ApoB siRNA-induced Liver Steatosis is Resistant to Clearance by the Loss of Fatty Acid Transport Protein 5 (Fatp5)

The association between hypercholesterolemia and elevated serum apolipoprotein B (APOB) has generated interest in APOB as a therapeutic target for patients at risk of developing cardiovascular disease. In the clinic, mipomersen, an antisense oligonucleotide (ASO) APOB inhibitor, was associated with a trend toward increased hepatic triglycerides, and liver steatosis remains a concern. We found that siRNA-mediated knockdown of ApoB led to elevated hepatic triglycerides and liver steatosis in mice engineered to exhibit a human-like lipid profile. Many genes required for fatty acid synthesis were reduced, suggesting that the observed elevation in hepatic triglycerides is maintained by the cell through fatty acid uptake as opposed to fatty acid synthesis. Fatty acid transport protein 5 (Fatp5/Slc27a5) is required for long chain fatty acid (LCFA) uptake and bile acid reconjugation by the liver. Fatp5 knockout mice exhibited lower levels of hepatic triglycerides due to decreased fatty acid uptake, and shRNA-mediated knockdown of Fatp5 protected mice from diet-induced liver steatosis. Here, we evaluated if siRNA-mediated knockdown of Fatp5 was sufficient to alleviate ApoB knockdown-induced steatosis. We determined that, although Fatp5 siRNA treatment was sufficient to increase the proportion of unconjugated bile acids 100-fold, consistent with FATP5's role in bile acid reconjugation, Fatp5 knockdown failed to influence the degree, zonal distribution, or composition of the hepatic triglycerides that accumulated following ApoB siRNA treatment

The SERVICE Framework: A Public-service-dominant Approach to Sustainable Public Services

In this paper we argue that the new public management has been a flawed paradigm for public services delivery that has produced very internally efficient but externally ineffective public service organizations. Subsequently we develop the SERVICE framework for sustainable public services and public service organizations. This framework is rooted within the public‐service‐dominant business logic and emphasizes the need for a focus on external value creation rather than internal efficiency alone

Carotid Plaque Imaging with SPECT/CT and PET/CT

A major contributor to the occurrence of ischemic stroke is the existence of carotid atherosclerosis. A vulnerable carotid atherosclerotic plaque may rupture or erode, thus causing a thrombotic event. Currently, clinical decision-making with regard to carotid endarterectomy or stenting is still primarily based on the extent of luminal stenosis, estimated with CT angiography and/or (duplex) ultrasonography. However, there is growing evidence that the anatomic impact of stenosis alone has limited value in predicting the exact consequences of plaque vulnerability. Various molecular processes have, independently of degree of stenosis, shown to be importantly associated with the plaque's capability to cause thrombotic events. These molecular processes can be visualized with nuclear medicine techniques allowing the identification of vulnerable patients by non-invasive in vivo SPECT(/CT) and PET(/CT) imaging. This chapter provides an overview of SPECT(/CT) and PET(/CT) imaging with specific radiotracers that have been evaluated for the detection of plaques together with a future perspective in this field of imaging.</p

Crosstalk between reactive oxygen species and pro-inflammatory markers in developing various chronic diseases: a review

The inflammation process in the human body plays a central role in the pathogenesis of many chronic diseases. In addition, reactive oxygen species (ROS) exert potentially a decisive role in human body, particularly in physiological and pathological process. The chronic inflammation state could generate several types of diseases such as cancer, atherosclerosis, diabetes mellitus and arthritis, especially if it is concomitant with high levels of pro-inflammatory markers and ROS. The respiratory burst of inflammatory cells during inflammation increases the production and accumulation of ROS. However, ROS regulate various types of kinases and transcription factors such nuclear factor-kappa B which is related to the activation of pro-inflammatory genes. The exact crosstalk between pro-inflammatory markers and ROS in terms of pathogenesis and development of serious diseases is still ambitious. Many studies have been attempting to determine the mechanistic mutual relationship between ROS and pro-inflammatory markers. Therefore hereby, we review the hypothetical relationship between ROS and pro-inflammatory markers in which they have been proposed to initiate cancer, atherosclerosis, diabetes mellitus and arthritis

Interpersonal practice in project marketing: How institutional logics condition and change them: .

International audiencePurpose – Project marketing is the specific activity of companies selling projects-to-order. Interpersonal practice is known to be important in this type of marketing. While this interpersonal practice has been little studied, some previous research suggests that changes in the institutional macro environment have affected it. Therefore, the aim of this research is to study today’s interpersonal practice in project business, and how the institutional environment conditions it.Design/methodology/approach – Semi-structured interviews were conducted with marketing managers at project-based firms in different business sectors in France and Sweden. Grounded theory was followed during the analysis.Findings - The paper identifies three types of interpersonal practice in project marketing, referred to as the transactional, the work-based, and the socializing. Changes in these practices are explained in relation to the three institutional logics identified in the data: the market institutional logic of business ethics, the corporate institutional logic of rationalization, and the family institutional logic of gender equality. Research limitations/implications - Future studies can also continue and broaden this work as regards how the institutional conditioning of interpersonal practice varies with context.Practical implications – By clearly categorizing the three types of interpersonal practice and their relative role today, companies can orient the activities of salespeople, business developers and other project marketers. Originality/value – The paper contributes to the current debate on project marketing by identifying three types of interpersonal practice, and by illustrating how institutional logics condition and change these. The paper shows that extra-business activities are needed less than previous research has argued as regards maintaining customer relationships in-between projects

Continuity and change: the role of the HR function in the modern public sector

As the public sector has modernized and sought to become more efficient and cost-effective, the effective and strategic management of people has received increasing prominence and there have been calls for the Human Resource (HR) function to play a more strategic role. However, not much is known about whether the role of the HR function has changed substantively. In this paper, we present empirical evidence from six matched-pair public sector organizations in the UK to assess whether HR functional roles have changed, as envisaged, into a model more akin to the private sector. The findings highlight the complex and often contradictory nature of HR functional roles, and suggest that new and more strategic roles have not replaced traditional approaches but, rather, have been grafted on, giving rise to a variety of hybrid HR forms