, IL17D, and IL12 in M5.1 compared to M15.2 birds. Using an intestinal IEL cDNA microarray, the differential dynamics of gene expression in the gut of M5.1 and M15.2 chickens following experimental coccidiosis were evident. In particular, the genes encoding lymphotactin and parathymosin were expressed at significantly higher levels in M5.1 compared with M15.2 line chickens. In conclusion, genetic determinants within the chicken major histocompatibility complex (MHC) B complex influence resistance to E. maxima infection by controlling the local and systemic expression of immune-related cytokine and chemokine genes.

Infectious bursal disease virus (IBDV) causes highly contagious, immunosuppressive disease that leads to high mortality in young chickens. The purpose of this study was to look for the genetic regulation of the immune acute immune response to IBDV in our selected lines. Chicks of a F2 generation of two lines divergently selected for early high (HH) or low (LL) antibody (Ab) response to Escherichia coLi vaccination were challenged with virulent IBDV. Viral load in infected bursae was used to determine resistant (R) and susceptible (S) birds. By using a 13K chicken cDNA microarray, and pooled spleen mRNA of R, S and non-challenged, control (C) chicks, several genes were identified with differential expression associated with host resistance to IBDV. These genes were also subjected to RT-PCR on individual samples to verify the results obtained from microarrays. The major finding was the co-upregulation of seven genes--ETS2, H963, RGS1, ABIN-2, CREM/ICER, DUSP1 and CXCR4- in several R, but not S or C individuals, and characterized by a high correlation of expression levels. Resistance also generally coincided with reduced transcript levels of acute-phase serum amyloid A (A-SAA) and increased levels of IL-8. Based on reported functions of these genes, these findings suggest that resistance was mediated by the activation of specific cellular mechanisms, indicated by increased activity of splenic macrophages and T-lymphocytes 3 days post-challenge.

Availability of a dense single-nucleotide polymorphism (SNP) map in chickens has allowed for whole-genome QTL mapping for disease resistance. In this study, two F8 advanced intercross lines of broiler by Fayoumi and broiler by Leghorn chickens, and a dense, genome-wide SNP panel were used to map genomic regions associated with host resistance to bacterial colonisation. One week after inoculation of day-old chicks with Salmonella enteritidis (SE), caecum and spleen tissues were collected to quantitate the bacterial load. Of 2733 genotyped SNPs, 875 were homozygous and the remaining SNPs with a minor allele frequency of > 0.2 were individually tested for association with SE burden by utilising a Chi-square log-likelihood test between models with and without SNP genotype. Using a Q-value of 25%, calculated utilising 1207 SNPs with Chi-square P-Value < 1.0 to control for false discovery, 21 SNPs identifying 19 genes were significantly associated with SE bacterial levels. Ten genes were in pathways associated with immune response to Salmonella (toll-like receptor signaling, apoptosis, and MAPK signaling), further supporting their involvement in host resistance pathways. In addition to identifying new candidate genes for bacterial resistance, the trait-associated SNPs may be useful in marker assisted selection programmes for disease resistance.

While rearing birds in confinement and at high density are very successful practices for producing poultry meat and eggs, these conditions may promote the spread of infectious diseases. Consequently, the poultry industry places greatemphasis on disease control measures, primarily at the animal husbandry level. The field of genomics offers great promise to complement these current control measures by providing information on the molecular basis for disease, disease resistance, and vaccinal immunity. This briefly summarizes some of our efforts to apply several genomic and functional genomics approaches to identify genes and pathways that confer genetic resistance to Marek's disease (MD), a herpesvirus-induced T cell lymphoma of chickens. By utilizing the "top-down" approach of QTL to identify genomics regions, and integrating it with "bottom-up" approaches of transcript profiling and Marek's disease virus (MDV)-chicken protein-protein interactions, three genes that confer resistance to MD are revealed, plus a number of other positional candidate genes of high confidence. These genes can be further evaluated in poultry breeding programmes to determine if they confer genetic resistance to MD. This integrative genomics strategy can be applied to other infectious diseases. The impact of the genome sequence and other technological advancements are also discussed.

