Midlothian Community Hospital

In mammals, Mda5 and RIG-I are members of the evolutionary conserved RIG-like helicase family that play critical roles in the outcome of RNA virus infections. Resolving influenza infection in mammals has been shown to require RIG-I; however, the apparent absence of a RIG-I homolog in chickens raises intriguing questions regarding how this species deals with influenza virus infection. Although chickens are able to resolve certain strains of influenza, they are highly susceptible to others, such as highly pathogenic avian influenza H5N1. Understanding RIG-like helicases in the chicken is of critical importance, especially for developing new therapeutics that may use these systems. With this in mind, we investigated the RIG-like helicase Mda5 in the chicken. We have identified a chicken Mda5 homolog (ChMda5) and assessed its functional activities that relate to antiviral responses. Like mammalian Mda5, ChMda5 expression is upregulated in response to dsRNA stimulation and following IFN activation of cells. Furthermore, RNA interference-mediated knockdown of ChMda5 showed that ChMda5 plays an important role in the IFN response of chicken cells to dsRNA. Intriguingly, although ChMda5 levels are highly upregulated during influenza infection, knockdown of ChMda5 expression does not appear to impact influenza proliferation. Collectively, although Mda5 is functionally active in the chicken, the absence of an apparent RIG-I-like function may contribute to the chicken's susceptibility to highly pathogenic influenza.

INTRODUCTION: although drug-related problems (DRPs) are known to be prevalent in elderly patients, the literature on prevention of iatrogenic disease is sparse. The present study addresses this requirement. OBJECTIVES: to assess the incidence of DRPs in elderly patients admitted to Tayside hospitals before (phase I) and after (phase II) implementation of preventive strategies. DESIGN: all elderly people admitted to hospital were screened by a pharmacist; individual case reviews were prepared for all those with a potential DRP and reviewed by a three-member panel which made a final decision on the presence of a DRP and its contribution to admission. SETTING: all hospital wards admitting elderly patients in the Tayside region of Scotland. SUBJECTS: 1011 elderly patient admissions over a 9-month period (phase I); 857 elderly patient admissions over an 8-month period (phase II). MAIN OUTCOME MEASURES: incidence of DRPs before and after targeted intervention strategies (information bulletin for general practitioners, patient information leaflet, oral presentation to trainee general practitioners). RESULTS: in phase I, the incidence of DRPs was 144/1011 (14.2%), with 54/1011 (5.3%) of the admissions identified as being definitely or probably drug-related. Non-steroidal anti-inflammatory drugs (NSAIDs) were the main drug group involved, being responsible for 15/54 (28%) of admissions primarily due to a DRP. Over 66% of admissions due to adverse effects of NSAIDs were considered to be definitely preventable. In phase II, after targeted intervention strategies, there was no significant reduction in total incidence of DRPs or incidence of DRPs related to NSAIDs. However, there appeared to be an improvement in the first 4 months, and a significant drop in NSAID prescribing in Tayside compared with the rest of Scotland was observed. CONCLUSION: DRPs remain a significant problem in elderly patients and NSAIDs are the major contributor. The intervention strategies used in the study were not demonstrably effective, but a continuous programme of education may be necessary to limit NSAID use.

The effects of a mindfulness-based procedure, called Meditation on the Soles of the Feet, were evaluated as a cognitive-behavioral intervention for physical aggression in 6 offenders with mild intellectual disabilities. They were taught a simple meditation technique that required them to shift their attention and awareness from the precursors of aggression to the soles of their feet, a neutral point on their body. Results showed that physical and verbal aggression decreased substantially, no Stat medication or physical restraint was required, and there were no staff or peer injuries. Benefit-cost analysis of lost days of work and cost of medical and rehabilitation because of injury caused by these individuals in both the 12 months prior to and following mindfulness-based training showed a 95.7% reduction in costs. This study suggests that this procedure may be a clinically effective and cost-effective method of enabling adult offenders with intellectual disabilities to control their aggression.

