Host genotype affects endotoxin release in excreta of broilers at slaughter age

Host genotype, early post-hatch feeding, and pre- and probiotics are factors known to modulate the gut microbiome. However, there is a knowledge gap on the effect of both chicken genotype and these dietary strategies and their interplay on fecal microbiome composition and diversity, which, in turn, can affect the release of endotoxins in the excreta of broilers. Endotoxins are a major concern as they can be harmful to both animal and human health. The main goal of the current study was to investigate whether it was possible to modulate the fecal microbiome, thereby reducing endotoxin concentrations in the excreta of broiler chickens. An experiment was carried out with a 2 × 2 × 2 factorial arrangement including the following three factors: 1) genetic strain (fast-growing Ross 308 vs. slower growing Hubbard JA757); 2) no vs. combined use of probiotics and prebiotics in the diet and drinking water; and 3) early feeding at the hatchery vs. non-early feeding. A total of 624 Ross 308 and 624 Hubbard JA757 day-old male broiler chickens were included until d 37 and d 51 of age, respectively. Broilers ( N = 26 chicks/pen) were housed in a total of 48 pens, and there were six replicate pens/treatment groups. Pooled cloacal swabs ( N = 10 chickens/pen) for microbiome and endotoxin analyses were collected at a target body weight (BW) of 200 g, 1 kg, and 2.5 kg. Endotoxin concentration significantly increased with age ( p = 0.01). At a target BW of 2.5 kg, Ross 308 chickens produced a considerably higher amount of endotoxins ( Δ = 552.5 EU/mL) than the Hubbard JA757 chickens ( p < 0.01). A significant difference in the Shannon index was observed for the interaction between the use of prebiotics and probiotics, and host genotype ( p = 0.02), where Ross 308 chickens with pre-/probiotics had lower diversity than Hubbard JA757 chickens with pre-/probiotics. Early feeding did not affect both the fecal microbiome and endotoxin release. Overall, the results suggest that the chicken genetic strain may be an important factor to take into account regarding fecal endotoxin release, although this needs to be further investigated under commercial conditions

Healthcare practice placements: back to the drawing board?

YesBackground: Sourcing healthcare practice placements continues to present a challenge for higher education institutions. Equally, the provision of clinical placements by healthcare providers is not at the forefront of their agenda. In view of this, the historic and traditional models of clinical placements is becoming more difficult to provide. In light of this, new models of clinical placements are being explored. Aims: This literature review explores the differing models of clinical placements in use and examines the merits and limitation of each. Methods: A mixed-methods literature review with a pragmatic approach has been used. Findings: Several placement models were described, including the traditional 1:1 model as well as 2:1, 3:1. The hub and spoke, capacity development facilitator, collaborative learning in practice and role emerging placement models were also discussed. Conclusion: There is a considerable paucity of high-quality evidence evaluating differing placement modules. Further research is required to evaluate the differing placement models from a students, clinical educators and service user’s perspective

Cellular senescence impairs the reversibility of pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) in congenital cardiac shunts can be reversed by hemodynamic unloading (HU) through shunt closure. However, this reversibility potential is lost beyond a certain point in time. The reason why PAH becomes irreversible is unknown. In this study, we used MCT+shunt-induced PAH in rats to identify a dichotomous reversibility response to HU, similar to the human situation. We compared vascular profiles of reversible and irreversible PAH using RNA sequencing. Cumulatively, we report that loss of reversibility is associated with a switch from a proliferative to a senescent vascular phenotype and confirmed markers of senescence in human PAH-CHD tissue. In vitro, we showed that human pulmonary endothelial cells of patients with PAH are more vulnerable to senescence than controls in response to shear stress and confirmed that the senolytic ABT263 induces apoptosis in senescent, but not in normal, endothelial cells. To support the concept that vascular cell senescence is causal to the irreversible nature of end-stage PAH, we targeted senescence using ABT263 and induced reversal of the hemodynamic and structural changes associated with severe PAH refractory to HU. The factors that drive the transition from a reversible to irreversible pulmonary vascular phenotype could also explain the irreversible nature of other PAH etiologies and provide new leads for pharmacological reversal of end-stage PAH

Comparing the transmission of carbapenemase-producing and extended-spectrum beta-lactamase-producing Escherichia coli between broiler chickens