Aim: To determine, through literature review, the current best practice for selecting and using graduated elastic compression stockings (GECS). In particular, literature was sought to clarify which patients should be given GECS, and whether there were any underlying research recommendations as to which length of stocking should be worn., Background: A procurement exercise identified that the clinical areas within the Surgical Services Directorate at each of the three hospital sites were spending significantly different amounts of money on the purchase of GECS and purchasing significantly different numbers per ward. Further analysis revealed that different hospital sites had different preferences for either knee-length or thigh-length stockings. Nurses and medical staff gave conflicting ideas for the correct use and type of stockings, which prompted the authors to access the literature to establish best guidelines., Methods: A literature review was used to develop best practice guidelines for the use of GECS., Results: There is good evidence from the literature demonstrating that the use of GECS in patients undergoing surgery can be effective in the prevention of deep vein thrombosis, used in conjunction with drug therapy, other prophylactic methods, or alone., Conclusions: There is strong evidence for the use of knee-length stockings instead of thigh-length stockings. It is critically important that patients are thoroughly assessed prior to the application of GECS.

Genome-wide association studies have become possible in the chicken because of the recent availability of the complete genome sequence, a polymorphism map and high-density single nucleotide polymorphism (SNP) genotyping platforms. We used these tools to study the genetic basis of a very high level of heterosis that was previously observed for fatness in two F(2) populations established by crossing one outbred broiler (meat-type) sire with dams from two unrelated, highly inbred, light-bodied lines (Fayoumi and Leghorn). In each F(2) population, selective genotyping was carried out using phenotypically extreme males for abdominal fat percentage (AF) and about 3000 SNPs. Single-point association analysis of about 500 informative SNPs per cross showed significant association (P < 0.01) of 15 and 24 markers with AF in the Broiler x Fayoumi and Broiler x Leghorn crosses respectively. These SNPs were on 10 chromosomes (GGA1, 2, 3, 4, 7, 8, 10, 12, 15 and 27). Interestingly, of the 39 SNPs that were significantly associated with AF, there were about twice as many homozygous genotypes associated with higher AF that traced back to the inbred lines alleles, although the broiler line had on average higher AF. These SNPs are considered to be associated with QTL with cryptic alleles. This study reveals cryptic alleles as an important factor in heterosis for fatness observed in two chicken F(2) populations, and suggests epistasis as the common underlying mechanism for heterosis and cryptic allele expression. The results of this study also demonstrate the power of high marker-density SNP association studies in discovering QTL that were not detected by previous microsatellite-based genotyping studies.

A 63-year-old female with known empty sella syndrome underwent coronary artery bypass grafting surgery. She became hypotensive immediately postoperatively and this did not respond to fluid resuscitation and inotropic therapy. Surgical re-exploration was undertaken and did not reveal any surgical cause. Pulmonary artery catheterisation confirmed a profound vasodilatory component to her shock. We believe this was due to unmasking of posterior pituitary hypofunction, in particular vasopressin insufficiency, due to metabolic stress. This rapidly corrected with an exogenous vasopressin infusion.

The neural networks in the crustacean stomatogastric ganglion are modulated by neuroactive substances released locally into the neuropil of the stomatogastric ganglion and by circulating hormones released by neuroendocrine structures including the pericardial organs. Using nanoscale liquid chromatography coupled to electrospray ionization quadrupole-time-of-flight mass spectrometry, we have identified and sequenced a novel B type allatostatin (CbAST-B1), VPNDWAHFRGSWamide, present in the pericardial organs of the crabs, Cancer borealis, and Cancer productus. We describe the physiological actions of CbAST-B1 on the pyloric rhythm of the stomatogastric ganglion of the crab, Cancer borealis. CbAST-B1 reduces the pyloric network frequency in a dose-dependent manner. The effect of bath-applied CbAST-B1 depends on the preceding physiological state of the preparation. Surprisingly, despite marked amino-acid sequence dissimilarity between the novel CbAST-B1 and the A type allatostatin family of peptides (AST-A), the physiological effects of CbAST-B1 are similar to those of AST-A.