It is now 18 years since the first identification of a case of vCJD in the UK. Since that time, there has been much speculation over how vCJD might impact human health. To date there have been 177 case reports in the UK and a further 51 cases worldwide in 11 different countries. Since establishing that BSE and vCJD are of the same strain of agent, we have also shown that there is broad similarity between UK and non-UK vCJD cases on first passage to mice. Transgenic mouse studies have indicated that all codon 129 genotypes are susceptible to vCJD and that genotype may influence whether disease appears in a clinical or asymptomatic form, supported by the appearance of the first case of potential asymptomatic vCJD infection in a PRNP 129MV patient. Following evidence of blood transfusion as a route of transmission, we have ascertained that all blood components and leucoreduced blood in a sheep model of vCJD have the ability to transmit disease. Importantly, we recently established that a PRNP 129MV patient blood recipient with an asymptomatic infection and limited PrP(Sc) deposition in the spleen could readily transmit disease into mice, demonstrating the potential for peripheral infection in the absence of clinical disease. This, along with the recent appendix survey which identified 16 positive appendices in a study of 32,441 cases, underlines the importance of continued CJD surveillance and maintaining control measures already in place to protect human health.

Because feed intake is controlled in broiler breeders, amino acid supply is determined by the composition of the feed and the level of feed intake. Controlling amino acid supply during the laying cycle can be facilitated by the use of a model for calculating requirements. A possible model is outlined and the various components discussed. Typical calculations suggest that the model can provide a useful basis for practical feeding decisions. Model elements include: levels of animal performance; utilization of amino acids for egg production, maintenance, and tissue growth; population structure; and the variation of feed intake and the covariance between feed intake and requirements.

BACKGROUND: Ischemic heart disease (IHD) is a leading cause of morbidity and mortality in both developing and developed countries. An underlying cause of IHD involves retention and deposit of serum lipids in coronary arteries, decreasing blood flow. Drugs (conventional and herbal) are used to lower levels of serum cholesterol to help prevent IHD. The Ayurvedic medicine pharmacopoeia identified herbs that might contribute to a decrease in cholesterol and therefore reduce the risk of IHD. METHODS: Literature searches were conducted at 3 points: 2003, 2004, and 2007. Databases searched included PubMed, the National Library of Medicine, the National Center for Complementary and Alternative Medicine, Ovid, and EBSCO Information Services, and other search strategies also were used. Each article was assessed for quality by 3 people, and discrepancies were resolved by arbitration using a fourth person, who also read and scored each article. Additional assessments of safety using a scale and determination of reported efficacy/effectiveness of the randomized controlled trials (RCTs) and quasi-experimental designs (QEDs) were made. RESULTS: RCTs generally received high quality scores and improved by decade of publication. More than 50% of garlic, more than 80% of guggul, and 100% of Arjuna RCTs reported product effectiveness. Safety scores did not improve by decade. The QEDs received medium and high quality scores, and 93% of them reported effectiveness. The QEDs had a higher mean score for safety reporting than the RCTs. CONCLUSIONS: Many studies received high quality scores and noted safety information and reported effectiveness or efficacy in a clear manner. This finding was not consistent with other systematic reviews that have found the highest reported efficacy/ effectiveness in studies of poorer quality. Ayurvedic herbs reviewed here should be considered by physicians when trying to manage hyperlipidemia in their patients.

Proliferative enteropathy is caused by the microaerophilic obligate intracellular bacterium ileal symbiont (IS) intracellularis. Treatment of this disease is problematic because of the lack of in vivo or in vitro data on the activities of antimicrobial agents. A new procedure for determining the susceptibility of IS intracellularis was developed by using a tissue culture system which promotes the in vitro multiplication of this organism. Nineteen antimicrobial agents were evaluated in triplicate cultures for their intracellular and extracellular activities against up to three IS intracellularis strains isolated from pigs with proliferative enteropathy. The MIC was defined as the lowest concentration which prevented multiplication of 99% of the IS intracellularis isolates. Penicillin, erythromycin, difloxacin, virginiamycin, and chlortetracycline were the most active compounds tested, all with MICs of < or = 1 microgram/ml. Tiamulin and tilmicosin were the next most active compounds, with MICs of < or = 4 micrograms/ml. The MICs of aminoglycosides were generally > 32 micrograms/ml. Both lincomycin and tylosin were relatively inactive against the IS intracellularis strains tested, with MICs of 32 and 64 micrograms/ml, respectively. These results indicate that some compounds capable of intracytoplasmic accumulation and blocking bacterial protein synthesis were active against IS intracellularis strains isolated from pigs with proliferative enteropathy. The in vitro cultivation system shows promise as a method for studying the interaction between IS intracellularis and antimicrobial agents and for screening new antibiotics for use in therapy.

