96 research outputs found

    ‘Breaking good news’: neurologists’ experiences of discussing SUDEP with patients in Scotland

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    Since the findings of a Fatal Accident Inquiry (FAI) in 2010, clinicians working in Scotland have been advised to discuss the risk of Sudden Unexpected Death in Epilepsy (SUDEP) with patients immediately or soon after a diagnosis of epilepsy is made. A thematic analysis was used to describe the experiences discussing SUDEP of 10 clinicians (six Consultant Neurologists and four Neurology Registrars) working in Scotland. Five themes were found: Clinicians employ a ‘SUDEP protocol’, suggesting there is a standardised way of discussing SUDEP with patients and all clinicians routinely discuss SUDEP with newly diagnosed epilepsy patients; The FAI has diffused into practice through meetings and discussions with colleagues; ‘Breaking Good News’ refers to the ambivalence clinicians feel about discussing SUDEP; ‘Falsely anticipating anxiety’ refers to clinicians anticipating a distressed response from patients despite this very rarely occurring; Clinicians suggest that ‘pressure hinders effective communication’ to patients – suggesting that the pressure to discuss SUDEP early after diagnosis may have an emotional impact on patients and affect the amount of information they can take in. Implications for guideline development are discussed

    The potential for vaccines against scour worms of small ruminants

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    This review addresses the research landscape regarding vaccines against scour worms, particularly Trichostrongylus spp. and Teladorsagia circumcincta. The inability of past research to deliver scour-worm vaccines with reliable and reproducible efficacy has been due in part to gaps in knowledge concerning: (i) host-parasite interactions leading to development of type-2 immunity, (ii) definition of an optimal suite of parasite antigens, and (iii) rational formulation and administration to induce protective immunity against gastrointestinal nematodes (GIN) at the site of infestation. Recent ‘omics’ developments enable more systematic analyses. GIN genomes are reaching completion, facilitating “reverse vaccinology” approaches that have been used successfully for the Rhipicephalus australis vaccine for cattle tick, while methods for gene silencing and editing in GIN enable identification and validation of potential vaccine antigens. We envisage that any efficacious scour worm vaccine(s) would be adopted similarly to “Barbervax™” within integrated parasite management schemes. Vaccines would therefore effectively parallel the use of resistant animals, and reduce the frequency of drenching and pasture contamination. These aspects of integration, efficacy and operation require updated models and validation in the field. The conclusion of this review outlines an approach to facilitate an integrated research program

    Successful immunization against a parasitic nematode by vaccination with recombinant proteins

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    AbstractInfection of humans and livestock with parasitic nematodes can have devastating effects on health and production, affecting food security in both developed and developing regions. Despite decades of research, the development of recombinant sub-unit vaccines against these pathogens has been largely unsuccessful. We have developed a strategy to identify protective antigens from Teladorsagia circumcincta, the major pathogen causing parasitic gastroenteritis in small ruminants in temperate regions, by studying IgA responses directed at proteins specific to post-infective larvae. Antigens were also selected on the basis of their potential immunomodulatory role at the host/parasite interface. Recombinant versions of eight molecules identified by immunoproteomics, homology with vaccine candidates in other nematodes and/or with potential immunoregulatory activities, were therefore administered to sheep in a single vaccine formulation. The vaccine was administered three times with Quil A adjuvant and the animals subsequently subjected to a repeated challenge infection designed to mimic field conditions. Levels of protection in the vaccinates were compared to those obtained in sheep administered with Quil A alone. The trial was performed on two occasions. In both trials, vaccinates had significantly lower mean fecal worm egg counts (FWECs) over the sampling period, with a mean reduction in egg output of 70% (Trial 1) and 58% (Trial 2). During the period of peak worm egg shedding, vaccinates shed 92% and 73% fewer eggs than did controls in Trials 1 and 2, respectively. At post mortem, vaccinates had 75% (Trial 1) and 56% (Trial 2) lower adult nematode burdens than the controls. These levels of protection are the highest observed in any system using a nematode recombinant sub-unit vaccine in the definitive ruminant host and indicate that control of parasitic helminths via vaccination with recombinant subunit vaccine cocktails is indeed an alternative option in the face of multi-drug resistance

    The effect of Psoroptes ovis infestation on ovine epidermal barrier function

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    Sheep scab is an intensively pruritic, exudative and allergic dermatitis of sheep caused by the ectoparasitic mite Psoroptes ovis. The purpose of the present study was to investigate the effect of P. ovis infestation on different components of the ovine epidermal barrier within the first 24 hours post-infestation (hpi). To achieve this, the expression of epidermal differentiation complex (EDC) genes and epidermal barrier proteins, the nature and severity of epidermal pathology and transepidermal water loss (TEWL) were evaluated. By 1 hpi a significant dermal polymorphonuclear infiltrate and a significant increase in TEWL with maximal mean TEWL (598.67 g/m(2)h) were observed. Epidermal pathology involving intra-epidermal pustulation, loss of epidermal architecture and damage to the basement membrane was seen by 3 hpi. Filaggrin and loricrin protein levels in the stratum corneum declined significantly in the first 24 hpi and qPCR validation confirmed the decrease in expression of the key EDC genes involucrin, filaggrin and loricrin observed by microarray analysis, with 5.8-fold, 4.5-fold and 80-fold decreases, respectively by 24 hpi. The present study has demonstrated that early P. ovis infestation disrupts the ovine epidermal barrier causing significant alterations in the expression of critical barrier components, epidermal pathology, and TEWL. Many of these features have also been documented in human and canine atopic dermatitis suggesting that sheep scab may provide a model for the elucidation of events occurring in the early phases of atopic sensitisation

