Enhanced avidity from a multivalent fluorescent antimicrobial peptide enables pathogen detection in a human lung model.

Rapid in situ detection of pathogens coupled with high resolution imaging in the distal human lung has the potential to provide new insights and diagnostic utility in patients in whom pneumonia is suspected. We have previously described an antimicrobial peptide (AMP) Ubiquicidin (fragment UBI) labelled with an environmentally sensitive fluorophore that optically detected bacteria in vitro but not ex vivo. Here, we describe further chemical development of this compound and demonstrate that altering the secondary structure of the AMP to generate a tri-branched dendrimeric scaffold provides enhanced signal in vitro and ex vivo and consequently allows the rapid detection of pathogens in situ in an explanted human lung.

In situ identification of Gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid A.

Respiratory infections in mechanically ventilated patients caused by Gram-negative bacteria are a major cause of morbidity. Rapid and unequivocal determination of the presence, localization, and abundance of bacteria is critical for positive resolution of the infections and could be used for patient stratification and for monitoring treatment efficacy. Here, we developed an in situ approach to visualize Gram-negative bacterial species and cellular infiltrates in distal human lungs in real time.

Nebulisation of synthetic lamellar lipids mitigates radiation-induced lung injury in a large animal model.

Methods to protect against radiation-induced lung injury (RILI) will facilitate the development of more effective radio-therapeutic protocols for lung cancer and may provide the means to protect the wider population in the event of a deliberate or accidental nuclear or radiological event. We hypothesised that supplementing lipid membranes through nebulization of synthetic lamellar lipids would mitigate RILI. Following pre-treatment with either nebulised lamellar lipids or saline, anaesthetised sheep were prescribed fractionated radiotherapy (30 Gray (Gy) total dose in five 6 Gy fractions at 3-4 days intervals) to a defined unilateral lung volume.

Post-mortem magnetic resonance imaging in patients with suspected prion disease: Pathological confirmation, sensitivity, specificity and observer reliability. A national registry.

The relationship between magnetic resonance imaging (MRI) and clinical variables in patients suspected to have Creutzfeldt-Jakob Disease (CJD) is uncertain. We aimed to determine which MRI features of CJD (positive or negative), previously described in vivo, accurately identify CJD, are most reliably detected, vary with disease duration, and whether combined clinical and imaging features increase diagnostic accuracy for CJD. Prospective patients suspected of having CJD were referred to the National CJD Research and Surveillance Unit between 1994-2004; post-mortem, brains were sent for MRI and histopathology.

Comparing microbiotas in the upper aerodigestive and lower respiratory tracts of lambs.

Background: Recently, the importance of the lung microbiota during health and disease has been examined in humans and in small animal models. Whilst sheep have been proposed as an appropriate large animal model for studying the pathophysiology of a number of important human respiratory diseases, it is clearly important to continually define the limits of agreement between these systems as new concepts emerge. In humans, it has recently been established that the lung microbiota is seeded by microbes from the oral cavity.

Microbiota in Exhaled Breath Condensate and the Lung.

The lung microbiota is commonly sampled using relatively invasive bronchoscopic procedures. Exhaled breath condensate (EBC) collection potentially offers a less invasive alternative for lung microbiota sampling. We compared lung microbiota samples retrieved by protected specimen brushings (PSB) and exhaled breath condensate collection.

Opioid, NSAID, and OTC Analgesic Medications for Dental Procedures: PEARL Network Findings.

Objective: Dental treatment is often categorized as a moderately or severely painful experience; however, no clinical data reported by the patient and dentist currently exists to support this degree of pain. This has contributed possibly to the overprescribing of analgesics, in particular the opioid class of medications. The primary objective of the study was to document the dentists' postprocedural prescriptions and recommendations for analgesic medications and their effectiveness for a 5-day period.

Variability of the Sheep Lung Microbiota.

Unlabelled: Sequencing technologies have recently facilitated the characterization of bacterial communities present in lungs during health and disease. However, there is currently a dearth of information concerning the variability of such data in health both between and within subjects. This study seeks to examine such variability using healthy adult sheep as our model system.

Structural Development, Cellular Differentiation and Proliferation of the Respiratory Epithelium in the Bovine Fetal Lung.

Fetal bovine lung samples of 11 different gestational ages were assigned to a classical developmental stage based on histological morphology. Immunohistochemistry was used to characterize the morphology of forming airways, proliferation rate of airway epithelium and the presence of epithelial cell types (i.e.

Lung Microbiota Changes Associated with Chronic Pseudomonas aeruginosa Lung Infection and the Impact of Intravenous Colistimethate Sodium.

Background: Exacerbations associated with chronic lung infection with Pseudomonas aeruginosa are a major contributor to morbidity, mortality and premature death in cystic fibrosis. Such exacerbations are treated with antibiotics, which generally lead to an improvement in lung function and reduced sputum P. aeruginosa density.

Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial.

Background: Lung delivery of plasmid DNA encoding the CFTR gene complexed with a cationic liposome is a potential treatment option for patients with cystic fibrosis. We aimed to assess the efficacy of non-viral CFTR gene therapy in patients with cystic fibrosis.

Methods: We did this randomised, double-blind, placebo-controlled, phase 2b trial in two cystic fibrosis centres with patients recruited from 18 sites in the UK.

