Abstract: Given improvements in viral vector design, production and efficiency of transduction in the central nervous system (CNS), as well as increased knowledge of neuropathological mechanisms in neurological disorders, success in treating a CNS disorder with gene transfer seems inevitable. Several different vector systems have been studied extensively and the adeno-associated viral vector system has been utilized in most early stage clinical trials in neurological disorders. Other vector systems, such as lentivirus, adenovirus, and herpes simplex virus are also viable vector platforms that should fill significant clinical niches based on their specific characteristics. In addition to the choice of the appropriate vector, the proper choice of transgene for the appropriate strategy to treat a neurological disorder is also critical. The example of glial cell line-derived neurotrophic factor ligands to treat Parkinson's disease is used to illustrate the importance of the interface between interpretation of pre-clinical data and consideration of the natural history of the disorder. This interface dictates the proper design of clinical trials that are capable of testing whether the treatment is actually successful. ... Read more

Abstract: According to the World Health Organization, approximately 220 million people worldwide have type 2 diabetes mellitus. Patients with type 2 diabetes not only have a chronic disease to cope with, they are also at increased risk for coronary heart disease, peripheral vascular disease, retinopathy, nephropathy, and neuropathy. The exact causes of type 2 diabetes are still not clear. Since the 17^th century, it has been suggested that emotional stress plays a role in the etiology of type 2 diabetes mellitus. So far, review studies have mainly focused on depression as a risk factor for the development of type 2 diabetes mellitus. Yet, chronic emotional stress is an established risk factor for the development of depression. The present review provides an overview of mainly prospective epidemiological studies that have investigated the associations between different forms of emotional stress and the development of type 2 diabetes mellitus. Results of longitudinal studies suggest that not only depression but also general emotional stress and anxiety, sleeping problems, anger, and hostility are associated with an increased risk for the development of type 2 diabetes. Conflicting results were found regarding childhood neglect, life events, and work stress. It is important to emphasize that publication-bias may have occurred, resulting from "fishing-expeditions," where authors search their data for significant associations. Publication bias may also be caused by the tendency of reviewers and Editors to reject manuscripts with negative results for publication. It is therefore essential that research groups, who aim to conduct a new epidemiological cohort study, prospectively describe and publish the design of their study. Future research should focus on identifying mechanisms linking different forms of stress and incident type 2 diabetes. ... Read more