Cytokines are secreted proteins involved with cell recruitment and regulation of both innate and adaptive immune responses. They are essential for an effective host immune response to pathogens. The objective of this study was to determine the effect of Salmonella enterica serovar Enteritidis (S. Enteritidis) exposure and genetic line on cytokine mRNA expression level of cultured chicken peripheral blood mononuclear cells (PBMC). Interleukin-2, interleukin-6 (IL-6), CXCLi2, and transforming growth factor-beta4 (TGF-B4) messenger ribonucleic acid expression was measured by quantitative reverse transcription-PCR assays in PBMC from 3 chicken lines (broiler, Leghorn, Fayoumi) after in vitro exposure to S. Enteritidis. The PBMC were isolated from uninfected birds and cultured overnight. The next day, live pathogenic S. Enteritidis was added to half of the cultures. All cultures were harvested after 2 or 4 h of exposure. Exposure to S. Enteritidis downregulated IL-6, CXCLi2, and TGF-beta4 but not interleukin-2 mRNA expression. No significant genetic line or exposure time effects were detected. These findings demonstrate that exposure of chicken PBMC to S. Enteritidis can induce a rapid change in both proinflammatory (IL-6, CXCLi2) and antiinflammatory (TGF-beta4) cytokine gene expression.

Millions of single nucleotide polymorphisms (SNP) are now known in the chicken, but the ones that segregate may differ among populations. The current study characterized a simple method to simultaneously identify SNP in populations and to estimate allele frequencies by using relative peak heights of nucleotides in sequencing traces from DNA pools. In the first experiment, known concentration gradients of alleles were produced by measured admixture of DNA from highly inbred individual chickens. In the second experiment, pools of DNA from 100 individuals of each of 3 populations were produced, and the estimated frequencies were compared with those from genotyping of individuals sampled from the same populations. Linear relationships (slope = 0.93 to 1.02) were demonstrated between relative peak heights of nucleotide sequence traces and allelic frequency from both types of experimental samples. The correlation of frequency estimates from pools and individual genotyping was 0.917 to 0.997. Therefore, relative peak heights of nucleotides in sequence traces from DNA isolated from blood pools provide accurate estimates of SNP frequencies of the population from which the pool individuals were sampled and can, therefore, increase efficiency of selecting SNP to genotype in specific populations.

This is a tale of when radio-opaque strips in surgical swabs aren't always radio-opaque. Sue Lamont has a 30-year background as a theatre nurse and a theatre manager. Her current role is clinical procurement and risk management coordinator for Surgical Services at the University Hospitals of Leicester NHS Trust. A recent experience illustrated her job's many challenges.

The objective of the current study was to identify QTL conferring resistance to Marek's disease (MD) in commercial layer chickens. To generate the resource population, 2 partially inbred lines that differed in MD-caused mortality were intermated to produce 5 backcross families. Vaccinated chicks were challenged with very virulent plus (vv+) MD virus strain 648A at 6 d and monitored for MD symptoms. A recent field isolate of the MD virus was used because the lines were resistant to commonly used older laboratory strains. Selective genotyping was employed using 81 microsatellites selected based on prior results with selective DNA pooling. Linear regression and Cox proportional hazard models were used to detect associations between marker genotypes and survival. Significance thresholds were validated by simulation. Seven and 6 markers were significant based on proportion of false positive and false discovery rate thresholds less than 0.2, respectively. Seventeen markers were associated with MD survival considering a comparison-wise error rate of 0.10, which is about twice the number expected by chance, indicating that at least some of the associations represent true effects. Thus, the present study shows that loci affecting MD resistance can be mapped in commercial layer lines. More comprehensive studies are under way to confirm and extend these results.

