Efficacy of a Topical Formulation Containing Emodepside and Praziquantel (Profender®, Bayer) against Nematodes in Captive Tortoises

Gastrointestinal parasites are commonly diagnosed in captive tortoises. In response, fenbendazole has traditionally been used as an anthelmintic, either in single or repeated doses. However, fenbendazole requires oral administration and the process can be very challenging in some individuals. A topical preparation containing emodepside and praziquantel (Profender®, Bayer, Leverkusen, Germany) is promoted as effective against a broad range of nematodes, trematodes, and cestodes. Although this product is currently only licensed for administration to cats, previous studies have shown positive results with tortoises. The aim of this study was to determine the efficacy of Profender against oxyurid and ascarid parasites in captive tortoises. This was achieved by quantifying nematode eggs per gram (EPG) in feces using a modified McMaster technique before (Day 0) and after (Days 14 and 33) topical application of Profender at a dose rate of 21.5 mg emodepside and 85.5 mg praziquantel per kilogram. Twenty-nine tortoises, representing four different species, were enrolled in this study of which 14 (48%; including Testudo hermanni and Testudo graeca) were positive for intestinal nematodes. Following treatment, the oxyurid EPG was slightly increased on Day 14 but declined significantly by Day 33 (59.7% reduction; P = 0.01), indicating a slow onset of effect and moderate efficacy 33 days posttreatment; however, no conclusions regarding efficacy against ascarids can be drawn from this study. Topical application of emodepside and praziquantel was well tolerated in our tortoise population and, therefore, could be considered as a useful alternative anthelmintic treatment protocol for captive tortoises

Involving people with diabetes and the wider community in diabetes research: a realist review protocol.

BACKGROUND: Patient and public involvement in diabetes research is now actively encouraged in different countries because it is believed that involving people with experience of the condition will improve the quality and relevance of the research. However, reviews of patient involvement have noted that inadequate resources, patients' and communities' lack of research knowledge, and researchers' lack of skills to involve patients and communities in research may present significant contextual barriers. Little is known about the extent of patient/community involvement in designing or delivering interventions for people with diabetes. A realist review of involvement will contribute to assessing when, how and why involvement works, or does not work, to produce better diabetes interventions. METHODS/DESIGN: This protocol outlines the process for conducting a realist review to map how patients and the public have been involved in diabetes research to date. The review questions ask the following: How have people with diabetes and the wider community been involved in diabetes research? What are the characteristics of the process that appear to explain the relative success or failure of involvement? How has involvement (or lack of involvement) in diabetes research influenced the development and conduct of diabetes research? The degree of support in the surrounding context will be assessed alongside the ways in which people interact in different settings to identify patterns of interaction between context, mechanisms and outcomes in different research projects. The level and extent of the involvement will be described for each stage of the research project. The descriptions will be critically reviewed by the people with diabetes on our review team. In addition, researchers and patients in diabetes research will be asked to comment. Information from researcher-patient experiences and documents will be compared to theories of involvement across a range of disciplines to create a mid-range theory describing how involvement (or lack of involvement) in diabetes research influences the development and conduct of diabetes research

Acyl Homoserine Lactones from Culture Supernatants of Pseudomonas aeruginosa Accelerate Host Immunomodulation

The virulence of Pseudomonas aeruginosa is multifactorial and under the control of quorum sensing signals, such as acyl homoserine lactones (AHLs). The importance of these molecules in the establishment of infection has been previously reported. These molecules either improve the virulence potential of P. aeruginosa or modulate the host immune response. To establish the immune modulating potential of quorum sensing signal molecules, previous studies have only used synthetic AHLs. However, there can be differences in the biological properties of synthetic and natural AHLs. The use of naturally extracted AHLs from the culture supernatant of P. aeruginosa is likely to simulate natural conditions more than the use of synthetic AHLs. Therefore, in the present study, the immune modulating potential of synthetic and naturally extracted AHLs was compared using a thymidine uptake assay, immunophenotyping and sandwich ELISA in order to assess mouse T-cell proliferation and production of Th1 and Th2 cytokines. Natural AHLs were able to suppress T-cell proliferation, even at low concentrations, compared to synthetic AHLs. The majority of cells undergoing proliferation were CD4+, as revealed by immunophenotyping. The inhibition of T-cells was stronger with natural AHLs compared to synthetic AHLs. Moreover, the natural AHLs were also able to shift immune responses away from host protective Th1 responses to pathogen protective Th2 responses

Nonrandom Distribution of Vector Ticks (Dermacentor variabilis) Infected by Francisella tularensis

