Peer Reviewed: WebEase: Development of a Web-Based Epilepsy Self-Management Intervention

People with epilepsy must adopt many self-management behaviors, especially regarding medication adherence, stress management, and sleep quality. In response to the need for theory-based self-management programs that people with epilepsy can easily access, the WebEase Web site was created and tested for feasibility, acceptability, and usability. This article discusses the theoretical background and developmental phases of WebEase and lessons learned throughout the development process. The WebEase research team developed content for the Web site on the basis of social cognitive theory, the transtheoretical model of behavior change, and motivational interviewing. Formative research and development of the WebEase program included a literature search, computer use survey, a focus group, and review by content experts and consumers. The program has 2 main components: 1) the modules, which provide a tailored opportunity for learning, reflection, and goal setting, and 2) MyLog, a place to enter daily information.     

Modelling the monetary value of a QALY: a new approach based on UK data

Debate about the monetary value of a quality-adjusted life year (QALY) has existed in the health economics literature for some time. More recently, concern about such a value has arisen in UK health policy. This paper reports on an attempt to 'model' a willingness-to-pay-based value of a QALY from the existing value of preventing a statistical fatality (VPF) currently used in UK public sector decision making. Two methods of deriving the value of a QALY from the existing UK VPF are outlined: one conventional and one new. The advantages and disadvantages of each of the approaches are discussed as well as the implications of the results for policy and health economic evaluation methodology.     

Evidence for a direct subthalamo-cortical loop circuit in the rat

The subthalamic nucleus (STN), a major component of the basal ganglia (BG), plays a crucial role in motor activity and cognitive functions. In current models of the BG, the STN is considered to act by activating the γ-aminobutyric acid (GABA)ergic neurons of the BG output nuclei, thus inhibiting their thalamic and brain stem targets. However, in addition to the BG output nuclei, the STN has also been reported to innervate the cerebral cortex and the striatum. Here, the anatomo-functional organization of STN projections to the cerebral cortex was investigated using anatomical and electrophysiological approaches. First, wheatgerm agglutinin-conjugated horseradish peroxidase was injected into defined areas of the cerebral cortex to analyse the spatial distribution of retrogradely labelled STN neurons. The mode of cortical innervation by the STN was then determined using extracellular deposits of Phaseolus vulgaris -leucoagglutinin into the STN. Finally, the functional organization of the cortico-STN relationships was investigated by extracellularly recording single STN units antidromically driven from the cerebral cortex. Our results indicate that STN innervates the sensory-motor and prefrontal cortices, the densest projections terminating in cortical layers I–III of the orofacial motor area. The matching between the topographic distribution of subthalamo-cortical neurons and cortico-subthalamic projections forms the basis of a functional cortico-STN loop circuit that is partially opened. In pathological situations such as Parkinson's disease and epilepsy, the STN-cortex loop circuit might contribute to propagate pathological oscillations favouring the emergence of abnormal synchronized activities and a loss of functional selectivity in the cortico-BG network.     

The bitter end: the ubiquitin-proteasome system and cardiac dysfunction

Many elements contribute to congestive heart failure: changes in perfusion, hemodynamic stresses, alterations in calcium metabolism, and dysregulation of cell signaling pathways. Intervention in these processes forms the basis for current heart failure therapies. Nevertheless, heart failure is primarily a disease of wear and tear; despite everything we know about cardiac physiology and the clinical manifestations of heart failure, only in rare instances does therapy for heart failure normalize cardiac function. Proteins are especially prone to the forces of wear and tear in the heart because they are the primary mechanisms for stress sensing and force generation. Recent evidence supports a role for protein damage and impaired clearance of damaged proteins in the pathophysiology of human heart failure syndromes. The process of monitoring and protecting cardiac cells from accumulation of damaged proteins is known as protein quality control, and the molecular chaperone and ubiquitin-proteasome systems are the primary effectors of this process. Insights from protein quality-control strategies may lead to new concepts about prevention and treatment of human heart failure. This review provides a general overview of these pathways and their known and postulated roles in human heart failure syndromes, with a focus on providing a clinically oriented understanding of these fundamental mechanisms.     

Relation of neuroendocrine cells to transforming growth factor-alpha and epidermal growth factor receptor expression in gastric adenocarcinomas: Prognostic implications

The presence of neuroendocrine (NE) cells in gastric adenocarcinoma (GCa) is well documented, however, their significance is controversial. There is no evidence in the literature concerning the possible effect of these cells on the expression of TGF-a and EGFR, which are believed to confer growth advantage to tumor cells. 101 partial or total gastrectomy specimens from patients operated for conventional gastric adenocarcinoma were included in the study. In each case immunohistochemistry was performed on sequential tissue sections for chromogranin A (ChrA), TGF-a and EGFR. Samples were graded based on the number of ChrA-positive cells (0–3). TGF-a and EGFR expressions were evaluated according to both the intensity (0–2) and quantification of the positively stained areas (0–3). Follow-up data was available in 54 patients. Twenty-seven patients died of disease, while 27 patients were alive with a follow-up of at least 15 months. ChrA expression was detected in 54.4% of the tumor specimens. TGF-a was stained positively in 42.6% and EGFR in 49.5% of the cases. NE cells in GCa was related to TGF-a (p<0.0001) and EGFR expression (p<0.05), and TGF-a/EGFR coexpression (p<0.001). Among histopathologic variables, the presence of NE cells was significantly related to grade, stage and lymph node status. Although the presence of NE cells had no effect on survival, the expression of EGFR (p<0.0001) and TGF-a (p=0.002) were related to survival. The results of our study suggest that the presence of NE cells may have an effect on the expression of TGF-a and EGFR in GCa, and the autocrine mechanism between TGF-α and EGFR plays an important role in the prognosis of gastric carcinoma. This work was supported by the Marmara University Research Committee     

Progesterone effects on preterm birth in high-risk pregnancies: a randomized placebo-controlled trial

Purpose  

The purpose of this study was to evaluate whether the prophylactic administration of vaginal progesterone would reduce the preterm birth rate in high-risk population including singleton and twin pregnancies.