Neurotransmitter release is well known to occur at specialized synaptic regions that include presynaptic active zones and postsynaptic densities. At cholinergic synapses in the chick ciliary ganglion, however, membrane formations and physiological measurements suggest that release distant from postsynaptic densities can activate the predominantly extrasynaptic alpha7 nicotinic receptor subtype. We explored such ectopic neurotransmission with a novel model synapse that combines Monte Carlo simulations with high-resolution serial electron microscopic tomography. Simulated synaptic activity is consistent with experimental recordings of miniature excitatory postsynaptic currents only when ectopic transmission is included in the model, broadening the possibilities for mechanisms of neuronal communication.

The infective larvae (L3i) of the nematode parasite of swine, Oesophagostomum dentatum, are passively ingested by their hosts. The L3i exhibit certain behaviors that are probably selected to increase the likelihood of ingestion, by strategic positioning in the environment. The larvae show positive geotactic behavior and respond to temperature variations in their environment, as shown by their behavior on a thermal gradient. To investigate neuronal control of this behavior, we initiated a study of the structure of the amphidial neurons of this parasite. The same number and types of neuronal dendritic processes are found in the amphids of the O. dentatum L3i as in those of its close relatives Haemonchus contortus and Ancylostoma caninum. Well-developed dendritic processes of wing cells are located in the amphidial sheath cells, these being similar to wing cells AWA in the free-living nematode Caenorhabditis elegans but actually more extensive. Similar to its close relatives just mentioned, and C. elegans as well, O. dentatum L3i has prominent finger cell processes, the finger cell neurons being the thermoreceptors in all 3 of the preceding species. However, unlike the arrangement seen in H. contortus and A. caninum, where the microvilli-like "fingers" of these neurons lie dorsal to the amphidial channel and occupy a very large portion (>50%) of the anterior end of the larva, the dendritic process of the finger cells in O. dentatum extends into unusual linguiform projections that, in turn, extend into the lumen of the mouth tube, a complex structural arrangement that has not been described for any other nematode.

Molecular genetic selection on individual genes is a promising method to genetically improve economically important traits in chickens. A resource population was developed to study the genetics of growth, body composition, skeletal integrity, and metabolism traits. Broiler sires were crossed to dams of 2 diverse, highly inbred lines (Leghorn and Fayoumi), and the F1 birds were intermated by dam line to produce broiler-Leghorn and broiler-Fayoumi F2 offspring. Growth, body composition, skeletal integrity, and hormonal and metabolic factors were measured in 713 F2 individuals. Insulin-like growth factor-I (IGF1) was selected for study as a biological and positional candidate gene. A single nucleotide polymorphism (SNP) was identified between the founder lines in the IGF1 promoter region, and a PCR-RFLP assay was developed. A mixed model was used to statistically analyze associations of IGF1-SNP1 with phenotypic traits. The IGF1-SNP1 had significant associations with most recorded traits, except metabolic traits. Strong interactions between the IGF1 gene and genetic background on growth traits in the 2 F2 populations suggest that genetic interaction is an important aspect for consideration before using the IGF1-SNP1 in marker-assisted selection programs. Several beneficial effects (improved growth, increased breast muscle weight, decreased abdominal fat, and enhanced skeletal integrity) associated with 1 allele indicate the presence of 1 or more loci near IGF1-SNP1 controlling biologically diverse and economically important traits in chickens.

Methylene blue 7.5 mg/kg is frequently given at our institution during parathyroidectomy. The dye preferentially stains the parathyroids so as to provide better surgical visualization. Other than causing a pseudocyanosis, the technique is generally considered to be rather innocuous. We report a case of a patient who, after this procedure, had a postoperative course that was unusual because of slowly resolving altered mental status.

