Extracellular Sulfatases, Elements of the Wnt Signaling Pathway, Positively Regulate Growth and Tumorigenicity of Human Pancreatic Cancer Cells

BACKGROUND: Heparan sulfate proteoglycans (HSPGs) are control elements in Wnt signaling, which bind extracellularly to Wnt ligands and regulate their ability to interact with signal transduction receptors on the cell surface. Sulf-1 and Sulf-2 are novel extracellular sulfatases that act on internal glucosamine-6-sulfate (6S) modifications within HSPGs and thereby modulate HSPG interactions with various signaling molecules, including Wnt ligands. Emerging evidence indicates the importance of reactivated Wnt signaling in a number of cancers, including pancreatic adenocarcinoma. PRINCIPLE FINDINGS: Both Sulf proteins were upregulated in human pancreatic adenocarcinoma tumors and were broadly expressed in human pancreatic adenocarcinoma cell lines. Expression of human extracellular sulfatases Sulf-1 and Sulf-2 enhanced Wnt signaling in a reconstituted system. Three of four pancreatic adenocarcinoma cell lines tested exhibited autocrine Wnt signaling, in that extracellular Wnt ligands were required to initiate downstream Wnt signaling. Exposure of these pancreatic adenocarcinoma cells to a catalytically inactive form of Sulf-2 or siRNA-mediated silencing of endogenous Sulf-2 inhibited both Wnt signaling and cell growth. Sulf-2 silencing in two of these lines resulted in markedly reduced tumorigenesis in immunocompromised mice. CONCLUSIONS/SIGNIFICANCE: We have identified the Sulfs as potentiators of autocrine Wnt signaling in pancreatic cancer cells and have demonstrated their contribution to the growth and tumorigenicity of these cells. Since the Sulfs are extracellular enzymes, they would be attractive targets for therapy of pancreatic cancer. Our results run counter to the prevailing view in the literature that the Sulfs are negative regulators of tumorigenesis

Act In case of Depression: The evaluation of a care program to improve the detection and treatment of depression in nursing homes. Study Protocol

Contains fulltext : 95616.pdf (publisher's version ) (Open Access)BACKGROUND: The aim of this study is evaluating the (cost-) effectiveness of a multidisciplinary, evidence based care program to improve the management of depression in nursing home residents of somatic and dementia special care units. The care program is an evidence based standardization of the management of depression, including standardized use of measurement instruments and diagnostical methods, and protocolized psychosocial, psychological and pharmacological treatment. METHODS/DESIGN: In a 19-month longitudinal controlled study using a stepped wedge design, 14 somatic and 14 dementia special care units will implement the care program. All residents who give informed consent on the participating units will be included. Primary outcomes are the frequency of depression on the units and quality of life of residents on the units. The effect of the care program will be estimated using multilevel regression analysis. Secondary outcomes include accuracy of depression-detection in usual care, prevalence of depression-diagnosis in the intervention group, and response to treatment of depressed residents. An economic evaluation from a health care perspective will also be carried out. DISCUSSION: The care program is expected to be effective in reducing the frequency of depression and in increasing the quality of life of residents. The study will further provide insight in the cost-effectiveness of the care program. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR1477

The CARTS study: Chemoradiation therapy for rectal cancer in the distal rectum followed by organ-sparing transanal endoscopic microsurgery

Contains fulltext : 96401.pdf (publisher's version ) (Open Access

General practitioners' patient-centredness and responses to patients' emotional cues and concerns: relationships with perceived empathy in areas of high and low socioeconomic deprivation

<b>Background</b> Physician empathy is important to patients across the socio-economic spectrum. However, whether socioeconomic status (SES) influences how patients’ judge physician empathy is not known. We investigated how patients’ perceptions of their general practitioners’ (GPs) empathy related to objectively measured patient-centeredness of the GPs and their detection and response to emotional cues.<p></p> <b>Methods</b> Secondary analysis of 112 videoed consultations of 8 GPs with the high and low empathy scores as rated by patients using the Consultation and Relational Empathy (CARE) Measure working in high or low deprivation settings in Scotland. Objective assessment involved the Measure of Patient-Centredness (MPCC) which has 3 components (exploring disease and illness experience, understanding the whole person, and finding common ground) and the Verona coding system (which measures emotional cues, concerns and responses).<p></p> <b>Results</b> GPs rated by patients as being empathic were more patient-centred overall than those rated as less empathic, in both high (p = 0.03) and low deprivation areas (p = 0.05). In high deprivation areas, perceived empathy was related to finding common ground (p = 0.02) whereas in low deprivation areas it was related to understanding the whole person (p= 0.01). In high deprivation areas, empathic GPs also had significantly different responses to emotional cues and concerns than GPs perceived as having low empathy.<p></p> <b>Conclusion</b> Socioeconomic status appears to affect how patients judge practitioner empathy. This study emphasises the importance of finding common ground and detecting and responding actively to emotional cues in consultations in high deprivation areas. Further research on a larger sample is warranted

Appointments: a more effective commitment device for health behaviours

Health behaviors are plagued by self-control problems, and commitment devices are frequently proposed as a solution. We show that a simple alternative works even better: appointments. We randomly offer HIV testing appointments and financial com¬mitment devices to high-risk men in Malawi. Appointments are much more effective than financial commitment devices, more than doubling testing rates. In contrast, most men who take up financial commitment devices lose their investments. Appointments address procrastination without the potential drawback of commitment failure, and also address limited memory problems. Appointments have the potential to increase demand for healthcare in the developing world