Relevance of mitogen activated protein kinase (MAPK) and phosphotidylinositol-3-kinase/protein kinase B (PI3K/PKB) pathways to induction of apoptosis by curcumin in breast cells

Following observations that curcumin inhibited proliferation (IC(50)=1-5 microM), invasiveness and progression through S/G2/M phases of the cell cycle in the non-tumourigenic HBL100 and tumourigenic MDA-MB-468 human breast cell lines, it was noted that apoptosis was much more pronounced in the tumour line. Therefore, the ability of curcumin to modulate signalling pathways which might contribute to cell survival was investigated. After pre-treatment of cells for 20 min, curcumin (40 microM) inhibited EGF-stimulated phosphorylation of the EGFR in MDA-MB-468 cells and phosphorylation of extracellular signal regulated kinases (ERKs) 1 and 2, as well as ERK activity and levels of nuclear c-fos in both cell lines. At a lower dose (10 microM), it also inhibited the ability of anisomycin to activate JNK, resulting in decreased c-jun phosphorylation, although it did not inhibit JNK activity directly. In contrast, the activation of p38 mitogen activated protein kinase (MAPK) by anisomycin was not inhibited. Curcumin inhibited basal phosphorylation of Akt/protein kinase B (PKB) in both cell lines, but more consistently and to a greater extent in the MDA-MB-468 cells. The MAPK kinase (MKK) inhibitor U0126 (10 microM), while preventing ERK phosphorylation in MDA-MB-468 cells, did not induce apoptosis. The PI3K inhibitor LY294002 (50 microM) inhibited PKB phosphorylation in both cells lines, but only induced apoptosis in the MDA-MB-468 line. These results suggest that while curcumin has several different molecular targets within the MAPK and PI3K/PKB signalling pathways that could contribute to inhibition of proliferation and induction of apoptosis, inhibition of basal activity of Akt/PKB, but not ERK, may facilitate apoptosis in the tumour cell line.     

International perspectives on patient engagement: results from the 2011 Commonwealth Fund Survey

We analyzed 2011 survey data of patients with complex health care needs in 11 countries (Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, the United Kingdom, and the United States) on their care experiences. Wide country variation was reported in how well patients were engaged by their clinicians; UK and Swiss patients reported the most positive experiences, but gaps were reported in all countries. Disparities by income were found in several countries, with the widest gaps reported in the United States. Across countries, engaged patients reported receiving higher-quality care, fewer errors, and more positive views of the health system.     

Psychophysical measures of central auditory dysfunction in multiple sclerosis: neurophysiological and neuroanatomical correlates

Central auditory function was assessed in 15 patients with multiple sclerosis (MS) to determine whether the demyelinating lesions resulted in disruption of temporal processing. Auditory evoked potential (AEP) recordings included all three latency regions: Auditory brain stem responses (ABRs), midlatency responses (MLRs), and long-latency responses (LLRs). Two psychophysical tasks thought to involve temporal processing were used: a monaural-processing task (gap-detection) and a binaural-processing task (masking level difference; MLD). Further, AEP abnormalities and psychophysical performance deficits were related to lesion location, based on magnetic resonance imaging (MRI) scans. Reduced MLDs were seen in six MS subjects. Abnormal MLDs were always accompanied by abnormal ABRs and MLRs, and compared to subjects with normal MLDs, the subjects with abnormal MLDs were more likely to have bilateral abnormalities in the AEPs. Further, MLR indices of abnormal binaural interaction appeared to be specifically related to the psychophysical measure of binaural processing. The MRI data of these patients indicated widespread involvement of the auditory pathway. MS subjects with abnormal MRI signals restricted to levels caudal to the lateral lemniscus did not have abnormal MLDs. Gap-detection thresholds were more resistant to the effects of the demyelinating lesions; only two subjects had abnormal gap-detection thresholds. These subjects had extensive AEP abnormalities (bilaterally, in all three latency regions). The gap-detection thresholds were most specifically related to abnormalities of the LLRs. In addition, the subjects with elevated gap-detection thresholds were the only ones with a prolonged interval between the ABRs and MLRs. Thus, efficient neural conduction between the upper brain stem and auditory cortex appears to be crucial for normal monaural temporal processing. The results indicate that demyelinating lesions can cause deficits in temporal processing in the central auditory pathway. However, auditory temporal processing is not a unitary phenomenon since abnormalities at different levels of the auditory system disrupt different types of temporal processing. Finally, abnormal psychophysical performance was not seen in all subjects with AEP and MRI evidence of involvement of the auditory pathway; rather, these psychophysical measures appeared to be sensitive to disruption only in specific portions of the auditory system.     

Development and assessment of the Alberta Context Tool

Background  

The context of healthcare organizations such as hospitals is increasingly accepted as having the potential to influence the use of new knowledge. However, the mechanisms by which the organizational context influences evidence-based practices are not well understood. Current measures of organizational context lack a theory-informed approach, lack construct clarity and generally have modest psychometric properties. This paper presents the development and initial psychometric validation of the Alberta Context Tool (ACT), an eight dimension measure of organizational context for healthcare settings.     

Mediastinal tumors: biopsy under US guidance

Percutaneous biopsies of mediastinal tumors were successfully performed under sonographic guidance in 14 of 21 patients. In 10 of 11 malignant lesions, malignancy was determined by means of cytologic and histologic examination of the specimens obtained. A histologic diagnosis was reached in seven patients with malignant mediastinal tumors, including all four cases of Hodgkin lymphoma. Mediastinal biopsy under sonographic guidance is a technically simple, rapid, and accurate procedure, but its application is limited to tumors of the anterior mediastinum.