Prevalence of persistent pain 3 to 5 years post primary root canal therapy and its impact on oral health-related quality of life: PEARL Network findings.

Introduction: The frequency of persistent pain 3-5 years after primary root canal therapy and its impact on the patient's perceived oral health-related quality of life was determined in a practice-based research network.

Methods: All patients presenting to participating network practices who received primary root canal therapy and restoration for a permanent tooth 3-5 years previously were invited to enroll. Persistent pain was defined as pain occurring spontaneously or elicited by percussion, palpation, or biting.

Sheep lung segmental delivery strategy demonstrates adenovirus priming of local lung responses to bacterial LPS and the role of elafin as a response modulator.

Viral lung infections increase susceptibility to subsequent bacterial infection. We questioned whether local lung administration of recombinant adenoviral vectors in the sheep would alter the susceptibility of the lung to subsequent challenge with bacterial lipopolysaccharide (LPS). We further questioned whether local lung expression of elafin, a locally produced alarm anti-LPS/anti-bacterial molecule, would modulate the challenge response.

Outcomes of implants and restorations placed in general dental practices: a retrospective study by the Practitioners Engaged in Applied Research and Learning (PEARL) Network.

Objectives: The authors conducted a study to determine the types, outcomes, risk factors and esthetic assessment of implants and their restorations placed in the general practices of a practice-based research network.

Methods: All patients who visited network practices three to five years previously and underwent placement of an implant and restoration within the practice were invited to enroll. Practitioner-investigators (P-Is) recorded the status of the implant and restoration, characteristics of the implant site and restoration, presence of peri-implant pathology and an esthetic assessment by the P-I and patient.

The safety profile of a cationic lipid-mediated cystic fibrosis gene transfer agent following repeated monthly aerosol administration to sheep.

Clinically effective gene therapy for Cystic Fibrosis has been a goal for over 20 years. A plasmid vector (pGM169) that generates persistent expression and reduced host inflammatory responses in mice has raised prospects for translation to the clinic. The UK CF Gene Therapy Consortium is currently evaluating long-term repeated delivery of pGM169 complexed with the cationic lipid GL67A in a large Multidose Trial.

A lung segmental model of chronic Pseudomonas infection in sheep.

Background: Chronic lung infection with Pseudomonas aeruginosa is a major contributor to morbidity, mortality and premature death in cystic fibrosis. A new paradigm for managing such infections is needed, as are relevant and translatable animal models to identify and test concepts. We sought to improve on limitations associated with existing models of infection in small animals through developing a lung segmental model of chronic Pseudomonas infection in sheep.

An assessment of the perceived benefits and challenges of participating in a practice-based research network.

Background: A survey was conducted to describe the benefits of and challenges to practitioner participation in the Practitioners Engaged in Applied Research and Learning (PEARL) Network, a dental practice-based research network (PBRN). The results were compared with results from medical PBRNs across different tiers of participation (based on practitioner-investigators previous involvement with PEARL research protocols).

Methods: A 39-item web-based survey addressed the benefits of PBRN participation on three levels: individual/practitioner, practice (office), and community/professional.

Treatments for hypersensitive noncarious cervical lesions: a Practitioners Engaged in Applied Research and Learning (PEARL) Network randomized clinical effectiveness study.

Background: The Practitioners Engaged in Applied Research and Learning (PEARL) Network conducted a three-armed randomized clinical study to determine the comparative effectiveness of three treatments for hypersensitive noncarious cervical lesions (NCCLs): use of a potassium nitrate dentifrice for treatment of hypersensitivity, placement of a resin-based composite restoration and placement of a sealant.

Methods: Seventeen trained practitioner-investigators (P-Is) in the PEARL Network enrolled participants (N = 304) with hypersensitive posterior NCCLs who met enrollment criteria. Participants were assigned to treatments randomly.

Gene expression changes associated with the airway wall response to injury.

Background: Understanding the way in which the airway heals in response to injury is fundamental to dissecting the mechanisms underlying airway disease pathology. As only limited data is available in relation to the in vivo characterisation of the molecular features of repair in the airway we sought to characterise the dynamic changes in gene expression that are associated with the early response to physical injury in the airway wall.

Methodology/principal Findings: We profiled gene expression changes in the airway wall using a large animal model of physical injury comprising bronchial brush biopsy in anaesthetised sheep.

BrdU pulse labelling in vivo to characterise cell proliferation during regeneration and repair following injury to the airway wall in sheep.

The response of S-phase cells labelled with bromodeoxyuridine (BrdU) in sheep airways undergoing repair in response to endobronchial brush biopsy was investigated in this study. Separate sites within the airway tree of anaesthetised sheep were biopsied at intervals prior to pulse labelling with BrdU, which was administered one hour prior to euthanasia. Both brushed and spatially disparate unbrushed (control) sites were carefully mapped, dissected, and processed to facilitate histological analysis of BrdU labelling.

Dental hygienists' role in practice based research: PEARL Network evaluation.

Purpose: The goal of this paper is to evaluate the PEARL Network's satisfaction with training/support and assess the relationship between practice research coordinators (PRCs) involvement and study participation.

Methods: At the PEARL Network 2011 Annual Meeting, an evaluation form was completed by practitioner-investigators and PRCs who attended the annual meeting. Results from the paper evaluation form were entered into an Excel database, and analyzed using the statistical analysis software SPSS.