An exercise to standardise glove use across three hospitals uncovered incorrect use of gloves in clinical practice. It also found that a wide range of gloves were being used for different purposes and procured at different costs. This paper explores the reasons and looks at strategies to streamline practice and achieve trust-wide standardisation and cost savings

To determine the role of genetics in baseline lymphocyte parameters, several distinct lines of chickens were examined for differences in peripheral blood leukocyte (PBL) populations. Four highly inbred chicken lines (MHC congenic Fayoumi lines M15.2 and M5.1, and MHC congenic Leghorn lines G-B1 and G-B2), two advanced intercrosses [F5 (Broiler x G-B2) and F5 (Broiler x M15.2)], and an outbred population of broilers were used. Leukocytes isolated from healthy adult birds were labeled with monoclonal antibodies: chCD3, chCD4, chCD8, chBu-1, and hCD14. Flow cytometry was used to determine the total percentage of positively labeled cells for each surface marker in a sample, as well as the mean fluorescent intensity, or surface marker density, of a labeled subset. Significant line differences for percentage positive CD3 T cells and the ratio of B cells:T cells (represented by the Bu-1:CD3 ratio) were found. The effect of line was also significant for CD3 and CD8 T cell receptor density. Effects of sex and MHC on PBL cell surface marker expression were not significant in the lines examined. This study demonstrates the effect of genetic line on resting leukocyte composition of peripheral blood in the chicken lines examined. Observed PBL differences add to our growing knowledge of the varied roles that immune system status (defined by specific cell populations) and genetic background have in determining susceptibility and disease progression in chickens.

Salmonella enteritidis is a foodborne pathogen that negatively affects both animal and human health. Genetic variations in response to pathogenic SE colonization or to SE vaccination were measured in a chicken resource population. Outbred broiler sires and 3 diverse, highly inbred dam lines produced 508 F1 progeny that were evaluated for either bacterial colonization after pathogenic SE inoculation or circulating antibody level after SE vaccination. Five candidate genes were selected for study, based on their biological function as possibly affecting response to SE: toll-like receptor 4 (TLR4), T-cell specific surface protein (CD28), macrophage migration inhibitory factor (MIF), MD-2, and lipopolysaccharide-induced tumor necrosis factor (TNF)-alpha factor (LITAF). Gene fragments were sequenced from the founder lines of the resource population. The LITAF and MIF genes were homozygous for all sires. Single nucleotide polymorphisms (SNP) were identified in 3 genes (TLR4, CD28, and MD-2) and were used to test for associations of sire SNP with SE response. Linear mixed models were used for statistical analyses. The CD28 broiler sire SNP was associated with both bacterial load in the cecum (P < 0.003) and vaccine antibody response (P < 0.05). The MD-2 SNP was associated (P < 0.04) with the bacterial load in the spleen. The use of these SNP in these genes in marker-assisted selection may result in enhancement of disease resistance.

Background: The issue of diagnostic disclosure in dementia has been debated extensively in professional journals, but empirical data concerning disclosure in dementia has not previously been systematically reviewed., Objective: To review empirical data regarding diagnostic disclosure in dementia., Methods: Five electronic databases were searched up to September 2003 (Medline, Embase, Cinahl, Sociological Abstracts, Web of Science). Additional references were identified through hand searches of selected journals and bibliographies of relevant articles and books. The title and abstract of each identified paper were reviewed independently by two reviewers against pre-determined inclusion criteria: original data about disclosure were presented and the paper was in English. Any disagreements were resolved by discussion until consensus was reached. Data were extracted independently by two reviewers using a structured abstraction form. Data quality were not formally assessed although each study was critically reviewed in terms of methodology, sampling criteria, response rates and appropriateness of analysis., Results: Fifty-nine papers met the inclusion criteria for detailed review. Many of the studies had methodological shortcomings. The studies reported wide variability in all areas of beliefs and attitudes to diagnostic disclosure and reported practice. Studies of the impact of disclosure indicate both negative and positive consequences of diagnostic disclosure for people with dementia and their carers., Conclusions: Existing evidence regarding diagnostic disclosure in dementia is both inconsistent and limited with the perspectives of people with dementia being largely neglected. This state of knowledge seems at variance with current guidance about disclosure., (Copyright 2004 John Wiley & Sons, Ltd.)

