Antidepressants induce cellular insulin resistance by activation of IRS-1 kinases

Certain selective serotonin reuptake inhibitors (SSRIs) induce the clinical and biochemical manifestations of a metabolic syndrome by as yet unknown mechanism. Here we demonstrate that incubation (1 h) of rat hepatoma Fao cells with the SSRIs paroxetine and sertraline, but not with the atypical antipsychotic drug olanzapine, inhibited the insulin-stimulated Tyr phosphorylation of the insulin receptor substrate-1 (IRS-1) with half-maximal effects at approximately 10 microM. This inhibition correlated with a rapid phosphorylation and activation of a number of Ser/Thr IRS-1 kinases including JNK, S6K1, ERK and p38 MAPK, but not PKB (Akt). JNK appears as a key player activated by SSRIs because specific JNK inhibitors partially eliminated the effects of these drugs. The SSRIs induced the phosphorylation of IRS-1 on S307 and S408, which inhibits IRS-1 function and insulin signaling. These results implicate selected SSRIs as inhibitors of insulin signaling and as potential inducers of cellular insulin resistance.     

Views on depression among patients diagnosed as depressed in a poor town on the outskirts of São Paulo, Brazil

Depression has important cultural and social components. Interviews with 16 women living in the poor and violent outskirts of S?o Paulo were analyzed to identify local concepts of depression. The interviews were conducted with women who were diagnosed with depression and patients in treatment at a primary care unit. For these women, depression was inextricably woven into their violent and downtrodden daily lives, as well as with other sources of suffering. The local community identified two types of depression: 'true' and 'false,' suggesting a concept enmeshed with morality.     

Biomechanics of the elbow joint in tennis players and relation to pathology

Elbow injuries constitute a sizeable percentage of tennis injuries. A basic understanding of biomechanics of tennis and analysis of the forces, loads and motions of the elbow during tennis will improve the understanding of the pathophysiology of these injuries. All different strokes in tennis have a different repetitive biomechanical nature that can result in tennis-related injuries. In this article, a biomechanically-based evaluation of tennis strokes is presented. This overview includes all tennis-related pathologies of the elbow joint, whereby the possible relation of biomechanics to pathology is analysed, followed by treatment recommendations.     

Interactive computer-aided diagnosis of breast masses: computerized selection of visually similar image sets from a reference library

RATIONALE AND OBJECTIVES: The clinical utility of interactive computer-aided diagnosis (ICAD) systems depends on clinical relevance and visual similarity between the queried breast lesions and the ICAD-selected reference regions. The objective of this study is to develop and test a new ICAD scheme that aims improve visual similarity of ICAD-selected reference regions. MATERIALS AND METHODS: A large and diverse reference library involving 3,000 regions of interests was established. For each queried breast mass lesion by the observer, the ICAD scheme segments the lesion, classifies its boundary spiculation level, and computes 14 image features representing the segmented lesion and its surrounding tissue background. A conditioned k-nearest neighbor algorithm is applied to select a set of the 25 most "similar" lesions from the reference library. After computing the mutual information between the queried lesion and each of these initially selected 25 lesions, the scheme displays the six reference lesions with the highest mutual information scores. To evaluate the automated selection process of the six "visually similar" lesions to the queried lesion, we conducted a two-alternative forced-choice observer preference study using 85 queried mass lesions. Two sets of reference lesions selected by one new automated ICAD scheme and the other previously reported scheme using a subjective rating method were randomly displayed on the left and right side of the queried lesion. Nine observers were asked to decide for each of the 85 queried lesions which one of the two reference sets was "more visually similar" to the queried lesion. RESULTS: In classification of mass boundary spiculation levels, the overall agreement rate between the automated scheme and an observer is 58.8% (Kappa = 0.31). In observer preference study, the nine observers preferred on average the reference lesion sets selected by the automated scheme as being more visually similar than the set selected by the subjective rating approach in 53.2% of the queried lesions. The results were not significantly different for the two methods (P = .128). CONCLUSIONS: This study suggests that using the new automated ICAD scheme, the interobserver variability related issues can thus be avoided. Furthermore, the new scheme maintains the similar performance level as the previous scheme using the subjective rating method that can select reference sets that are significantly more visually similar (P < .05) than when using traditional ICAD schemes in which the mass boundary spiculation levels are not accurately detected and quantified.     

Attenuation correction in cardiac PET/CT with three different CT protocols: a comparison with conventional PET

Purpose CT-based attenuation correction may influence cardiac PET owing to its higher susceptibility to misalignment compared with conventional ⁶⁸Ge transmission scans. The aims of this study were to evaluate whether CT attenuation correction leads to changes in tracer distribution compared with conventional cardiac PET and to determine a suitable CT protocol. Methods A total of 27 patients underwent PET/CT and subsequently a PET scan. Twenty patients received a low-dose CT (LDCT group; 120 kV, 26 mA, 8-s scan time), seven patients a slow CT (SCT group; 120 kV, 99 mA, 46-s scan time) and ten patients an ultra-low-dose CT (ULDCT group; 80 kV, 13 mA, 5-s scan time) as the transmission scan in PET/CT. Polar maps were divided into 17 segments and regression analysis was computed in every scan pair (CT attenuation corrected–⁶⁸Ge attenuation corrected). Correlation coefficient (r), the slope (s) and the offset (os) of the regression line were determined. Visual assessment of misalignment between the transmission and emission data was performed. The effective dose of the different transmission scans was calculated. Results Overall, there was a moderate correlation between the mean values measured in all segments on PET/CT and on PET when using LDCT (r=0.78, p<0.0001), SCT (r=0.79, p<0.0001) and ULDCT (r=0.82, p<0.0001). No differences were observed when comparing the scores assigned in the visual misalignment assessment in the three groups (p=0.12). The differences between the results from the regression analysis observed in the respective groups were not statistically significant (Kruskal-Wallis p=0.11 for r, p=0.67 for s and p=0.27 for os). The effective dose was lowest for the ULDCT. Conclusion Our study shows that CT-based attenuation correction is feasible for cardiac PET imaging. The results indicate that ultra-low-dose CT is the preferable choice for transmission scanning.