Neoblast-like stem cells of Fasciola hepatica.

The common liver fluke (Fasciola hepatica) causes the disease fasciolosis, which results in considerable losses within the global agri-food industry. There is a shortfall in the drugs that are effective against both the adult and juvenile life stages within the mammalian host, such that new drug targets are needed. Over the last decade the stem cells of parasitic flatworms have emerged as reservoirs of putative novel targets due to their role in development and homeostasis, including at host-parasite interfaces.

Discovery of long non-coding RNAs in the liver fluke, Fasciola hepatica.

Long non-coding (lnc)RNAs are a class of eukaryotic RNA that do not code for protein and are linked with transcriptional regulation, amongst a myriad of other functions. Using a custom in silico pipeline we have identified 6,436 putative lncRNA transcripts in the liver fluke parasite, Fasciola hepatica, none of which are conserved with those previously described from Schistosoma mansoni. F.

Daily angina documentation versus subsequent recall: development of a symptom smartphone app.

Aims: The traditional approach to documenting angina outcomes in clinical trials is to ask the patient to recall their symptoms at the end of a month. With the ubiquitous availability of smartphones and tablets, daily contemporaneous documentation might be possible.

Methods And Results: The ORBITA-2 symptom smartphone app was developed with a user-centred iterative design and testing cycle involving a focus group of previous ORBITA participants.

Transcriptomic analysis supports a role for the nervous system in regulating growth and development of Fasciola hepatica juveniles.

Fasciola spp. liver flukes have significant impacts in veterinary and human medicine. The absence of a vaccine and increasing anthelmintic resistance threaten sustainable control and underscore the need for novel flukicides.

The Scanning Fiber Endoscope: A Novel Surgical and High-Resolution Imaging Device for Intracranial Neurosurgery.

Background: The scanning fiber endoscope (SFE) is a novel medical imaging device that has been used in various vascular beds as a form of angioscopy, as well as in tracts and duct systems for endoluminal imaging. Owing to its miniaturized form, high resolution, and flexibility, it has demonstrated success in imaging across a wide range of diagnostic applications.

Objective: To demonstrate, by performing a third ventriculostomy and visualizing the cranial nerves and brainstem anatomy, that, without modification, the SFE can be used through a transcranial approach in a therapeutic intraventricular neurosurgical application.

Pan-phylum Analyses of Nematode Endocannabinoid Signalling Systems Highlight Novel Opportunities for Parasite Drug Target Discovery.

The endocannabinoid signalling (ECS) system is a complex lipid signalling pathway that modulates diverse physiological processes in both vertebrate and invertebrate systems. In nematodes, knowledge of endocannabinoid (EC) biology is derived primarily from the free-living model species , where ECS has been linked to key aspects of nematode biology. The conservation and complexity of nematode ECS beyond is largely uncharacterised, undermining the understanding of ECS biology in nematodes including species with key importance to human, veterinary and plant health.

Developmental Regulation and Functional Prediction of microRNAs in an Expanded miRNome.

The liver fluke, , is a global burden on the wellbeing and productivity of farmed ruminants, and a zoonotic threat to human health. Despite the clear need for accelerated discovery of new drug and vaccine treatments for this pathogen, we still have a relatively limited understanding of liver fluke biology and host interactions. Noncoding RNAs, including micro (mi)RNAs, are key to transcriptional regulation in all eukaryotes, such that an understanding of miRNA biology can shed light on organismal function at a systems level.

A double-blind randomised placebo-controlled trial of percutaneous coronary intervention for the relief of stable angina without antianginal medications: design and rationale of the ORBITA-2 trial.

Percutaneous coronary intervention (PCI) is frequently performed for stable angina. However, the first blinded trial, ORBITA, did not show a placebo-controlled increment in exercise time in patients with single-vessel disease, at 6 weeks, on maximal antianginal therapy. ORBITA-2 will assess the placebo-controlled efficacy of PCI on angina frequency in patients with single- or multivessel disease, at 12 weeks, on no antianginal therapy.

characterisation of the complete Ly6 protein family in supported through transcriptomics of the newly-excysted juveniles.

is one of the aetiological trematodes associated with fascioliasis, which heavily impacts food-production systems and human and animal welfare on a global scale. In the absence of a vaccine, fascioliasis control and treatment is restricted to pasture management, such as clean grazing, and a limited array of chemotherapies, to which signs of resistance are beginning to appear. Research into novel control strategies is therefore urgently required and the advent of 'omics technologies presents considerable opportunity for novel drug and vaccine target discovery.

Phylum-Spanning Neuropeptide GPCR Identification and Prioritization: Shaping Drug Target Discovery Pipelines for Nematode Parasite Control.

Nematode parasites undermine human health and global food security. The frontline anthelmintic portfolio used to treat parasitic nematodes is threatened by the escalation of anthelmintic resistance, resulting in a demand for new drug targets for parasite control. Nematode neuropeptide signalling pathways represent an attractive source of novel drug targets which currently remain unexploited.

2,4 dinitrophenol: It's not just for men.