The objective of this project was to examine the diversity of breast meat composition and quality traits among unique resource populations. Birds from 5 groups (inbred Leghorn, inbred Fayoumi, commercial broilers, F5 broiler-inbred Leghorn cross, and F5 broiler-inbred Fayoumi cross) were utilized. Contemporary stocks (broilers, inbreds, and crosses) were grown in a single house but in separate pens. Birds were harvested at 8 wk of age. Breast muscle weight, moisture, lipid and protein contents, color, pH, and Kramer shear force values were determined on birds from each group. Breasts from broilers contained lower percentages of protein (P < 0.05) and greater percentages of lipid (P < 0.05) compared with all other groups. The 5 genetic stocks did not differ for Hunter L values or pH. The data indicate that the Leghorn inbred line breasts were a more pure and more intense red color than the crossbred contemporary (P < 0.05). Kramer shear force (kg/g sample) was higher (P < 0.05) in breasts from broilers than in breasts from the inbred lines. Our results demonstrate that the 5 genetic groups differed markedly in breast meat composition and quality characteristics. The described outbred by inbred advanced intercross lines will be useful in searches for genes affecting meat quality traits. Definition of the molecular factors that influence these traits will enhance our ability to make improvements in composition and quality of poultry meats.

Seeding biomaterial implants with vascular remnants has the potential to facilitate host vessel ingrowth via a vascular templating effect. Vessels from quail embryo were grown into a polyurethane fibroporous mesh and the samples were frozen-thawed and then implanted in rat subcutaneous dorsum. Results show that the process of revascularization, using the quail vessel remnants, occurred over the first 3 days after implantation and resulted in functional vessels. Rat endothelial cells were found in the quail templates on day 1. On day 2 the endothelial cells formed a confluent layer and started producing laminin. By this time approximately 70% of the rat vessel tissue in the implant had grown into quail vascular remnants, indicating that the quail vessels were extensively used as templates for host vessel ingrowth. Laminin production was increased and collagen production started by day 3, at which time the vessels were functional in that rat blood flowed through them. At 2 weeks host vessel density was approximately twice that of control samples; thus the implant substantially enhanced the size of the vascular network. For meshes that additionally received vascular endothelial growth factor (VEGF) seeding before implantation, vessel density at 2 weeks was enhanced over samples with quail embryo alone. However, the quail was found to have the greatest angiogenic effect above any of the implant components-quail, VEGF, and collagen. Tissue engineering of vessel templates may thus be a realistic solution to effective fast vascularization of biomaterials.

Breeding for disease resistance to Salmonella enteritidis (SE) could be an effective approach to control Salmonella in poultry. The candidate gene approach is a useful method to investigate genes that are involved in genetic resistance. In this study, 12 candidate genes that are involved in the pathogenesis of Salmonella infection were investigated using five different genetic groups of meat-type chicken. The genes were natural resistance associated macrophage protein 1 (SLC11A1, previously known as NRAMP1), inhibitor of apoptosis protein 1 (IAP1), prosaposin (PSAP), Caspase-1 (CASP1), inducible nitric oxide production (iNOS), interferon-gamma (IFNG), interleukin-2 (IL2), immunoglobulin light chain (IGL), ZOV3, and transforming growth factors B2, B3 and B4 (TGFB2, B3 and B4). In total, 117 birds of all groups were challenged with SE at the age of 3 weeks. In all birds at 7-day post-infection SE load in caecum content, spleen and liver were quantified. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays were used to genotype all animals for each gene. Overall we found the most significant associations with caecum content, nine of 12 genes showed a significant association (SLC11A1, IAP1, PSAP, CASP1, iNOS, IL2, IGL, TGFB2 and TGFB4). For liver, five genes (SLC11A1, CASP1, IL2, IGL, and TGFB4) and for spleen, only one gene (TGFB3) showed a significant association with SE load. By showing associations of 12 PCR-RFLP assays with SE load after a pathogen challenge, this study confirmed the polygenic nature of disease resistance to SE.

