Multidetector CT improving surgical outcomes in breast cancer (MISO-BC) : a randomised controlled trial

Background: Early diagnosis of malignant axillary nodes in breast cancer guides the extent of axillary surgery: patients with known axillary malignancy receive a more extensive single operation at the same time as surgery to their breast. A multicentre randomised controlled trial assessed whether a Computed Tomography (CT) scan of the axilla could more accurately diagnose malignant axillary lymph node involvement in patients with newly diagnosed breast cancer when compared to usual care. Methods: Patients with newly diagnosed breast cancer (identified via screening and symptomatic pathways) at two NHS Trusts in the North East of England were recruited and randomised in equal numbers. Both groups received routine diagnostic and surgical care. In addition, one group received a CT scan of their axilla on the same side as the breast cancer. The primary endpoint was the need to undergo a second axillary surgical procedure. Findings: The trial recruited 297 patients of whom 291 contributed to findings. The proportion of patients undergoing a second operation was similar (CT vs UC: 19.4% vs. 19.7%; CT-UC: −0.3%, 95%CI: = −9.5% to 8.9%, χ2 [1]: p = 1.00). Patients in the two groups were similar before treatment, had similar types and grade of cancer, experienced similar patterns of post-operative complications and reported similar experiences of care. Interpretation: CT scan-guided care did not result in a change in the number of patients requiring a second operation; similar numbers of patients needed further axillary surgery in both groups. New diagnostic imaging technologies regularly enter NHS centres. It is important these are evaluated rigorously before becoming routine care

Long-term evaluation of AAV-mediated sFlt-1 gene therapy for ocular neovascularization in mice and monkeys

Vascular endothelial growth factor (VEGF) is one of the major mediators of retinal ischemia-associated neovascularization. We have shown here that adeno-associated virus (AAV)-mediated expression of sFIt-1, a soluble form of the Flt-1 VEGF receptor, was maintained for up to 8 and 17 months postinjection in mice and in monkeys, respectively. The expression of sFIt-1 was associated with the long-term (8 months) regression of neovascular vessels in 85% of trVEGF029 eyes. In addition, it resulted in the maintenance of retinal morphology, as the majority of the treated trVEGF029 eyes (75%) retained high numbers of photoreceptors, and in retinal function as measured by electroretinography. AAV-mediated expression of sFIt-1 prevented the development of laser photocoagulation-incluced choroidal neovascularization in all treated monkey eyes. There were no clinically or histologically detectable signs of toxicity present in either animal model following AAV.sFlt injection. These results suggest that AAV-mediated secretion gene therapy could be considered for treatment of retinal and choroidal neovascularizations

Biosynthesis of fungal indole alkaloids

This review provides a summary of recent research advances in elucidating the biosynthesis of fungal indole alkaloids. Different strategies used to incorporate and derivatize the indole/indoline moieties in various families of fungal indole alkaloids will be discussed, including tryptophan-containing nonribosomal peptides and polyketide-nonribosomal peptide hybrids; and alkaloids derived from other indole building blocks. This review also includes discussion regarding the downstream modifications that generate chemical and structural diversity among indole alkaloids

Developing Bioreactors to Host Joint-Derived Tissues That Require Mechanical Stimulation

Demographics of the Western Societies points toward an elderly population in need of research on replacement parts for joints and their components, such as the meniscus, cartilage, ligaments, tendons, and intervertebral discs. There is a lack of basic research to predict treatment options before degeneration or inflammation has progressed, and at late stages, when regeneration might not be an option anymore. Thus, to achieve a better understanding of the current specific problems in orthopedic research, there is a need for clinically relevant mechanobiological models. Animal experiments, especially those on large animals, are costly and, in some cases, doubtful as regards clinical translation. Ex vivo bioreactors that allow biomechanical loading are aimed to mimic the in vivo situation of critical joints that are prone to failure. These tissues often require unique adaptations prior and during organ culture as these are often under mechanical forces in situ. On the one hand, ex vivo organ cultures are limited in regarding the size and cell numbers that can be kept alive and the duration of experiments. However, a strong asset of these cultures is the use of primary human material, which is a chance to provide more translational relevant results. Within this book chapter, we give a brief history of general concepts for bioreactor constructions in the field of orthopedic research and give some recent examples for tendons, the knee joint and the intervertebral disc. We offer a summary of the current state of the art, pitfalls and limitations in the design and the future challenges