BASHH 2018 UK national audit of HIV partner notification.

HIV partner notification (PN) is a highly effective strategy to identify people living with undiagnosed HIV infection. This national audit of HIV PN is against the 2015 British Association of Sexual Health and HIV (BASHH)/British HIV Association (BHIVA)/Society of Sexual Health Advisers (SHAA)/National AIDS Trust (NAT) HIV PN standards, developed in response to the 2013 BASHH/BHIVA national HIV PN audit. We report significant improvements in the number of contacts tested per index case, likely due, in part, to clearer definitions as well as better ascertainment and reporting. There remains scope for improvement with informing and testing contactable contacts. Recommendations from this audit include further refinement of definitions and development of a national proforma for HIV PN.

What impact has tendering had on trainees? Results of a national survey by British Association for Sexual Health and HIV Trainees' Collaborative for audit, research and quality improvement projects.

In April 2013, local authorities gained responsibility for commissioning sexual health services in England. With many services going out to tender and resultant change in services or service provider, there is anecdotal evidence that this has impacted on the education, training and morale of genitourinary medicine (GUM) trainees. The aim of this study was to evaluate the impact of tendering on GUM trainees. An electronic survey designed by the British Association for Sexual Health and HIV Trainees' Collaborative for Audit, Research and Quality Improvement Projects (T-CARQ) was distributed to GUM trainees and newly appointed consultants. Eighty-two individuals responded (74% GUM trainees, 25% newly appointed consultants, 1% locum appointed for service). Sixty-three per cent (45/72) had experience of training within a service which was being tendered. Of these, 59% (24/41) felt their training was not considered during the tendering process and 20% (8/41) felt that it was. Forty-four per cent (18/41) felt adequately supported. Thirty per cent (12/40) reported active participation in the tendering process. On a scale of 0 (no impact) to 5 (major impact), the median score for impact of tendering on training was 2. The positive/negative impact of tendering on different training elements was rated: other than management experience the overall impact on all parameters was negative, namely morale, senior support and education. In conclusion, this survey describes the variable impact of service tendering on GUM training. Our recommendations for maintaining training standards despite tendering include actively involving trainees and education partners, inclusion of specialist GUM training in service specifications, development of guidance for commissioners and services for the management of GUM training within tendering.

Disulfiram-induced cytotoxicity and endo-lysosomal sequestration of zinc in breast cancer cells.

Disulfiram, a clinically used alcohol-deterrent has gained prominence as a potential anti-cancer agent due to its impact on copper-dependent processes. Few studies have investigated zinc effects on disulfiram action, despite it having high affinity for this metal. Here we studied the cytotoxic effects of disulfiram in breast cancer cells, and its relationship with both intra and extracellular zinc. MCF-7 and BT474 cancer cell lines gave a striking time-dependent biphasic cytotoxic response between 0.01 and 10 µM disulfiram. Co-incubation of disulfiram with low-level zinc removed this effect, suggesting that availability of extracellular zinc significantly influences disulfiram efficacy. Live-cell confocal microscopy using fluorescent endocytic probes and the zinc dye Fluozin-3 revealed that disulfiram selectively and rapidly increased zinc levels in endo-lysosomes. Disulfiram also caused spatial disorganization of late endosomes and lysosomes, suggesting they are novel targets for this drug. This relationship between disulfiram toxicity and ionophore activity was consolidated via synthesis of a new disulfiram analog and overall we demonstrate a novel mechanism of disulfiram-cytotoxicity with significant clinical implications for future use as a cancer therapeutic.

Cellular entry of nanoparticles via serum sensitive clathrin-mediated endocytosis, and plasma membrane permeabilization.

Increasing production and application of nanomaterials raises significant questions regarding the potential for cellular entry and toxicity of nanoparticles. It was observed that the presence of serum reduces the cellular association of 20 nm carboxylate-modified fluorescent polystyrene beads up to 20-fold, relative to cells incubated in serum-free media. Analysis by confocal microscopy demonstrated that the presence of serum greatly reduces the cell surface association of nanoparticles, as well as the potential for internalization. However, both in the presence and absence of serum, nanoparticle entry depends upon clathrin-mediated endocytosis. Finally, experiments performed with cells cooled to 4°C suggest that a proportion of the accumulation of nanoparticles in cells was likely due to direct permeabilization of the plasma membrane.

An agarose spot chemotaxis assay for chemokine receptor antagonists.

INTRODUCTION: Chemokines are important players in directing the migration of cancer cells as part of the metastatic process. The aim of this study is to develop an easy-to-perform, reliable, and inexpensive assay for rapid analysis of anti-chemotactic activity of chemokine antagonists under a number of experimental conditions. METHODS: An agarose spot containing the chemokine chemoattractant is applied to a glass petri dish. Live cells in a media, both with and without a chemokine antagonist, are added to the dish and, following cell adhesion, the migration under the agarose spot is observed and analysed by microscopy. RESULTS: In the absence of CXCL12 in the agarose, no migration under the agarose spot is detected. In the presence of CXCL12, significant migration under the agarose spot is observed which can be retarded if a neutralising monoclonal antibody or a small molecule antagonist is added to the media. DISCUSSION: This experimental configuration is a reliable, inexpensive and easy-to-perform chemotaxis assay, which enables assessment of the activity of CXCR4 antagonists.

State of the arctic conference 2010: international perspectives on progress of research responsive to decision-makers' information needs.

The SoA conference emphasized that urgent questions posed by society and decision-makers in response to rapid Arctic change require that Arctic research address the broader concepts of sustainability as well as adaptation to and mitigation of interrelated environmental and socioeconomic change. Murray et al. (submitted) explore progress made in this context. The SoA meeting demonstrated significant progress by the Arctic community of scientists and stakeholders in meeting this challenge, as well as the need to better engage the private sector and find more effective ways to partner with relevant research activities outside of the polar regions.

An agarose spot assay for chemotactic invasion.

The directed motility of cells toward the source of a soluble chemical (chemotaxis) plays a role in events ranging from immune function to cancer progression. Numerous chemotaxis assays are commonly employed, yet none provides an optimal combination of the relevant parameters. The ideal chemotaxis assay for use in the analysis of cells crawling across a planar surface should be cost-effective, simple to perform, and suitable for high-throughput multiplexing, as well as permit alteration of experimental conditions during cell motility. Here we describe a novel chemotaxis assay based upon the invasion of cells into agarose spots into which chemoattractants are suspended. Our studies demonstrate that this system assays chemotaxis and not chemokinesis, and provide proof-of-principle for drug screening studies as well as analysis through high-resolution cellular imaging.