Background: 2,4 dinitrophenol (DNP) is an organic compound which causes thermogenesis resulting in fat burning and weight loss. Although not licensed for human consumption, the globalised access to and information about this compound on the internet has prompted a renewed interest in DNP making it readily available to purchase online.  Studies into user experiences remain scarce and much of the previous literature has focused on DNP use in male dominated bodybuilding communities.

Molecular characterisation and vaccine efficacy of two novel developmentally regulated surface tegument proteins of Fasciola hepatica.

The surface tegument of Fasciola hepatica is a crucial tissue due to its key role at the host-parasite interface. We characterised three novel proteins, termed Fhteg1, Fhteg5 and Fhteg8, that are found in the tegument membrane fraction of adult F. hepatica.

RNA interference dynamics in juvenile Fasciola hepatica are altered during in vitro growth and development.

For over a decade RNA interference (RNAi) has been an important molecular tool for functional genomics studies in parasitic flatworms. Despite this, our understanding of RNAi dynamics in many flatworm parasites, such as the temperate liver fluke (Fasciola hepatica), remains rudimentary. The ability to maintain developing juvenile fluke in vitro provides the opportunity to perform functional studies during development of the key pathogenic life stage.

Post-genomic progress in helminth parasitology.

Helminth parasitology is an important discipline, which poses often unique technical challenges. One challenge is that helminth parasites, particularly those in humans, are often difficult to obtain alive and in sufficient quantities for study; another is the challenge of studying these organisms in vitro - no helminth parasite life cycle has been fully recapitulated outside of a host. Arguably, the key issue retarding progress in helminth parasitology has been a lack of experimental tools and resources, certainly relative to the riches that have driven many parasitologists to adopt free-living model organisms as surrogate systems.

Evaluation of Novel Imaging Devices for Nanoparticle-Mediated Fluorescence-Guided Lung Tumor Therapy.

Background: Nonsurgical and minimally invasive approaches for early-stage peripheral lung cancer are needed to avoid the known morbidity of surgical resection, particularly in high-risk patients. We previously demonstrated the utility of multifunctional porphyrin-phospholipid nanoparticles (porphysomes) for fluorescence imaging and phototherapy after preferential accumulation into tumors. The objective of this study was to demonstrate the feasibility of porphysome-mediated imaging and photothermal therapy using a newly developed fiberscope and thoracoscope.

Can CRISPR help in the fight against parasitic worms?

The first reports of CRISPR/Cas9 genome editing in flatworms could usher in a new era of research on these dangerous human parasites.

High-Resolution Scanning Fiber Angioscopy as an Adjuvant to Fluoroscopy During Endovascular Interventions.

Purpose: To demonstrate the feasibility and potential utility of high-resolution angioscopy during common endovascular interventions.

Methods: A 3.7-F scanning fiber angioscope was used in 6 Yorkshire pigs to image branch vessel selection, subintimal dissection, wire snaring, and stent placement.

Profiling G protein-coupled receptors of Fasciola hepatica identifies orphan rhodopsins unique to phylum Platyhelminthes.

G protein-coupled receptors (GPCRs) are established drug targets. Despite their considerable appeal as targets for next-generation anthelmintics, poor understanding of their diversity and function in parasitic helminths has thwarted progress towards GPCR-targeted anti-parasite drugs. This study facilitates GPCR research in the liver fluke, Fasciola hepatica, by generating the first profile of GPCRs from the F.

Tissue-specific transcriptome analyses provide new insights into GPCR signalling in adult Schistosoma mansoni.

Schistosomes are blood-dwelling trematodes with global impact on human and animal health. Because medical treatment is currently based on a single drug, praziquantel, there is urgent need for the development of alternative control strategies. The Schistosoma mansoni genome project provides a platform to study and connect the genetic repertoire of schistosomes to specific biological functions essential for successful parasitism.

Reasons to Be Nervous about Flukicide Discovery.

The majority of anthelmintics dysregulate neuromuscular function, a fact most prominent for drugs against nematode parasites. In contrast to the strong knowledge base for nematode neurobiology, resource and tool deficits have prevented similar advances in flatworm parasites since those driven by bioimaging, immunocytochemistry, and neuropeptide biochemistry 20-30 years ago. However, recent developments are encouraging a renaissance in liver fluke neurobiology that can now support flukicide discovery.

Stimulating Neoblast-Like Cell Proliferation in Juvenile Fasciola hepatica Supports Growth and Progression towards the Adult Phenotype In Vitro.

Fascioliasis (or fasciolosis) is a socioeconomically important parasitic disease caused by liver flukes of the genus Fasciola. Flukicide resistance has exposed the need for new drugs and/or a vaccine for liver fluke control. A rapidly improving 'molecular toolbox' for liver fluke encompasses quality genomic/transcriptomic datasets and an RNA interference platform that facilitates functional genomics approaches to drug/vaccine target validation.

Repair of popliteal aneurysm and spontaneous arteriovenous fistula in a patient with Marfan syndrome.

Isolated extremity arterial aneurysms remain a rare entity, and the development of a spontaneous arteriovenous fistula from such an aneurysmal segment in a young patient should prompt a search for an underlying genetic predisposition. Endovascular repair of aneurysms or arteriovenous fistulas in the popliteal artery is appropriate in select populations; however, open repair allows for a more durable reconstruction of both the arterial and any involved venous segments in patients who can tolerate the procedure.