The emergence of carbapenemase-producing Enterobacteriaceae (CPE) is a threat to public health, because of their resistance to clinically important carbapenem antibiotics. The emergence of CPE in meat-producing animals is particularly worrying because consumption of meat contaminated with resistant bacteria comparable to CPE, such as extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, contributed to colonization in humans worldwide. Currently, no data on the transmission of CPE in livestock is available. We performed a transmission experiment to quantify the transmission of CPE between broilers to fill this knowledge gap and to compare the transmission rates of CPE and other antibiotic-resistant E. coli. A total of 180 Ross 308 broiler chickens were distributed over 12 pens on the day of hatch (day 0). On day 5, half of the 10 remaining chickens in each pen were orally inoculated with 5·10 2 colony-forming units of CPE, ESBL, or chloramphenicol-resistant E. coli (catA1). To evaluate the effect of antibiotic treatment, amoxicillin was given twice daily in drinking water in 6 of the 12 pens from days 2-6. Cloacal swabs of all animals were taken to determine the number of infectious broilers. We used a Bayesian hierarchical model to quantify the transmission of the E. coli strains. E. coli can survive in the environment and serve as a reservoir. Therefore, the susceptible-infectious transmission model was adapted to account for the transmission of resistant bacteria from the environment. In addition, the caecal microbiome was analyzed on day 5 and at the end of the experiment on day 14 to assess the relationship between the caecal microbiome and the transmission rates. The transmission rates of CPE were 52 - 68 per cent lower compared to ESBL and catA1, but it is not clear if these differences were caused by differences between the resistance genes or by other differences between the E. coli strains. Differences between the groups in transmission rates and microbiome diversity did not correspond to each other, indicating that differences in transmission rates were probably not caused by major differences in the community structure in the caecal microbiome. Amoxicillin treatment from day 2-6 increased the transmission rate more than three-fold in all inoculums. It also increased alpha-diversity compared to untreated animals on day 5, but not on day 14, suggesting only a temporary effect. Future research could incorporate more complex transmission models with different species of resistant bacteria into the Bayesian hierarchical model

The Genome of Winter Moth (Operophtera brumata) Provides a Genomic Perspective on Sexual Dimorphism and Phenology

The winter moth (Operophtera brumata) belongs to one of the most species-rich families in Lepidoptera, the Geometridae (approximately 23,000 species). This family is of great economic importance as most species are herbivorous and capable of defoliating trees. Genome assembly of the winter moth allows the study of genes and gene families, such as the cytochrome P450 gene family, which is known to be vital in plant secondary metabolite detoxification and host-plant selection. It also enables exploration of the genomic basis for female brachyptery (wing reduction), a feature of sexual dimorphism in winter moth, and for seasonal timing, a trait extensively studied in this species. Here we present a reference genome for the winter moth, the first geometrid and largest sequenced Lepidopteran genome to date (638 Mb) including a set of 16,912 predicted protein-coding genes. This allowed us to assess the dynamics of evolution on a genome-wide scale using the P450 gene family. We also identified an expanded gene family potentially linked to female brachyptery, and annotated the genes involved in the circadian clock mechanism as main candidates for involvement in seasonal timing. The genome will contribute to Lepidopteran genomic resources and comparative genomics. In addition, the genome enhances our ability to understand the genetic and molecular basis of insect seasonal timing and thereby provides a reference for future evolutionary and population studies on the winter moth

Comparing the transmission of carbapenemase-producing and extended-spectrum beta-lactamase-producingEscherichia colibetween broiler chickens

