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Klil-Drori A.J.,Rambam Health Care Campus
Prostaglandins & other lipid mediators | Year: 2013

Among the lipoxygenases, a diverse family of fatty acid dioxygenases with varying tissue-specific expression, 15-lipoxygenase (15-LOX) was found to be involved in many aspects of human cancer, such as angiogenesis, chronic inflammation, metastasis formation, and direct and indirect tumor suppression. Herein, evidence for the expression and action of 15-LOX and its orthologs in various neoplasms, including solid tumors and hematologic malignancies, is reviewed. The debate surrounding the impact of 15-LOX as either a tumor-promoting or a tumor-suppressing enzyme is highlighted and discussed in the context of its role in other biological systems. Copyright © 2013 Elsevier Inc. All rights reserved. Source


Skorecki K.L.,Technion - Israel Institute of Technology | Wasser W.G.,Rambam Health Care Campus
Kidney International | Year: 2013

Lipkowitz et al. extend the African American Study of Kidney Disease and Hypertension to the level of genetic epidemiology, in a case-control study design. Analysis of genotypes at the APOL1 kidney disease risk region supports a paradigm shift in which genetic risk is proximate to both kidney disease and hypertension. The findings mandate urgency in clarifying mechanisms whereby APOL1 region risk variants interact with environmental triggers to cause progressive kidney disease accompanied by dangerous hypertension. © 2012 International Society of Nephrology. Source


Greer I.A.,University of Liverpool | Brenner B.,Rambam Health Care Campus | Gris J.-C.,University of Nimes
British Journal of Haematology | Year: 2014

Haemostatic and vascular biology mechanisms appear to play an important role in the pathogenesis of placenta-mediated pregnancy complications. Although low-dose aspirin (LDA) has a modest effect in preventing preeclampsia, antithrombotic interventions, LDA and low molecular weight heparin (LMWH) have not definitively proven their effectiveness in women with placenta-mediated pregnancy complications selected by previous pregnancy outcome alone. Given the heterogeneous aetiology of placenta-mediated pregnancy complications, it is critical to stratify patients according to maternal and fetal characteristics and disease mechanisms rather than simply by pregnancy outcome, such as miscarriage. Such stratification could identify those who could benefit from antithrombotic interventions in pregnancy. We lack data on genome-wide association studies, biomarkers and trials of interventions applied to specific homogeneous populations. Future studies should focus on elaborating different disease mechanisms and examining antithrombotic interventions in specific and more homogeneous groups, such as thrombophilic women with well-characterized placenta-mediated pregnancy complications, stratified by disease severity and pathological findings. Because of fetal safety concerns with new anticoagulants, the intervention should focus on heparins alone or in combination with LDA. Thus, placenta-mediated pregnancy complications deserve precision medicine, defining disease by mechanism rather than outcome with interventions focused on a more personalized approach. © 2014 John Wiley & Sons Ltd. Source


Kaidar-Person O.,Rambam Health Care Campus | Roach III M.,University of California at San Francisco | Crehange G.,Georges Francois Leclerc Cancer Center
International Journal of Radiation Oncology Biology Physics | Year: 2013

Given the low α/β ratio of prostate cancer, prostate hypofractionation has been tested through numerous clinical studies. There is a growing body of literature suggesting that with high conformal radiation therapy and even with more sophisticated radiation techniques, such as high-dose-rate brachytherapy or image-guided intensity modulated radiation therapy, morbidity associated with shortening overall treatment time with higher doses per fraction remains low when compared with protracted conventional radiation therapy to the prostate only. In high-risk prostate cancer patients, there is accumulating evidence that either dose escalation to the prostate or hypofractionation may improve outcome. Nevertheless, selected patients who have a high risk of lymph node involvement may benefit from whole-pelvic radiation therapy (WPRT). Although combining WPRT with hypofractionated prostate radiation therapy is feasible, it remains investigational. By combining modern advances in radiation oncology (high-dose-rate prostate brachytherapy, intensity modulated radiation therapy with an improved image guidance for soft-tissue sparing), it is hypothesized that WPRT could take advantage of recent results from hypofractionation trials. Moreover, the results from hypofractionation trials raise questions as to whether hypofractionation to pelvic lymph nodes with a high risk of occult involvement might improve the outcomes in WPRT. Although investigational, this review discusses the challenging idea of WPRT in the context of hypofractionation for patients with high-risk prostate cancer. © 2013 Elsevier Inc. Source


Shahaf G.,Rambam Health Care Campus | Pratt H.,Technion - Israel Institute of Technology
Frontiers in Human Neuroscience | Year: 2013

In this work we demonstrate the principles of a systematic modeling approach of the neurophysiologic processes underlying a behavioral function. The modeling is based upon a flexible simulation tool, which enables parametric specification of the underlying neurophysiologic characteristics. While the impact of selecting specific parameters is of interest, in this work we focus on the insights, which emerge from rather accepted assumptions regarding neuronal representation. We show that harnessing of even such simple assumptions enables the derivation of significant insights regarding the nature of the neurophysiologic processes underlying behavior. We demonstrate our approach in some detail by modeling the behavioral go/no-go task. We further demonstrate the practical significance of this simplified modeling approach in interpreting experimental data - the manifestation of these processes in the EEG and ERP literature of normal and abnormal (ADHD) function, as well as with comprehensive relevant ERP data analysis. In-fact we show that from the modelbased spatiotemporal segregation of the processes, it is possible to derive simple and yet effective and theory-based EEG markers differentiating normal and ADHD subjects. We summarize by claiming that the neurophysiologic processes modeled for the go/no-go task are part of a limited set of neurophysiologic processes which underlie, in a variety of combinations, any behavioral function with measurable operational definition. Such neurophysiologic processes could be sampled directly from EEG on the basis of model-based spatiotemporal segregation. © 2013 Shahaf and Pratt. Source

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