A phenotypic screen of the Global Health Priority Box identifies an insecticide with anthelmintic activity.

Background: Infection with parasitic nematodes (helminths), particularly those of the order Strongylida (such as Haemonchus contortus), can cause significant and burdensome diseases in humans and animals. Widespread drug (anthelmintic) resistance in livestock parasites, the absence of vaccines against most of these nematodes, and a lack of new and effective chemical entities on the commercial market demands the discovery of new anthelmintics. In the present study, we searched the Global Health Priority Box (Medicines for Malaria Venture) for new candidates for anthelmintic development.

Structure-activity relationship and target investigation of 2-aryl quinolines with nematocidal activity.

Within the context of our anthelmintic discovery program, we recently identified and evaluated a quinoline derivative, called ABX464 or obefazimod, as a nematocidal candidate; synthesised a series of analogues which were assessed for activity against the free-living nematode Caenorhabditis elegans; and predicted compound-target relationships by thermal proteome profiling (TPP) and in silico docking. Here, we logically extended this work and critically evaluated the anthelmintic activity of ABX464 analogues on Haemonchus contortus (barber's pole worm) - a highly pathogenic nematode of ruminant livestock. First, we tested a series of 44 analogues on H.

Structure activity relationship and target prediction for ABX464 analogues in Caenorhabditis elegans.

Global challenges with treatment failures and/or widespread resistance in parasitic worms against commercially available anthelmintics lend impetus to the development of new anthelmintics with novel mechanism(s) of action. The free-living nematode Caenorhabditis elegans is an important model organism used for drug discovery, including the screening and structure-activity investigation of new compounds, and target deconvolution. Previously, we conducted a whole-organism phenotypic screen of the 'Pandemic Response Box' (from Medicines for Malaria Venture, MMV) and identified a hit compound, called ABX464, with activity against C.

The everolimus eluting Synergy Megatron drug-eluting stent platform: Early outcomes from the European Synergy Megatron Implanters' Registry.

Background: The Synergy Megatron is an everolimus-drug eluting stent that may offer advantages in the treatment of aorto-ostial disease and large proximal vessels.

Aims: To report the short- to medium-term clinical outcomes from the European Synergy Megatron Implanters' Registry.

Methods: This registry was an investigator-initiated study conducted at 14 European centers.

A High-Throughput Phenotypic Screen of the 'Pandemic Response Box' Identifies a Quinoline Derivative with Significant Anthelmintic Activity.

Parasitic nematodes cause diseases in livestock animals and major economic losses to the agricultural industry worldwide. Nematodes of the order Strongylida, including , are particularly important. The excessive use of anthelmintic compounds to treat infections and disease has led to widespread resistance to these compounds in nematodes, such that there is a need for new anthelmintics with distinctive mechanisms of action.

MRI rectal cancer in Australia and New Zealand: An audit from the PETACC-6 trial.

Introduction: An MRI audit substudy was conducted in patients who underwent an MRI prior to treatment in Australia and New Zealand as part of the PETACC-6 trial in locally advanced rectal cancer.

Methods: A total of 82 patients from 15 centres had rectal MRI scans reviewed for technique, data included in reports and comparison of reports with blinded central reporting by two experienced radiologists.

Results: In total, 82% performed minimum T2 sagittal and T2 axial oblique sequences.

Orbital Varix Thrombosis and Review of Orbital Vascular Anomalies in Blue Rubber Bleb Nevus Syndrome.

A 57-year-old woman with cutaneous manifestations of (BRBNS) presented with acute left proptosis and venous congestion secondary to thrombosis within a superior ophthalmic vein varix. Multiple phleboliths were noted in the contralateral right orbit, and an incidental right middle cerebral artery aneurysm. Her symptoms spontaneously resolved within a few days.

Rodent Aanat: intronic E-box sequences control tissue specificity but not rhythmic expression in the pineal gland.

Arylalkylamine N-acetyltransferase (Aanat) is the penultimate enzyme in the serotonin-N-acetylserotonin-melatonin pathway. It is nearly exclusively expressed in the pineal gland and the retina. A marked rhythm of Aanat gene expression in the rat pineal is mediated by cyclic AMP response elements located in the promoter and first intron.

The management of acute endocarditis.

Infective endocarditis (IE) is an infection, usually of bacterial aetiology, which can affect any part of the endovascular surface of the heart or large intrathoracic vessels but most commonly affects cardiac valves. Without treatment this condition is invariably fatal and even with treatment is associated with a high incidence of morbidity and mortality. This article looks at the difficulties in diagnosing IE and the investigations used to confirm the diagnosis.

Plasma concentrations and role of macrophage inflammatory protein-1alpha during chronic Schistosoma mansoni infection in humans.

Chemokines play an important role during granulomatous inflammation in murine models of Schistosoma mansoni infection. Here, the expression and possible roles of chemokines during human S. mansoni infection were examined.