The island of Martha's Vineyard, Massachusetts, is the site of a sustained outbreak of tularemia due to Francisella tularensis tularensis. Dog ticks, Dermacentor variabilis, appear to be critical in the perpetuation of the agent there. Tularemia has long been characterized as an agent of natural focality, stably persisting in characteristic sites of transmission, but this suggestion has never been rigorously tested. Accordingly, we sought to identify a natural focus of transmission of the agent of tularemia by mapping the distribution of PCR-positive ticks. From 2004 to 2007, questing D. variabilis were collected from 85 individual waypoints along a 1.5 km transect in a field site on Martha's Vineyard. The positions of PCR-positive ticks were then mapped using ArcGIS. Cluster analysis identified an area approximately 290 meters in diameter, 9 waypoints, that was significantly more likely to yield PCR-positive ticks (relative risk 3.3, P = 0.001) than the rest of the field site. Genotyping of F. tularensis using variable number tandem repeat (VNTR) analysis on PCR-positive ticks yielded 13 different haplotypes, the vast majority of which was one dominant haplotype. Positive ticks collected in the cluster were 3.4 times (relative risk = 3.4, P<0.0001) more likely to have an uncommon haplotype than those collected elsewhere from the transect. We conclude that we have identified a microfocus where the agent of tularemia stably perpetuates and that this area is where genetic diversity is generated

Persistence of Pathogens with Short Infectious Periods in Seasonal Tick Populations: The Relative Importance of Three Transmission Routes

BACKGROUND: The flaviviruses causing tick-borne encephalitis (TBE) persist at low but consistent levels in tick populations, despite short infectious periods in their mammalian hosts and transmission periods constrained by distinctly seasonal tick life cycles. In addition to systemic and vertical transmission, cofeeding transmission has been proposed as an important route for the persistence of TBE-causing viruses. Because cofeeding transmission requires ticks to feed simultaneously, the timing of tick activity may be critical to pathogen persistence. Existing models of tick-borne diseases do not incorporate all transmission routes and tick seasonality. Our aim is to evaluate the influence of seasonality on the relative importance of different transmission routes by using a comprehensive mathematical model. METHODOLOGY/PRINCIPAL FINDINGS: We developed a stage-structured population model that includes tick seasonality and evaluated the relative importance of the transmission routes for pathogens with short infectious periods, in particular Powassan virus (POWV) and the related "deer tick virus," emergent encephalitis-causing flaviviruses in North America. We used the next generation matrix method to calculate the basic reproductive ratio and performed elasticity analyses. We confirmed that cofeeding transmission is critically important for such pathogens to persist in seasonal tick populations over the reasonable range of parameter values. At higher but still plausible rates of vertical transmission, our model suggests that vertical transmission can strongly enhance pathogen prevalence when it operates in combination with cofeeding transmission. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that the consistent prevalence of POWV observed in tick populations could be maintained by a combination of low vertical, intermediate cofeeding and high systemic transmission rates. When vertical transmission is weak, nymphal ticks support integral parts of the transmission cycle that are critical for maintaining the pathogen. We also extended the model to pathogens that cause chronic infections in hosts and found that cofeeding transmission could contribute to elevating prevalence even in these systems. Therefore, the common assumption that cofeeding transmission is not relevant in models of chronic host infection, such as Lyme disease, could lead to underestimating pathogen prevalence

Combining PPI with qualitative research to engage ‘harder-to-reach’ populations: service user groups as co-applicants on a platform study for a trial

Abstract Background: Patient and public involvement (PPI) in all research studies is recommended from the earliest point and in as many stages as possible. Qualitative research is also recommended in the early stages of designing. complex intervention trials. Combining both together might enable inclusion of ‘harder-to-reach’ perspectives from the target population(s), particularly when the research is intended for their benefit. However, the interface between PPI and qualitative research has received little attention. Methods: In a multi-disciplinary, mixed methods study to inform the design of incentive trials for smoking cessation in pregnancy and breastfeeding, we combined PPI and qualitative research, with some overlap. Mother and baby groups from two geographically separate disadvantaged areas, with diverse experiences of the smoking and breastfeeding, but no training or previous involvement in research, were recruited as PPI research grant co-applicants. An iterative partnership approach facilitated involvement in research conduct and design across all project phases. Group PPI members were also invited to contribute to more formal qualitative data collection, as and when indicated by the research questions, and emerging analysis. Results: We engaged with ‘harder-to-reach’ women in mother and baby group settings, rather than in academic or home environments. These settings were relaxed and informal, which facilitated rapport-building, disclosures of unexpected information and maintained trust. 21 women participated in standard PPI activities: feedback on study protocols and documents; piloting questionnaires and interview schedules. PPI members voiced some different perspectives from those captured within the qualitative dataset. 19 participated in focused qualitative research. Novel aspects were audio recorded PPI discussions, which contributed qualitative data; first, to interpret systematic review findings and construct intervention vignettes for use in the qualitative research; second, to assist with recruitment to improve sample diversity in the formal qualitative dataset; and third, to translate theory and findings presented in a researcher generated logic model into a lay tool. This had face validity for potential trial participants and used the metaphor of a ladder. Conclusions: Combining and overlapping PPI and qualitative research added ‘harder-to-reach’ contributions, sample diversity, trust and engagement in creative approaches beyond what could be achieved through PPI or qualitative research alone. (350/350