    Development of bovine abomasal organoids as a novel in-vitro model to study host-parasite interactions in gastrointestinal nematode infections

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    Gastro-intestinal nematode (GIN) parasites are a major cause of production losses in grazing cattle, primarily through reduced growth rates in young animals. Control of these parasites relies heavily on anthelmintic drugs; however, with growing reports of resistance to currently available anthelmintics, alternative methods of control are required. A major hurdle in this work has been the lack of physiologically relevant in vitro infection models that has made studying precise interactions between the host and the GINs difficult. Such mechanistic insights into the infection process will be valuable for the development of novel targets for drugs, vaccines, or other interventions. Here we created bovine gastric epithelial organoids from abomasal gastric tissue and studied their application as in vitro models for understanding host invasion by GIN parasites. Transcriptomic analysis of gastric organoids across multiple passages and the corresponding abomasal tissue showed conserved expression of tissue-specific genes across samples, demonstrating that the organoids are representative of bovine gastric tissue from which they were derived. We also show that self-renewing and self-organising three-dimensional organoids can also be serially passaged, cryopreserved, and resuscitated. Using Ostertagia ostertagi, the most pathogenic gastric parasite in cattle in temperate regions, we show that cattle gastric organoids are biologically relevant models for studying GIN invasion in the bovine abomasum. Within 24 h of exposure, exsheathed larvae rapidly and repeatedly infiltrated the lumen of the organoids. Prior to invasion by the parasites, the abomasal organoids rapidly expanded, developing a ‘ballooning’ phenotype. Ballooning of the organoids could also be induced in response to exposure to parasite excretory/secretory products. In summary, we demonstrate the power of using abomasal organoids as a physiologically relevant in vitro model system to study interactions of O. ostertagi and other GIN with bovine gastrointestinal epithelium

    Revised valuation of flood regulation services of existing forest cover to inform natural capital accounts

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    This report provides updated evidence on the value of existing woodland in England, Scotland and Wales in regulating flood flows and reducing flood risk in downstream communities. This is a ground-breaking area of analysis that is attempting to improve on what was previously a significant evidence gap in the economic value of woodland. The study updates a previous evaluation (Broadmeadow et al., 2018) with improved estimates for the volume of flood water potentially removed by woodland or retained by its hydraulic roughness. The impacts of woodlands are compared with two alternative land uses, short grass and bare soil. The scope of the analysis was also extended to include the contribution of conifer woodlands, small woodlands, and trees outside of woodlands. A companion report (Fitch et al., 2022) is available that applies the approach to other natural capital types, including woodland, although values are not directly comparable due to methodological differences

    Occurrence of Salmonella-Specific Bacteriophages in Swine Feces Collected from Commercial Farms

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    Salmonella is one of the leading causes of human foodborne illness and is associated with swine production. Bacteriophages are naturally occurring viruses that prey on bacteria and have been suggested as a potential intervention strategy to reduce Salmonella levels in food animals on the farm and in the lairage period. If phages are to be used to improve food safety, then we must understand the incidence and natural ecology of both phages and their hosts in the intestinal environment. This study investigates the incidence of phages that are active against Salmonella spp. in the feces of commercial finishing swine. Fecal samples (n = 60) were collected from each of 10 commercial swine finishing operations. Samples were collected from 10 randomly selected pens throughout each operation; a total of 600 fecal samples were collected. Salmonella spp. were found in 7.3% (44/600) of the fecal samples. Bacteriophages were isolated from fecal samples through two parallel methods: (1) initial enrichment in Salmonella Typhimurium; (2) initial enrichment in Escherichia coli B (an indicator strain), followed by direct spot testing against Salmonella Typhimurium. Bacteriophages active against Salmonella Typhimurium were isolated from 1% (6/600) of the individual fecal samples when initially enriched in Salmonella Typhimurium, but E. coli B-killing phages were isolated from 48.3% (290/600) of the fecal samples and only two of these phages infected Salmonella Typhimurium on secondary plating. Collectively, our results indicate that bacteriophages are widespread in commercial swine, but those capable of killing Salmonella Typhimurium may be present at relatively low population levels. These results indicate that phages (predator) populations may vary along with Salmonella (prey) populations; and that phages could potentially be used as a food safety pathogen reduction strategy in swine
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