Gene expression profiling of Naïve sheep genetically resistant and susceptible to gastrointestinal nematodes

BACKGROUND: Gastrointestinal nematodes constitute a major cause of morbidity and mortality in grazing ruminants. Individual animals or breeds, however, are known to differ in their resistance to infection. Gene expression profiling allows us to examine large numbers of transcripts simultaneously in order to identify those transcripts that contribute to an animal's susceptibility or resistance. RESULTS: With the goal of identifying genes with a differential pattern of expression between sheep genetically resistant and susceptible to gastrointestinal nematodes, a 20,000 spot ovine cDNA microarray was constructed. This array was used to interrogate the expression of 9,238 known genes in duodenum tissue of four resistant and four susceptible female lambs. Naïve animals were used in order to look at genes that were differentially expressed in the absence of infection with gastrointestinal nematodes. Forty one unique known genes were identified that were differentially expressed between the resistant and susceptible animals. Northern blotting of a selection of the genes confirmed differential expression. The differentially expressed genes had a variety of functions, although many genes relating to the stress response and response to stimulus were more highly expressed in the susceptible animals. CONCLUSION: We have constructed the first reported ovine microarray and used this array to examine gene expression in lambs genetically resistant and susceptible to gastrointestinal nematode infection. This study indicates that susceptible animals appear to be generating a hyper-sensitive immune response to non-nematode challenges. The gastrointestinal tract of susceptible animals is therefore under stress and compromised even in the absence of gastrointestinal nematodes. These factors may contribute to the genetic susceptibility of these animals

Liaison psychiatry—measurement and evaluation of service types, referral patterns and outcomes (LP-MAESTRO): a protocol

Introduction: We describe the protocol for a project that will use linkage of routinely collected NHS data to answer a question about the nature and effectiveness of liaison psychiatry services in acute hospitals in England. Methods and analysis: The project will use three data sources: (1) Hospital Episode Statistics (HES), a database controlled by NHS Digital that contains patient data relating to emergency department (ED), inpatient and outpatient episodes at hospitals in England; (2) ResearchOne, a research database controlled by The Phoenix Partnership (TPP) that contains patient data relating to primary care provided by organisations using the SystmOne clinical information system and (3) clinical databases controlled by mental health trusts that contain patient data relating to care provided by liaison psychiatry services. We will link patient data from these sources to construct care pathways for patients who have been admitted to a particular hospital and determine those patients who have been seen by a liaison psychiatry service during their admission. Patient care pathways will form the basis of a matched cohort design to test the effectiveness of liaison intervention. We will combine healthcare utilisation within care pathways using cost figures from national databases. We will compare the cost of each care pathway and the impact of a broad set of health-related outcomes to obtain preliminary estimates of cost-effectiveness for liaison psychiatry services. We will carry out an exploratory incremental cost-effectiveness analysis from a whole system perspective. Ethics and dissemination: Individual patient consent will not be feasible for this study. Favourable ethical opinion has been obtained from the NHS Research Ethics Committee (North of Scotland) (REF: 16/NS/0025) for Work Stream 2 (phase 1) of the Liaison psychiatry—measurement and evaluation of service types, referral patterns and outcomes study. The Confidentiality Advisory Group at the Health Research Authority determined that Section 251 approval under Regulation 5 of the Health Service (Control of Patient Information) Regulations 2002 was not required for the study ‘on the basis that there is no disclosure of patient identifiable data without consent’ (REF: 16/CAG/0037). Results of the study will be published in academic journals in health services research and mental health. Details of the study methodology will also be published in an academic journal. Discussion papers will be authored for health service commissioners

The nature and activity of liaison mental services in acute hospital settings: a multi-site cross sectional study

