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Key enzymes of cholesterol metabolism were studied in two inbred strains of rabbits with hyper- or hyporesponse of serum cholesterol to dietary cholesterol. Baseline 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity in liver was similar in hypo- and hyperresponders, but that in intestine was twofold higher in the hyporesponders. The addition of cholesterol (3 g/kg) to the diet caused similar depression of hepatic HMG-CoA reductase activity in the two strains, whereas intestinal HMG-CoA reductase activity was significantly reduced in hyporesponders but not in hyperresponders. Cholesterol feeding induced higher free cholesterol concentrations in hepatic and intestinal microsomes of both hypo- and hyperresponders and higher activity of hepatic acyl-CoA:cholesterol acyltransferase (ACAT). Hepatic ACAT activity was significantly lower in cholesterol-fed hyperresponders than in hyporesponders, which may have contributed to the observed higher free cholesterol concentrations in hepatic microsomes of cholesterol-fed hyperresponders. Intestinal ACAT activity was similar in hypo- and hyperresponders; cholesterol feeding tended (P = 0.11) to elevate the activity of this enzyme. Hepatic cholesterol 7-alpha-hydroxylase activity was significantly higher in cholesterol-fed hyperresponders than in hyporesponders; it was slightly depressed after cholesterol loading in both rabbit strains. J. Nutr. 123: 695-703, 1993.

Pells (2021) then answers that he thinks the purpose of project management should be to advance positive change in the world and he further states that it should be about more than making money, developing models and standards, or even educating project managers. Pells (2021) states that perhaps the most significant thing that he has realised this year is the overwhelming importance of programmes and projects coming first before project management (perhaps). Pells (2012) clarifies that projects, outcomes,and benefits matter more to most stakeholders than project management methods, processes, standards,knowledge, experience,and leadership. Pells (2012) concludes Part 1 of his editorial of four parts with the following statement: “I think project management needs a higher purpose”. As a semi-retired organisational project management practitioner, I tend to agree with the editorials by Pells (2021 and 2021a) and with the recent articles and letters that responded to the first editorial published in January (e.g., Abuya, Young, Minelle, da Silva Neto, and Stretton(2021)). When I had to retire from my permanent job when I reached the age of 65 at the end of 2018, I decided that I would like to reflect on my career as an organisational project management practitioner and published some opinion articles which I have done (Smit, 2019 & 2020). Last year I wanted to write a short article to share my opinion on what I think the calling of organisational project management practitioners is. I have not done so as my wife and I are really enjoying our retirement by travelling and enjoying the beautiful Southern African nature (of course within the regulations of Covid-19). The editorials by Pells (2021 and 2012a) have now inspired me to write this article and share my opinion on the question: “Do organisational project management practitioners have a higher calling/purpose in life?”.In this article Ialso share a high-level a portfolio management model that organisational project management practitioners can apply to execute organisational strategies in order to deliver sustainable business value for organisations. [ABSTRACT FROM AUTHOR]

The author is now in a new phase of his life after he had to exit employment with his employer when he reached the age of 65. It is thus an opportune time for the author to do some reflection after having had the privilege to gain excellent experience in organisational project management during a working career of some 45 years. The author obtained his PMP® in 1992 (#1071). At that time the PMBOK® Guide (i.e. A Guide to the Project Management Body of Knowledge) had eight Project Management Knowledge Areas (Project Integration Management and Project Stakeholder Management were added later). In this opinion piece the author suggests that the Project Management Institute (PMI) Development and Review Team for the PMBOK® Guide- Seventh Edition should consider the possible inclusion of additional Project Management Knowledge Areas with their associated project management processes. [ABSTRACT FROM AUTHOR]

This research study is a normative case study to develop a portfolio management model for a State Owned Enterprise in South Africa to effectively implement and embed portfolio management best practices. The implementation of the recommendations resulting from this research will improve the maturity of portfolio management processes and contribute towards the State Owned Enterprise becoming a high agile organisation by ensuring that projects and programmes align to the strategic objectives to deliver the required strategic results. The research study also expands the theory/body of knowledge on portfolio management models and the steps to be followed to successfully implement and embed portfolio management best practices. The portfolio management model and the implementation steps can be used by other organisations as a blueprint for implementing portfolio management best practices. [ABSTRACT FROM AUTHOR]

The ATP-binding cassette transporter ABCA1 is essential for high density lipoprotein (HDL) formation and considered rate-controlling for reverse cholesterol transport. Expression of the Abca1 gene is under control of the liver X receptor (LXR). We have evaluated effects of LXR activation by the synthetic agonist T0901317 on hepatic and intestinal cholesterol metabolism in C57BL/6J and DBA/1 wild-type mice and in ABCA1-deficient DBA/1 mice. In wild-type mice, T0901317 increased expression of Abca1 in liver and intestine, which was associated with an approximately 60% rise in HDL. Biliary cholesterol excretion rose 2.7-fold upon treatment, and fecal neutral sterol output was increased by 150-300%. Plasma cholesterol levels also increased in treated Abca1(-/-) mice (+120%), but exclusively in very low density lipoprotein-sized fractions. Despite the absence of HDL, hepatobiliary cholesterol output was stimulated upon LXR activation in Abca1(-/-) mice, leading to a 250% increase in the biliary cholesterol/phospholipid ratio. Most importantly, fecal neutral sterol loss was induced to a similar extent (+300%) by the LXR agonist in DBA/1 wild-type and Abca1(-/-) mice. Expression of Abcg5 and Abcg8, recently implicated in biliary excretion of cholesterol and its intestinal absorption, was induced in T0901317-treated mice. Thus, activation of LXR in mice leads to enhanced hepatobiliary cholesterol secretion and fecal neutral sterol loss independent of (ABCA1-mediated) elevation of HDL and the presence of ABCA1 in liver and intestine.