Abstract The emergence of carbapenemase-producing Enterobacteriaceae (CPE) is a threat to public health, because of their resistance to clinically important carbapenem antibiotics. The emergence of CPE in meat-producing animals is particularly worrying because consumption of meat contaminated with resistant bacteria similar to CPE, such as extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, contributed to colonization in humans worldwide. Currently, no data on the transmission of CPE in livestock is available. We performed a transmission experiment to quantify the transmission of CPE between broilers to fill this knowledge gap and to compare the transmission rates of CPE and other antibiotic-resistant E. coli. A total of 180 Ross 308 broiler chickens were distributed on the day of hatch (day 0) over 12 pens. On day 5, half of the chickens in each pen were orally inoculated with 5·102 colony-forming units of CPE, ESBL, or chloramphenicol-resistant E. coli (catA1). Amoxicillin drinking water treatment was given twice daily in 6 of the 12 pens from days 2 to 6 to evaluate the effect of antibiotic treatment on the transmission rates. Cloacal swabs of all animals were taken to determine the number of infectious broilers. We used a Bayesian hierarchical model to quantify the transmission of the E. coli strains. E. coli can survive in the environment and serve as a reservoir. Therefore, the susceptible-infectious transmission model was adapted to account for the transmission of resistant bacteria from the environment. In addition, the caecal microbiome was analyzed on day 5 and at the end of the experiment on day 14 to assess the relationship between the caecal microbiome and the transmission rates. The transmission rates of CPE were 52 – 68 per cent lower compared to ESBL and catA1, but it is not clear if these differences were caused by differences between the resistance genes or between the E. coli strains. Differences between the groups in transmission rates and microbiome diversity did not correspond to each other, indicating that differences in transmission rates were probably not caused by major differences in the community structure in the caecal microbiome. Amoxicillin treatment from day 2 to 6 increased the transmission rate more than three-fold in all inoculums. It also increased alpha-diversity compared to untreated animals on day 5, but not on day 14, suggesting only a temporary effect. Future research could incorporate more complex transmission models with different species of resistant bacteria into the Bayesian hierarchical model

Effective Gene Therapy in a Mouse Model of Prion Diseases

Classical drug therapies against prion diseases have encountered serious difficulties. It has become urgent to develop radically different therapeutic strategies. Previously, we showed that VSV-G pseudotyped FIV derived vectors carrying dominant negative mutants of the PrP gene are efficient to inhibit prion replication in chronically prion-infected cells. Besides, they can transduce neurons and cells of the lymphoreticular system, highlighting their potential use in gene therapy approaches. Here, we used lentiviral gene transfer to deliver PrPQ167R virions possessing anti-prion properties to analyse their efficiency in vivo. Since treatment for prion diseases is initiated belatedly in human patients, we focused on the development of a curative therapeutic protocol targeting the late stage of the disease, either at 35 or 105 days post-infection (d.p.i.) with prions. We observed a prolongation in the lifespan of the treated mice that prompted us to develop a system of cannula implantation into the brain of prion-infected mice. Chronic injections of PrPQ167R virions were done at 80 and 95 d.p.i. After only two injections, survival of the treated mice was extended by 30 days (20%), accompanied by substantial improvement in behaviour. This delay was correlated with: (i) a strong reduction of spongiosis in the ipsilateral side of the brain by comparison with the contralateral side; and (ii) a remarkable decrease in astrocytic gliosis in the whole brain. These results suggest that chronic injections of dominant negative lentiviral vectors into the brain, may be a promising approach for a curative treatment of prion diseases

Developing health science students into integrated health professionals: a practical tool for learning

BACKGROUND:An integrated sense of professionalism enables health professionals to draw on relevant knowledge in context and to apply a set of professional responsibilities and ethical principles in the midst of changing work environments 12. Inculcating professionalism is therefore a critical goal of health professional education. Two multi-professional courses for first year Health Science students at the University of Cape Town, South Africa aim to lay the foundation for becoming an integrated health professional 3. In these courses a diagram depicting the domains of the integrated health professional is used to focus the content of small group experiential exercises towards an appreciation of professionalism. The diagram serves as an organising framework for conceptualising an emerging professional identity and for directing learning towards the domains of 'self as professional' 45.OBJECTIVE:This paper describes how a diagrammatic representation of the core elements of an integrated health professional is used as a template for framing course content and for organising student learning. Based on the assumption that all health care professionals should be knowledgeable, empathic and reflective, the diagram provides students and educators with a visual tool for investigating the subjective and objective dimensions of professionalism. The use of the diagram as an integrating point of reference for individual and small group learning is described and substantiated with relevant literature. CONCLUSION: The authors have applied the diagram with positive impact for the past six years with students and educators reporting that "it just makes sense". The article includes plans for formal evaluation. Evaluation to date is based on preliminary, informal feedback on the value of the diagram as a tool for capturing the domains of professionalism at an early stage in the undergraduate education of health professional students