Guy's and St Thomas' NHS Foundation Trust

About: Guy's and St Thomas' NHS Foundation Trust is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Randomized controlled trial. The organization has 7686 authors who have published 9631 publications receiving 399353 citations. The organization is also known as: Guy's and St Thomas' National Health Service Foundation Trust & Guy's and St Thomas' National Health Service Trust.

Alpha‐6 integrin is necessary for the tumourigenicity of a stem cell‐like subpopulation within the MCF7 breast cancer cell line

Abstract: The identification of mammary epithelial stem cells raises the hypothesis that these cells may be crucial in the pathogenesis of breast cancer. To further support this, a highly tumourigenic sub-population of cancer cells has recently been identified in primary and metastatic breast cancer samples. In this study, a sub-population of cells displaying features normally attributed to stem cells was identified within the breast cancer cell line MCF-7. This sub-population is capable of growth in anchorage-independent conditions as spherical organoids, displays resistance to proapoptotic agents and significantly greater tumourigenicity than its parental line, with as few as 1,000 cells able to form tumours in immunodeficient mice. Cells within this sub-population can be enriched by serial passages in anchorage-independence, and are characterized by over-expression of the adhesion molecule 6-integrin. Alpha-6 integrin proves to be required for the growth and survival of these cells, as the knockdown of ITGA6 causes mammosphere-derived cells to lose their ability to grow as mammospheres and abrogates their tumourigenicity in mice. These findings support the existence of a highly tumourigenic sub-population in breast cancer cells. Furthermore, it shows 6-integrin as a potential therapeutic target aimed at tumour-generating subsets of breast cancer cells.

Mutations in TJP2 cause progressive cholestatic liver disease

Abstract: Elucidating genetic causes of cholestasis has proved to be important in understanding the physiology and pathophysiology of the liver. Here we show that protein-truncating mutations in the tight junction protein 2 gene (TJP2) cause failure of protein localization and disruption of tight-junction structure, leading to severe cholestatic liver disease. These findings contrast with those in the embryonic-lethal knockout mouse, highlighting differences in redundancy in junctional complexes between organs and species.

Purchasing ‘legal highs’ on the Internet—is there consistency in what you get?

Abstract: Background: The supply of recreational drugs has changed and users increasingly buy ‘legal highs’ over the Internet. Use of these is common and there is a potential for significant toxicity associated with their use. Aim: To determine the content of legal highs available for purchase in the UK and whether the content of these remains consistent. Methods: Twenty-six legal highs were purchased monthly from five different Internet sites over 6 months. These were analysed to determine the drugs in the products and whether there were any changes in their content over this time period. Results: All products were supplied initially, but there was a decline in supply of products month by month. The following drug classes were detected: piperazines, cathinones, caffeine/ephedrine or products in which no psychoactive drugs were detected. Of the products supplied on more than one occasion, 15 (75%) contained the same compounds on each occasion. In three products there was a change in the piperazine detected, with 1-benzylpiperazine being substituted for 1-methyl-4-benzylpiperazine or vice versa. In two other products there was a cathinone [4-fluorophenylpiperazine (pFPP) or 3-fluromethcathinone (3FMC)] detected in products purchased in Month 1 that was not present in the products purchased in subsequent months. Conclusions: Whilst there was no variation in the composition of most legal highs supplied over 6 month, there was significant variation in the piperazine or cathinone content of one quarter of the products. This variation could be of clinical significance as the cathinone and piperazine products can be associated with significant toxicity.

Factors influencing recruitment to research: qualitative study of the experiences and perceptions of research teams

Abstract: Background Recruiting the required number of participants is vital to the success of clinical research and yet many studies fail to achieve their expected recruitment rate. Increasing research participation is a key agenda within the NHS and elsewhere, but the optimal methods of improving recruitment to clinical research remain elusive. The aim of this study was to identify the factors that researchers perceive as influential in the recruitment of participants to clinically focused research.

Evolutionary Genetics of Human Enterovirus 71: Origin, Population Dynamics, Natural Selection, and Seasonal Periodicity of the VP1 Gene

Abstract: Human enterovirus 71 (EV-71) is one of the major etiologic causes of hand, foot, and mouth disease (HFMD) among young children worldwide, with fatal instances of neurological complications becoming increasingly common. Global VP1 capsid sequences (n 628) sampled over 4 decades were collected and subjected to comprehensive evolutionary analysis using a suite of phylogenetic and population genetic methods. We estimated that the common ancestor of human EV-71 likely emerged around 1941 (95% confidence interval [CI], 1929 to 1952), subsequently diverging into three genogroups: B, C, and the now extinct genogroup A. Genealogical analysis revealed that diverse lineages of genogroup B and C (subgenogroups B1 to B5 and C1 to C5) have each circulated cryptically in the human population for up to 5 years before causing large HFMD outbreaks, indicating the quiescent persistence of EV-71 in human populations. Estimated phylogenies showed a complex pattern of spatial structure within well-sampled subgenogroups, suggesting endemicity with occasional lineage migration among locations, such that past HFMD epidemics are unlikely to be linked to continuous transmission of a single strain of virus. In addition, rises in genetic diversity are correlated with the onset of epidemics, driven in part by the emergence of novel EV-71 subgenogroups. Using subgenogroup C1 as a model, we observe temporal strain replacement through time, and we investigate the evidence for positive selection at VP1 immunogenic sites. We discuss the consequences of the evolutionary dynamics of EV-71 for vaccine design and compare its phylodynamic behavior with that of influenza virus.