Background: To describe the clinical activity patterns and nature of interventions of hospital-based liaison psychiatry services in England. Methods: Multi-site, cross-sectional survey. 18 acute hospitals across England with a liaison psychiatry service. All liaison staff members, at each hospital site, recorded data on each patient they had face to face contact with, over a 7 day period. Data included location of referral, source of referral, main clinical problem, type of liaison intervention employed, staff professional group and grade, referral onto other services, and standard assessment measures. Results: A total of 1475 face to face contacts from 18 hospitals were included in the analysis, of which approximately half were follow-up reviews. There was considerable variation across sites, related to the volume of Emergency Department (ED) attendances, number of hospital admissions, and work hours of the team but not to the size of the hospital (number of beds). The most common clinical problems were co-morbid physical and psychiatric symptoms, self-harm and cognitive impairment. The main types of intervention delivered were diagnosis/formulation, risk management and advice. There were differences in the type of clinical problems seen by the services between EDs and wards, and also differences between the work conducted by doctors and nurses. Almost half of the contacts were for continuing care, rather than assessment. Eight per cent of all referrals were offered follow up with the LP team, and approximately 37% were referred to community or other services. Conclusions: The activity of LP services is related to the flow of patients through an acute hospital. In addition to initial assessments, services provide a wide range of differing interventions, with nurses and doctors carrying out distinctly different roles within the team. The results show the volume and diversity of LP work. While much clinical contact is acute and confined to the inpatient episode, the LP service is not defined solely by an assessment and discharge function; cases are often complex and nearly half were referred for follow up including liaison team follow up

The SNAPSHOT study protocol : SNAcking, Physical activity, Self-regulation, and Heart rate Over Time

Peer reviewedPublisher PD

Pan-viral serology implicates enteroviruses in acute flaccid myelitis.

Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM)1-6. Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF)2. CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan). Metagenomic next-generation sequencing (mNGS) of AFM CSF RNA (n = 20 cases) was also performed, both unbiased sequencing and with targeted enrichment for EVs. Using VirScan, the viral family significantly enriched by the CSF of AFM cases relative to controls was Picornaviridae, with the most enriched Picornaviridae peptides belonging to the genus Enterovirus (n = 29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (n = 22/26 cases versus 7/50 controls). mNGS did not detect additional EV RNA. Despite rare detection of EV RNA, pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM

Substance use disorders in women with anorexia nervosa

Objective: We examined prevalence of in women substance use disorders (SUID) with: (1) anorexia nervosa (AN) restricting type (RAN); (2) AN with purging only (PAN); (3) AN with binge eating only (BAN); and (4) lifetime AN and bulimia nervosa (ANBN). Secondary analyses examined SUD related to lifetime purging behavior and lifetime binge eating. Method: Participants (N = 731) were drawn from the international Price Foundation Genetic Studies. Results: The prevalence of SUD differed across AN subtypes, with more in the ANBN group reporting SUD than those in the RAN and PAN groups. individuals who purged were more likely to report substance use than those who did not purge. Prevalence of SUD differed across lifetime binge eating status. Discussion: SUD are common in AN and are associated with bulimic symptomatology. Results underscore the het-erogeneity in AN, highlighting the importance of screening for SUD across AN subtype

Discovery of quantitative trait loci for resistance to parasitic nematode infection in sheep: I. Analysis of outcross pedigrees

