Physician burnout : a "meta-o-scopic" analysis

xi, 104 leaves : ill. ; 29 cmThis study investigates the contradictions that exist within the physician burnout literature. Through the use of meta-analysis, physician burnout and its relationships to gender, medical specialty, age, illness, and satisfaction were analyzed. The results indicate that female physicians are more emotionally exhausted than male physicians and depersonalization is higher among male than female physicians. General practitioners report higher levels of emotional exhaustion than any other medical specialty. A low to moderate negative correlation exists between physician age and burnout, a moderate to substantial positive correlation exists between burnout and physician illness, and a moderate to substantial negative correlation exists between burnout and physician satisfaction. The results of this project heighten our awareness of the risks associated with being a physician, as well as extend a call to action so that effective and preventative measures can be implemented

Autophagy in Multiple Sclerosis:Two Sides of the Same Coin

Multiple sclerosis (MS) is a complex auto-immune disorder of the central nervous system (CNS) that involves a range of CNS and immune cells. MS is characterized by chronic neuroinflammation, demyelination, and neuronal loss, but the molecular causes of this disease remain poorly understood. One cellular process that could provide insight into MS pathophysiology and also be a possible therapeutic avenue, is autophagy. Autophagy is an intracellular degradative pathway essential to maintain cellular homeostasis, particularly in neurons as defects in autophagy lead to neurodegeneration. One of the functions of autophagy is to maintain cellular homeostasis by eliminating defective or superfluous proteins, complexes, and organelles, preventing the accumulation of potentially cytotoxic damage. Importantly, there is also an intimate and intricate interplay between autophagy and multiple aspects of both innate and adaptive immunity. Thus, autophagy is implicated in two of the main hallmarks of MS, neurodegeneration, and inflammation, making it especially important to understand how this pathway contributes to MS manifestation and progression. This review summarizes the current knowledge about autophagy in MS, in particular how it contributes to our understanding of MS pathology and its potential as a novel therapeutic target

WDR45, one gene associated with multiple neurodevelopmental disorders

The WDR45 gene is localized on the X-chromosome and variants in this gene are linked to six different neurodegenerative disorders, i.e., ss-propeller protein associated neurodegeneration, Rett-like syndrome, intellectual disability, and epileptic encephalopathies including developmental and epileptic encephalopathy, early-onset epileptic encephalopathy and West syndrome and potentially also specific malignancies. WDR45/WIPI4 is a WD-repeat beta-propeller protein that belongs to the WIPI (WD repeat domain, phosphoinositide interacting) family. The precise cellular function of WDR45 is still largely unknown, but deletions or conventional variants in WDR45 can lead to macroautophagy/autophagy defects, malfunctioning mitochondria, endoplasmic reticulum stress and unbalanced iron homeostasis, suggesting that this protein functions in one or more pathways regulating directly or indirectly those processes. As a result, the underlying cause of the WDR45-associated disorders remains unknown. In this review, we summarize the current knowledge about the cellular and physiological functions of WDR45 and highlight how genetic variants in its encoding gene may contribute to the pathophysiology of the associated diseases. In particular, we connect clinical manifestations of the disorders with their potential cellular origin of malfunctioning and critically discuss whether it is possible that one of the most prominent shared features, i.e., brain iron accumulation, is the primary cause for those disorders

Multimedia delivery in the future internet

The term “Networked Media” implies that all kinds of media including text, image, 3D graphics, audio and video are produced, distributed, shared, managed and consumed on-line through various networks, like the Internet, Fiber, WiFi, WiMAX, GPRS, 3G and so on, in a convergent manner [1]. This white paper is the contribution of the Media Delivery Platform (MDP) cluster and aims to cover the Networked challenges of the Networked Media in the transition to the Future of the Internet. Internet has evolved and changed the way we work and live. End users of the Internet have been confronted with a bewildering range of media, services and applications and of technological innovations concerning media formats, wireless networks, terminal types and capabilities. And there is little evidence that the pace of this innovation is slowing. Today, over one billion of users access the Internet on regular basis, more than 100 million users have downloaded at least one (multi)media file and over 47 millions of them do so regularly, searching in more than 160 Exabytes1 of content. In the near future these numbers are expected to exponentially rise. It is expected that the Internet content will be increased by at least a factor of 6, rising to more than 990 Exabytes before 2012, fuelled mainly by the users themselves. Moreover, it is envisaged that in a near- to mid-term future, the Internet will provide the means to share and distribute (new) multimedia content and services with superior quality and striking flexibility, in a trusted and personalized way, improving citizens’ quality of life, working conditions, edutainment and safety. In this evolving environment, new transport protocols, new multimedia encoding schemes, cross-layer inthe network adaptation, machine-to-machine communication (including RFIDs), rich 3D content as well as community networks and the use of peer-to-peer (P2P) overlays are expected to generate new models of interaction and cooperation, and be able to support enhanced perceived quality-of-experience (PQoE) and innovative applications “on the move”, like virtual collaboration environments, personalised services/ media, virtual sport groups, on-line gaming, edutainment. In this context, the interaction with content combined with interactive/multimedia search capabilities across distributed repositories, opportunistic P2P networks and the dynamic adaptation to the characteristics of diverse mobile terminals are expected to contribute towards such a vision. Based on work that has taken place in a number of EC co-funded projects, in Framework Program 6 (FP6) and Framework Program 7 (FP7), a group of experts and technology visionaries have voluntarily contributed in this white paper aiming to describe the status, the state-of-the art, the challenges and the way ahead in the area of Content Aware media delivery platforms