This work provides a detailed account of word level pronunciation in England and Scotland between 1700 and 1900. All major and minor source materials are presented in depth and there is a close discus

In the latter part of 1991 an unusual neurological disease was recognised on several farms in England. This report describes the case histories and clinical, biochemical and pathological findings in six calves and two lambs aged from two to 44 weeks obtained from five of these farms. Laminar cerebrocortical necrosis and severe bilateral necrosis of the thalamus and/or striatum progressing to cavitation were recognised in their brains. These changes are similar to those of experimental sulphate toxicity. Morbidity rates of 16 to 48 per cent and mortality rates of 0 to 8 per cent were recorded. The affected animals did not respond to vitamin B1 treatment; the erythrocyte transketolase levels of in-contact cattle and of one untreated affected calf and one untreated lamb were within the normal range. All five farms had recently introduced a proprietary concentrate ration containing ammonium bicarbonate. After this ration was withdrawn no new cases of nervous clinical disease were observed. It is suggested that, in at least some cases, the morphology and topography of lesions may distinguish sulphate induced polioencephalomalacia from that of sporadic thiamine-dependent cerebrocortical necrosis.

The authors investigated changes in treatment team functioning in an adult inpatient psychiatric hospital after the implementation of a mindfulness-based mentoring intervention. Using a multiple baseline across treatment teams design, the authors assessed levels of functioning of three treatment teams using a 50-item rating scale and then introduced mindfulness-based mentoring successively across the treatment teams. Following intervention, four follow-up assessments at 3-month intervals were undertaken to assess the durability of the enhanced treatment team functioning levels in the absence of mentoring. Results showed that with the introduction of mindfulness-based mentoring, treatment team performance was enhanced, patients'attendance at therapeutic groups and individual therapy sessions was maximized, and patient and staff satisfaction with treatment team functioning was substantially increased, with patient satisfaction showing greater gains than staff satisfaction. Mindfulness-based mentoring may be an efficient and effective intervention for enhancing and maintaining the performance of treatment teams in adult psychiatric hospitals.

A simple process for batch or continuous formation of polymer nanofibers and other nanomaterials in the bulk of a sheared fluid medium is introduced. The process may be of high value to commercial nanotechnology, as it can be easily scaled up to the fabrication of staple nanofibers at rates that may exceed tens of kilograms per hour. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

BACKGROUND: Dementia is a major cause of disability among older people and constitutes one of the greatest challenges currently facing families and health and social care services in the developed world. In response to trends in dementia prevalence and the impact the condition has on peoples' lives, dementia care has been placed high on the public and political agenda in the United Kingdom. However, despite significant public resources being allocated to combat the impact of the disease, recent evidence indicates that numerous challenges in relation to service provision remain. This study aimed to develop a deeper understanding of the lived experience of people with dementia regarding their service-related needs. METHOD: The study made use of data gathered through individual semi-structured, narrative interviews conducted with persons with experience of dementia and their unpaid carers. RESULTS: Although participants were generally satisfied with the services they received, a number of unmet needs related to service provision were identified. In terms of diagnostic procedures the findings of this study indicate the need for early diagnosis delivered through a comprehensive assessment package. The participants also highlighted the need for well-coordinated post-diagnostic support, greater continuity of care concerning the personnel involved, and enhanced access to non-pharmacological interventions to support identity and social engagement. CONCLUSION: This study contributes to a better understanding of service-related needs of people with dementia in relation to diagnostic procedures and post-diagnostic support.

The immunoregulatory cytokine transforming growth factor (TGF)-beta(1) is secreted as a biologically inactive complex with latency-associated peptide, which must be modified by local factors to expose the functionally active cytokine. The epithelial integrin alpha(v)beta(6) mediates local activation of TGF-beta(1) in the lung and beta(6)(-/-) mice exhibit exaggerated pulmonary inflammation, but their response to inflammatory stimuli in the gut has not been investigated. We found that both beta(6) and TGF-beta(1) are constitutively expressed in the jejunal epithelial compartment in uninfected mice and during infection with the intestinal nematode Nippostrongylus brasiliensis. We also present data showing that beta(6)(-/-) mice are seriously compromised in their ability to mount a mucosal mast cell response after infection, and there is a significant reduction in the expression and systemic release of the granule chymase, mouse mast cell protease-1. Because in vitro expression of this chymase is regulated by TGF-beta(1), these data indicate that in the absence of alpha(v)beta(6) epithelially expressed TGF-beta(1) may not be activated, with a consequent absence of expression of mouse mast cell protease-1 and down-regulation of the mucosal mast cell response.

