The Sight Loss and Vision Priority Setting Partnership (SLV-PSP): overview and results of the research prioritisation survey process

Objectives: The Sight Loss and Vision Priority Setting Partnership aimed to identify research priorities relating to sight loss and vision through consultation with patients, carers and clinicians. These priorities can be used to inform funding bodies’ decisions and enhance the case for additional research funding. Design: Prospective survey with support from the James Lind Alliance. Setting: UK-wide National Health Service (NHS) and non-NHS. Participants: Patients, carers and eye health professionals. Academic researchers were excluded solely from the prioritisation process. The survey was disseminated by patient groups, professional bodies, at conferences and through the media, and was available for completion online, by phone, by post and by alternative formats (Braille and audio). Outcome measure: People were asked to submit the questions about prevention, diagnosis and treatment of sight loss and eye conditions that they most wanted to see answered by research. Returned survey questions were reviewed by a data assessment group. Priorities were established across eye disease categories at final workshops. Results: 2220 people responded generating 4461 submissions. Sixty-five per cent of respondents had sight loss and/or an eye condition. Following initial data analysis, 686 submissions remained which were circulated for interim prioritisation (excluding cataract and ocular cancer questions) to 446 patients/carers and 218 professionals. The remaining 346 questions were discussed at final prioritisation workshops to reach agreement of top questions per category. Conclusions: The exercise engaged a diverse community of stakeholders generating a wide range of conditions and research questions. Top priority questions were established across 12 eye disease categories. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial

Neutrophil Extracellular Traps Go Viral

Neutrophils are the most numerous immune cells. Their importance as the first line of defense against bacterial and fungal pathogens is well described. In contrast, the role of neutrophils in controlling viral infections is less clear. Bacterial and fungal pathogens can stimulate neutrophils extracellular traps (NETs) in a process called NETosis. Although NETosis has previously been described as a special form of programmed cell death, there are forms of NET production that do not end with the demise of neutrophils. As an end result of NETosis, genomic DNA complexed with microbicidal proteins is expelled from neutrophils. These structures can kill pathogens or at least prevent their local spread within host tissue. On the other hand, disproportionate NET formation can cause local or systemic damage. Only recently, it was recognized that viruses can also induce NETosis. In this review, we discuss the mechanisms by which NETs are produced in the context of viral infection and how this may contribute to both antiviral immunity and immunopathology. Finally, we shed light on viral immune evasion mechanisms targeting NETs

The in vivo efficacy of two administration routes of a phage cocktail to reduce numbers of Campylobacter coli and Campylobacter jejuni in chickens

<p>Abstract</p> <p>Background</p> <p>Poultry meat is one of the most important sources of human campylobacteriosis, an acute bacterial enteritis which is a major problem worldwide. <it>Campylobacter </it><it>coli </it>and <it>Campylobacter </it><it>jejuni </it>are the most common <it>Campylobacter </it>species associated with this disease. These pathogens live in the intestinal tract of most avian species and under commercial conditions they spread rapidly to infect a high proportion of the flock, which makes their treatment and prevention very difficult. Bacteriophages (phages) are naturally occurring predators of bacteria with high specificity and also the capacity to evolve to overcome bacterial resistance. Therefore phage therapy is a promising alternative to antibiotics in animal production. This study tested the efficacy of a phage cocktail composed of three phages for the control of poultry infected with <it>C. coli </it>and <it>C. jejuni</it>. Moreover, it evaluated the effectiveness of two routes of phage administration (by oral gavage and in feed) in order to provide additional information regarding their future use in a poultry unit.</p> <p>Results</p> <p>The results indicate that experimental colonisation of chicks was successful and that the birds showed no signs of disease even at the highest dose of <it>Campylobacter </it>administered. The phage cocktail was able to reduce the titre of both <it>C. coli </it>and <it>C. jejuni </it>in faeces by approximately 2 log₁₀cfu/g when administered by oral gavage and in feed. This reduction persisted throughout the experimental period and neither pathogen regained their former numbers. The reduction in <it>Campylobacter </it>titre was achieved earlier (2 days post-phage administration) when the phage cocktail was incorporated in the birds' feed. <it>Campylobacter </it>strains resistant to phage infection were recovered from phage-treated chickens at a frequency of 13%. These resistant phenotypes did not exhibit a reduced ability to colonize the chicken guts and did not revert to sensitive types.</p> <p>Conclusions</p> <p>Our findings provide further evidence of the efficacy of phage therapy for the control of <it>Campylobacter </it>in poultry. The broad host range of the novel phage cocktail enabled it to target both <it>C. jejuni </it>and <it>C. coli </it>strains. Moreover the reduction of <it>Campylobacter </it>by approximately 2 log₁₀cfu/g, as occurred in our study, could lead to a 30-fold reduction in the incidence of campylobacteriosis associated with consumption of chicken meals (according to mathematical models). To our knowledge this is the first report of phage being administered in feed to <it>Campylobacter-</it>infected chicks and our results show that it lead to an earlier and more sustainable reduction of <it>Campylobacter </it>than administration by oral gavage. Therefore the present study is of extreme importance as it has shown that administering phages to poultry via the food could be successful on a commercial scale.</p