A potential limitation of the use of a dominant molecular marker system such as DNA fingerprinting (DFP) is the inability to distinguish homozygous from heterozygous allele state in an individual, and a resulting inaccuracy in estimating effects of the marker alleles. The objective of this study was to accurately estimate the effect of DFP markers on egg-production traits. A BC1 population was produced from two distinct layer lines. Four DFP bands, each originating predominantly in one of the two parental lines, were evaluated for linkage with egg-production quantitative trait loci in the BC1 population. The egg-production traits consisted of eight early period and seven late period measurements. Eight marker-trait linkages were identified out of 60 total statistical tests. By utilizing information on frequency of DFP bands in two parental lines, selecting F1 sires with DFP bands present, and backcrossing to the line lacking these bands, the population design allowed definitive identification of the DFP zygosity in the BC1 resource population hens. In this manner, accurate estimates of marker allele effects on egg-production traits were obtained from the dominant marker system of DNA fingerprinting.

Antibody responses (primary and secondary phases) were measured in an F2 population. The resource population was derived from grandsires of two highly inbred major histocompatibility complex (MHC)-congenic Fayoumi chicken lines (named M5.1 and M15.2) mated with highly inbred Leghorn G-B1 hens. Secondary phase parameters of maximum titres (Ymax) and time required to achieve Ymax (Tmax) were estimated from post-secondary titres by using a non-linear regression model. Associations of single nucleotide polymorphisms (SNP) in transforming growth factor beta2 (TGFB2), 3, and 4 genes with antibody response parameters were evaluated. Multiple immune response parameters were significantly associated with the TGFB2 gene primarily in the lineage of the M5.1 grandsire, suggesting that TGFB2 or linked genes affect antibody response in hens. Significant main effects of the three genes were mostly found in the lineage of the M5.1 grandsire. Significant two-way interactions on antibody response were primarily detected between TGFB3 and TGFB4 genes, and in the lineage of the M15.2 grandsire. Effects preferentially detectable in only one of the MHC-congenic lineages suggest that there was interaction between the MHC and TGFB genes. The characterized TGFB SNPs might be applied in marker-assisted selection to improve antibody production.

The chicken B-cell marker (ChB6), caspase-1, inhibitor of apoptosis protein-1 (IAP-1), interleukin-15 receptor alpha-chain (IL-15Ralpha), interleukin-2 receptor gamma-chain (IL-2Rgamma), and immunoglobulin supfamily gene (ZOV3), as physiological candidate genes for chicken immune response, were selected to investigate associations with antibody kinetics to SRBC and killed B. abortus. An F2 population was derived from mating highly inbred (>99%) males of two MHC-congenic Fayoumi lines (named M5.1 and M15.2) with G-B1 Leghorn hens. Antibody response to SRBC and B. abortus after immunization at 19 and 22 wk were measured. Secondary phase parameters of maximum titers (Ymax) and time required to achieve Ymax (Tmax) were estimated from postsecondary titers by using a nonlinear regression model. The DNA polymorphisms of six genes were identified, and associations of single nucleotide polymorphisms (SNP) in the six genes with antibody response parameters were analyzed. Significant main effects of the gene polymorphisms were mostly found in the lineage of the M5.1 grandsire and primarily on antibody response to B. abortus. There was general agreement of allelic effect within antibody parameters among genes. These results suggest that the SNP characterized in the study may serve as markers for genetic enhancement of humoral immune capacity in the chicken.

The ability to answer some of the questions of fundamental interest in functional genetics depends upon the utilization of appropriate and sometimes quite novel population designs. We will explore examples of how unique population designs of varied complexity can be used to explore questions, such as the following. What is the number of genes controlling different biological traits? Can streamlined genetics at the whole-animal level help to dissect complex genetic traits? Are there beneficial alleles "hiding" in undeveloped lines? To what extent is the expression of a specific gene modified by interactions with other genes in the population? Unique genetic resources, combined with novel experimental designs and contemporary analytical techniques, provide exceptional opportunities to explore both fundamental and practical questions in biological sciences.