The Questions About Behavioral Function (QABF), a 25-item rating scale, was developed to identify the function(s) of maladaptive behavior in individuals with developmental disabilities. The authors adapted it for use with individuals with serious mental illness who engage in maladaptive behavior and assessed the psychometric characteristics of the new scale (Questions About Behavioral Function in Mental Illness; QABF-MI) in a sample of 135 adults with serious mental illness from three inpatient psychiatric hospitals. Staff most familiar with each person rated each item on a 5-point Likert-type rating scale, and the ratings were subjected to a number of psychometric analyses. The results of factor analyses provided a conceptually meaningful five-factor solution: physical discomfort, social attention, tangible reinforcement, escape, and nonsocial reinforcement. Congruence between the five factors derived with the QABF-MI and the corresponding factors in the original QABF was perfect. The results indicated that the QABF-MI has robust psychometric properties and may be useful as a screening tool for determining the nature of the variables that maintain maladaptive behavior exhibited by individuals with serious mental illness.

Sonic hedgehog plays an essential role in maintaining hepatoblasts in a proliferative non-differentiating state during embryogenesis. Transduction of the Hedgehog signaling pathway is dependent on the presence of functional primary cilia and hepatoblasts, therefore, must require primary cilia for normal function. In congenital syndromes in which cilia are absent or non-functional (ciliopathies) hepatorenal fibrocystic disease is common and primarily characterized by ductal plate malformations which underlie the formation of liver cysts, as well as less commonly, by hepatic fibrosis, although a role for abnormal Hedgehog signal transduction has not been implicated in these phenotypes. We have examined liver, lung and rib development in the talpid(3) chicken mutant, a ciliopathy model in which abnormal Hedgehog signaling is well characterized. We find that the talpid(3) phenotype closely models that of human short-rib polydactyly syndromes which are caused by the loss of cilia, and exhibit hypoplastic lungs and liver failure. Through an analysis of liver and lung development in the talpid(3) chicken, we propose that cilia in the liver are essential for the transduction of Hedgehog signaling during hepatic development. The talpid(3) chicken represents a useful resource in furthering our understanding of the pathology of ciliopathies beyond the treatment of thoracic insufficiency as well as generating insights into the role Hedgehog signaling in hepatic development.

PURPOSE: To identify factors associated with decreased muscle strength and activity after anterior cruciate ligament (ACL) reconstruction with semitendinosus-gracilis tendon (ST-G) grafts. TYPE OF STUDY: Retrospective review. METHODS: Eighty-five patients who underwent ACL reconstruction with ST-G grafts were evaluated at a mean of 44.4 months after surgery. Patients underwent isokinetic testing, physical examination, radiographs, instrumented laxity testing, and Lysholm, Cincinnati, and International Knee Documentation Committee (IKDC) ratings. Cartilage and meniscal pathology at surgery was reviewed. Strength group 1 (n = 30) showed greater than 20% deficits in strength; strength group 2 (n = 55) had less than 20% strength deficits. Activity group 1 (n = 60) maintained their IKDC activity level at final follow-up relative to preinjury level; activity group 2 (n = 25) decreased activity by 1 or more levels. RESULTS: With all patients combined, there was less than a 4% difference in mean hamstring and quadriceps strength between the reconstructed and contralateral legs at follow-up. Knee flexion deficits were associated with decreased hamstring strength. Subjective giving way and squatting/kneeling discomfort were associated with decreased quadriceps strength. Patients in strength group 1 were more likely to have squatting/kneeling discomfort and lower Cincinnati Function scores. Activity group 2 had a longer interval from injury to surgery and more chondromalacia at surgery. At follow-up, activity group 2 had lower subjective scores and was more likely to have pain, swelling, giving way, and flexion deficits. Activity group 2 also had greater deficits in quadriceps strength. CONCLUSIONS: Articular cartilage injury and meniscal pathology were not associated with decreased muscle strength. ACL reconstruction with ST-G grafts has a 38% incidence of squatting/kneeling pain that occurs secondary to patellofemoral crepitus, harvest site symptoms, and tibial hardware sensitivity. LEVEL OF EVIDENCE: Level IV, therapeutic, case series, no control group.