Percutaneous Transhepatic Release of an Impacted Lithotripter Basket and Its Fractured Traction Wire Using a Goose-Neck Snare: a Case Report

In a patient with a distal common bile duct stone, a fracture of the traction wire of the basket occurring during the performance of mechanical lithotripsy resulted in the impaction of the lithotripter basket with a stone. The impacted lithotripter basket combined with a fracture of the traction wire is a rare complication of endoscopic stone removal. We were able to pull the impacted basket using an Amplatz goose-neck snare inserted via the percutaneous transhepatic route, which resulted in the freeing of the entrapped stone into the dilated supra-ampullary bile duct. The fractured traction wire and basket could be safely removed by pulling the traction wire from the mouth. The present report is the first to describe the safe and effective use of an Amplatz goose-neck snare for the management of a lithotripter basket impacted with a stone and a fractured traction wire

Respiratory Syncytial Virus Binds and Undergoes Transcription in Neutrophils From the Blood and Airways of Infants With Severe Bronchiolitis

Background. Neutrophils are the predominant cell in the lung inflammatory infiltrate of infants with respiratory syncytial virus (RSV) bronchiolitis. Although it has previously been shown that neutrophils from both blood and bronchoalveolar lavage (BAL) are activated, little is understood about their role in response to RSV infection. This study investigated whether RSV proteins and mRNA are present in neutrophils from blood and BAL of infected infants

The in vivo efficacy of two administration routes of a phage cocktail to reduce numbers of Campylobacter coli and Campylobacter jejuni in chickens

Background Poultry meat is one of the most important sources of human campylobacteriosis, an acute bacterial enteritis which is a major problem worldwide. Campylobacter coli and Campylobacter jejuni are the most common Campylobacter species associated with this disease. These pathogens live in the intestinal tract of most avian species and under commercial conditions they spread rapidly to infect a high proportion of the flock, which makes their treatment and prevention very difficult. Bacteriophages (phages) are naturally occurring predators of bacteria with high specificity and also the capacity to evolve to overcome bacterial resistance. Therefore phage therapy is a promising alternative to antibiotics in animal production. This study tested the efficacy of a phage cocktail composed of three phages for the control of poultry infected with C. coli and C. jejuni. Moreover, it evaluated the effectiveness of two routes of phage administration (by oral gavage and in feed) in order to provide additional information regarding their future use in a poultry unit. Results The results indicate that experimental colonisation of chicks was successful and that the birds showed no signs of disease even at the highest dose of Campylobacter administered. The phage cocktail was able to reduce the titre of both C. coli and C. jejuni in faeces by approximately 2 log10 cfu/g when administered by oral gavage and in feed. This reduction persisted throughout the experimental period and neither pathogen regained their former numbers. The reduction in Campylobacter titre was achieved earlier (2 days post-phage administration) when the phage cocktail was incorporated in the birds' feed. Campylobacter strains resistant to phage infection were recovered from phage-treated chickens at a frequency of 13%. These resistant phenotypes did not exhibit a reduced ability to colonize the chicken guts and did not revert to sensitive types. Conclusions Our findings provide further evidence of the efficacy of phage therapy for the control of Campylobacter in poultry. The broad host range of the novel phage cocktail enabled it to target both C. jejuni and C. coli strains. Moreover the reduction of Campylobacter by approximately 2 log10cfu/g, as occurred in our study, could lead to a 30-fold reduction in the incidence of campylobacteriosis associated with consumption of chicken meals (according to mathematical models). To our knowledge this is the first report of phage being administered in feed to Campylobacter- infected chicks and our results show that it lead to an earlier and more sustainable reduction of Campylobacter than administration by oral gavage. Therefore the present study is of extreme importance as it has shown that administering phages to poultry via the food could be successful on a commercial scale.The authors acknowledge the European Commission under the FP-6-2003- Food-2-A to the project 2005-7224 for the financial support and the Portuguese Foundation for Science and Technology (FCT) through the grant SFRH/BD/23484/2005