Expression of Distal-less, dachshund, and optomotor blind in Neanthes arenaceodentata (Annelida, Nereididae) does not support homology of appendage-forming mechanisms across the Bilateria

The similarity in the genetic regulation of arthropod and vertebrate appendage formation has been interpreted as the product of a plesiomorphic gene network that was primitively involved in bilaterian appendage development and co-opted to build appendages (in modern phyla) that are not historically related as structures. Data from lophotrochozoans are needed to clarify the pervasiveness of plesiomorphic appendage forming mechanisms. We assayed the expression of three arthropod and vertebrate limb gene orthologs, Distal-less (Dll), dachshund (dac), and optomotor blind (omb), in direct-developing juveniles of the polychaete Neanthes arenaceodentata. Parapodial Dll expression marks premorphogenetic notopodia and neuropodia, becoming restricted to the bases of notopodial cirri and to ventral portions of neuropodia. In outgrowing cephalic appendages, Dll activity is primarily restricted to proximal domains. Dll expression is also prominent in the brain. dac expression occurs in the brain, nerve cord ganglia, a pair of pharyngeal ganglia, presumed interneurons linking a pair of segmental nerves, and in newly differentiating mesoderm. Domains of omb expression include the brain, nerve cord ganglia, one pair of anterior cirri, presumed precursors of dorsal musculature, and the same pharyngeal ganglia and presumed interneurons that express dac. Contrary to their roles in outgrowing arthropod and vertebrate appendages, Dll, dac, and omb lack comparable expression in Neanthes appendages, implying independent evolution of annelid appendage development. We infer that parapodia and arthropodia are not structurally or mechanistically homologous (but their primordia might be), that Dll’s ancestral bilaterian function was in sensory and central nervous system differentiation, and that locomotory appendages possibly evolved from sensory outgrowths

Collaborating with consumer and community representatives in health and medical research in Australia: results from an evaluation

<p>Abstract</p> <p>Objective</p> <p>To collaborate with consumer and community representatives in the <it>Alcohol and Pregnancy Project </it>from 2006-2008 <url>http://www.ichr.uwa.edu.au/alcoholandpregnancy</url> and evaluate researchers' and consumer and community representatives' perceptions of the process, context and impact of consumer and community participation in the project.</p> <p>Methods</p> <p>We formed two reference groups and sought consumer and community representatives' perspectives on all aspects of the project over a three year period. We developed an evaluation framework and asked consumer and community representatives and researchers to complete a self-administered questionnaire at the end of the project.</p> <p>Results</p> <p>Fifteen researchers (93.8%) and seven (53.8%) consumer and community representatives completed a questionnaire. Most consumer and community representatives agreed that the process and context measures of their participation had been achieved. Both researchers and consumer and community representatives identified areas for improvement and offered suggestions how these could be improved for future research. Researchers thought consumer and community participation contributed to project outputs and outcomes by enhancing scientific and ethical standards, providing legitimacy and authority, and increasing the project's credibility and participation. They saw it was fundamental to the research process and acknowledged consumer and community representatives for their excellent contribution. Consumer and community representatives were able to directly influence decisions about the research. They thought that consumer and community participation had significant influence on the success of project outputs and outcomes.</p> <p>Conclusions</p> <p>Consumer and community participation is an essential component of good research practice and contributed to the <it>Alcohol and Pregnancy Project </it>by enhancing research processes, outputs and outcomes, and this participation was valued by community and consumer representatives and researchers. The National Health and Medical Research Council in Australia expects researchers to work in partnership and involve consumer and community representatives in health and medical research, and to evaluate community and consumer participation. It is important to demonstrate whether consumer and community participation makes a difference to health and medical research.</p