OBJECTIVE: Mice divergently selected for high or low food intake (FI) at constant body mass differ in their resting metabolic rates (RMRs). Low-intake individuals (ML) have significantly lower RMR (by 30%) compared with those from the high-intake line (MH). We hypothesized that MLs might, therefore, be more likely to increase their body and fat mass when exposed to a high-fat diet (HFD). RESEARCH METHODS AND PROCEDURES: We exposed both lines to a diet with 44.9% calories from fat for 3 weeks while measuring FI, fecal production, and body mass and then returned the mice to standard chow. RESULTS: When exposed to the HFD, both lines significantly decreased their FI (MH, 40% to 45%; ML, 31% to 35%). This decrease occurred simultaneously with a significant increase in apparent energy absorption efficiency (AEAE). When returned to chow, FI and AEAE returned to the levels observed prior to HFD exposure. Because of the adjustments in FI, the absorbed energy was maintained in the MLs and, thus, body mass remained constant. The MH individuals overcompensated for the elevated energy content and AEAE on the HFD and, therefore, absorbed lower energy than when feeding on chow. These mice also did not significantly change their body mass when on the HFD and must have made adjustments in their energy expenditures. Both lines and both sexes increased in fat content on the HFD, but these effects were not different between lines or sexes. DISCUSSION: We found no support for the hypothesis that mice with low RMRs were more susceptible to weight gain when fed the HFD.

Abstract 1. The paper reviewed the history of the power of selection, the response of breeders to clear objectives, and the evolution and application of focused technology in the breeding of meat‐type chicken. 2. It was declared that the breeding industry has been shaped by four major driving forces, namely: cost reduction, quality, versatility and ethical considerations. 3. The impact of these forces on the breeding industry over the last four decades are reviewed and the challenge of future developments considered. Notes This lecture, the tenth given in memory of the late Dr R. F. Gordon, was delivered at The London School of Pharmacy, on the 9th of April, 1992.

A 40 year old man was admitted with a four week history of intractable diarrhoea and abdominal pain. A clinical diagnosis of inflammatory bowel disease was supported by biopsies of colonic mucosa. There was no response to Mesalazine and over 12 days the patient became critically ill with diarrhoea, hypovolaemia, and peritonism. A laparotomy was performed and 130 cm of infarcted ileum was resected. Extensive investigations excluded thrombophilia and echocardiography excluded intracardiac thrombus. Postoperatively the patient continued to have diarrhoea and he was diagnosed with coeliac disease on the basis of positive antiendomysial and antitissue transglutaminase autoantibodies and duodenal histology. Although there is no proof that mesenteric infarction occurred as a direct consequence of coeliac disease, clinicians should be aware of this possibility.

Sections Lanatuli and Atramentarii of the genus Coprinopsis contain some of the best known and most important agaric species, including C. cinerea and C. lagopus, yet a critical, phylogeny-based assessment of the species limits has not been carried out. Taxa have been characterized chiefly on the basis of morphological characters, which however show little discriminatory power and/or considerable overlap between several species pairs. We used ITS and LSU sequence data of 29 described taxa in Coprinopsis sections Lanatuli and Atramentarii to infer species limits and the correspondence between morphological characters and species lineages, as well as to examine the phylogenetic affinities of sections Lanatuli and Atramentarii. Our analyses recovered three large clades, implying a paraphyly for section Lanatuli. Based on morphology and clade structure, we estimate ca. 38 species in the two sections, including several potentially new taxa, three of which are described herein. Coprinopsis pachyderma, C. lagopus var. vacillans, C. acuminata, C. spelaiophila, Coprinus citrinovelatus and Cop. brunneistrangulatus were found to be synonymous with other, earlier described species. Congruent with previous mating studies, our analyses recovered multiple, morphologically indistinguishable lineages within C. lagopus, which included C. lagopus var. vacillans, an ephemeral, developmental variant. Morphological traits supporting the inferred clade structure are discussed. Three new taxa (C. fusispora, C. babosiae, C. villosa), and one new combination (C. mitraespora) are proposed.