BACKGROUND: Currently most pastoral farmers rely on anthelmintic drenches to control gastrointestinal parasitic nematodes in sheep. Resistance to anthelmintics is rapidly increasing in nematode populations such that on some farms none of the drench families are now completely effective. It is well established that host resistance to nematode infection is a moderately heritable trait. This study was undertaken to identify regions of the genome, quantitative trait loci (QTL) that contain genes affecting resistance to parasitic nematodes. RESULTS: Rams obtained from crossing nematode parasite resistant and susceptible selection lines were used to derive five large half-sib families comprising between 348 and 101 offspring per sire. Total offspring comprised 940 lambs. Extensive measurements for a range of parasite burden and immune function traits in all offspring allowed each lamb in each pedigree to be ranked for relative resistance to nematode parasites. Initially the 22 most resistant and 22 most susceptible progeny from each pedigree were used in a genome scan that used 203 microsatellite markers spread across all sheep autosomes. This study identified 9 chromosomes with regions showing sufficient linkage to warrant the genotyping of all offspring. After genotyping all offspring with markers covering Chromosomes 1, 3, 4, 5, 8, 12, 13, 22 and 23, the telomeric end of chromosome 8 was identified as having a significant QTL for parasite resistance as measured by the number of Trichostrongylus spp. adults in the abomasum and small intestine at the end of the second parasite challenge. Two further QTL for associated immune function traits of total serum IgE and T. colubiformis specific serum IgG, at the end of the second parasite challenge, were identified on chromosome 23. CONCLUSION: Despite parasite resistance being a moderately heritable trait, this large study was able to identify only a single significant QTL associated with it. The QTL concerned adult parasite burdens at the end of the second parasite challenge when the lambs were approximately 6 months old. Our failure to discover more QTL suggests that most of the genes controlling this trait are of relatively small effect. The large number of suggestive QTL discovered (more than one per family per trait than would be expected by chance) also supports this conclusion

Using comparative genomics to reorder the human genome sequence into a virtual sheep genome

Using BAC-end sequences, a sparse marker map and the sequences of the human, dog and cow genomes, an accurate and detailed sub-gene level map of the sheep genome has been constructed

Is season of birth related to disordered eating and personality in women with eating disorders?

We assessed the relation between season of birth and eating disorder symptoms and personality characteristics in a sample of 880 women with eating disorders and 580 controls from two Price Foundation Studies. Eating disorder symptoms were assessed using the Structured Interview of Anorexic and Bulimic Disorders and the Structured Clinical Interview for DSM-IV. Personality traits were assessed using the Temperament and Character Inventory and the Frost Multidimensional Perfectionism Scale. Date of birth was obtained from a sociodemographic questionnaire. No significant differences were observed 1) in season of birth across eating disorder subtypes and controls; nor 2) for any clinical or personality variables and season of birth. We found no evidence of season of birth variation in eating disorders symptoms or personality traits. Contributing to previous conflicting findings, the present results do not support a season of birth hypothesis for eating disorders

Experiences of people seen in an acute hospital setting by a liaison mental health service: responses from an online survey

Background- In recent years the UK has expanded the provision of liaison mental health services (LMHS). Little work has been undertaken to explore first-hand experiences of them. Aims- The aim of this study was to gain insights into the experiences of users of LMHS in both emergency departments and acute inpatient wards in the UK. Methods- This cross-sectional internet survey was initially advertised from May-July 2017 using the social media platform Facebook. Due to a paucity of male respondents, it was re-run from November 2017-February 2018, specifically targeting male respondents. The survey featured a structured questionnaire divided into three categories: the profile of the respondent, perceived professionalism of LMHS and overall opinion of the service. Analysis- Responses to the structured questionnaire were analysed using descriptive statistics and latent class analysis. Free-text responses were transcribed verbatim and interpreted using thematic analysis. Results- 184 people responded to the survey. 147 were service users and 37 were partners, friends or family members of service users. Only 31% of service users and 27% of close others found their overall contact helpful. Latent class analysis identified three clusters − 46% of service users generally disliked their contact, 36% had an overall positive experience, and 18% did not answer most questions about helpfulness or usefulness. Features most frequently identified as important were the provision of a 24/7 service, assessment by a variety of healthcare professionals and national standardisation of services. Respondents indicated that the least important feature was the provision of a separate service for older people. They desired faster assessments following referral from the parent team, clearer communication about next steps and greater knowledge of local services and third sector organisations. Conclusions- This survey identified mixed responses, but overall experiences were more negative than indicated in the limited previous research. The evaluation and adaptation of LMHS along the lines suggested in our survey should be prioritised to enhance their inherent therapeutic value and to improve engagement with treatment and future psychiatric care