Cell transformation assays for prediction of carcinogenic potential: State of the science and future research needs

Copyright @ 2011 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.Cell transformation assays (CTAs) have long been proposed as in vitro methods for the identification of potential chemical carcinogens. Despite showing good correlation with rodent bioassay data, concerns over the subjective nature of using morphological criteria for identifying transformed cells and a lack of understanding of the mechanistic basis of the assays has limited their acceptance for regulatory purposes. However, recent drivers to find alternative carcinogenicity assessment methodologies, such as the Seventh Amendment to the EU Cosmetics Directive, have fuelled renewed interest in CTAs. Research is currently ongoing to improve the objectivity of the assays, reveal the underlying molecular changes leading to transformation and explore the use of novel cell types. The UK NC3Rs held an international workshop in November 2010 to review the current state of the art in this field and provide directions for future research. This paper outlines the key points highlighted at this meeting

Human mass balance study of the novel anticancer agent ixabepilone using accelerator mass spectrometry

Ixabepilone (BMS-247550) is a semi-synthetic, microtubule stabilizing epothilone B analogue which is more potent than taxanes and has displayed activity in taxane-resistant patients. The human plasma pharmacokinetics of ixabepilone have been described. However, the excretory pathways and contribution of metabolism to ixabepilone elimination have not been determined. To investigate the elimination pathways of ixabepilone we initiated a mass balance study in cancer patients. Due to autoradiolysis, ixabepilone proved to be very unstable when labeled with conventional [14C]-levels (100 μCi in a typical human radio-tracer study). This necessitated the use of much lower levels of [14C]-labeling and an ultra-sensitive detection method, Accelerator Mass Spectrometry (AMS). Eight patients with advanced cancer (3 males, 5 females; median age 54.5 y; performance status 0–2) received an intravenous dose of 70 mg, 80 nCi of [14C]ixabepilone over 3 h. Plasma, urine and faeces were collected up to 7 days after administration and total radioactivity (TRA) was determined using AMS. Ixabepilone in plasma and urine was quantitated using a validated LC-MS/MS method. Mean recovery of ixabepilone-derived radioactivity was 77.3% of dose. Fecal excretion was 52.2% and urinary excretion was 25.1%. Only a minor part of TRA is accounted for by unchanged ixabepilone in both plasma and urine, which indicates that metabolism is a major elimination mechanism for this drug. Future studies should focus on structural elucidation of ixabepilone metabolites and characterization of their activities

Transcriptional and epigenetic profiling of nutrient-deprived cells to identify novel regulators of autophagy

Macroautophagy (hereafter autophagy) is a lysosomal degradation pathway critical for maintaining cellular homeostasis and viability, and is predominantly regarded as a rapid and dynamic cytoplasmic process. To increase our understanding of the transcriptional and epigenetic events associated with autophagy, we performed extensive genome-wide transcriptomic and epigenomic profiling after nutrient deprivation in human autophagy-proficient and autophagy-deficient cells. We observed that nutrient deprivation leads to the transcriptional induction of numerous autophagy-associated genes. These transcriptional changes are reflected at the epigenetic level (H3K4me3, H3K27ac, and H3K56ac) and are independent of autophagic flux. As a proof of principle that this resource can be used to identify novel autophagy regulators, we followed up on one identified target: EGR1 (early growth response 1), which indeed appears to be a central transcriptional regulator of autophagy by affecting autophagy-associated gene expression and autophagic flux. Taken together, these data stress the relevance of transcriptional and epigenetic regulation of autophagy and can be used as a resource to identify (novel) factors involved in autophagy regulation