Co-Administration of Propionate or Protocatechuic Acid Does Not Affect DHA-Specific Transcriptional Effects on Lipid Metabolism in Cultured Hepatic Cells.

Long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) are collectively recognized triglyceride-lowering agents, and their preventive action is likely mediated by changes in gene expression. However, as most studies employ fish oil, which contains a mixture of n-3 LC-PUFAs, the docosahexaenoic acid (DHA)-specific transcriptional effects on lipid metabolism are still unclear. The aim of the present study was to further elucidate the DHA-induced transcriptional effects on lipid metabolism in the liver, and to investigate the effects of co-administration with other bioactive compounds having effects on lipid metabolism. To this purpose, HepG2 cells were treated for 6 or 24 h with DHA, the short-chain fatty acid propionate (PRO), and protocatechuic acid (PCA), the main human metabolite of cyanidin-glucosides. Following supplementation, we mapped the global transcriptional changes. PRO and PCA alone had a very slight effect on the transcriptome; on the contrary, supplementation of DHA highly repressed the steroid and fatty acid biosynthesis pathways, this transcriptional modulation being not affected by co-supplementation. Our results confirm that DHA effect on lipid metabolism are mediated at least in part by modulation of the expression of specific genes. PRO and PCA could contribute to counteracting dyslipidemia through other mechanisms.

Osteogenesis depends on commissioning of a network of stem cell transcription factors that act as repressors of adipogenesis.

Mesenchymal (stromal) stem cells (MSCs) constitute populations of mesodermal multipotent cells involved in tissue regeneration and homeostasis in many different organs. Here we performed comprehensive characterization of the transcriptional and epigenomic changes associated with osteoblast and adipocyte differentiation of human MSCs. We demonstrate that adipogenesis is driven by considerable remodeling of the chromatin landscape and de novo activation of enhancers, whereas osteogenesis involves activation of preestablished enhancers. Using machine learning algorithms for in silico modeling of transcriptional regulation, we identify a large and diverse transcriptional network of pro-osteogenic and antiadipogenic transcription factors. Intriguingly, binding motifs for these factors overlap with SNPs related to bone and fat formation in humans, and knockdown of single members of this network is sufficient to modulate differentiation in both directions, thus indicating that lineage determination is a delicate balance between the activities of many different transcription factors.

Author Correction: Osteogenesis depends on commissioning of a network of stem cell transcription factors that act as repressors of adipogenesis.

In the version of this article initially published, in the graph keys in Fig. 1i, the colors indicating 'Ob' and 'Ad' were red and blue, respectively, but should have been blue and red, respectively; the shapes indicating 'MUS' and 'BM' were a triangle and a square, respectively, but should have been a square and a triangle, respectively. The errors have been corrected in the HTML and PDF versions of the article.

Transcriptional regulation of Hepatic Stellate Cell activation in NASH.

Non-alcoholic steatohepatitis (NASH) signified by hepatic steatosis, inflammation, hepatocellular injury, and fibrosis is a growing cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma. Hepatic fibrosis resulting from accumulation of extracellular matrix proteins secreted by hepatic myofibroblasts plays an important role in disease progression. Activated hepatic stellate cells (HSCs) have been identified as the primary source of myofibroblasts in animal models of hepatotoxic liver injury; however, so far HSC activation and plasticity have not been thoroughly investigated in the context of NASH-related fibrogenesis. Here we have determined the time-resolved changes in the HSC transcriptome during development of Western diet- and fructose-induced NASH in mice, a NASH model recapitulating human disease. Intriguingly, HSC transcriptional dynamics are highly similar across disease models pointing to HSC activation as a point of convergence in the development of fibrotic liver disease. Bioinformatic interrogation of the promoter sequences of activated genes combined with loss-of-function experiments indicates that the transcriptional regulators ETS1 and RUNX1 act as drivers of NASH-associated HSC plasticity. Taken together, our results implicate HSC activation and transcriptional plasticity as key aspects of NASH pathophysiology.

Using fixed financial triggers for incentive plans.

Of course, some organizations are making no changes at all, because they don't believe that financial performance will justify paying even small awards. Healthcare organizations with executive incentive compensation plans need to review existing plans with their compensation committees. Merely leaving in place incentive plans developed prior to BBA may be doing a dis-service to the executive teams, the hospital, and the board. Using the incentive plan to focus management's attention on a few key areas is still relevant, maybe more so than ever. A complete review of incentive plans--participation, opportunity levels, financial triggers, performance measures, and other factors--is an important element of total executive compensation, probably now more than ever.

Annual survey: executive compensation under fire.

Compensation of health care executives has continued to grow, largely pushed along by such factors as continuing turnover in top management positions in hospitals, according to the 1992 Hay hospital management/professional survey of compensation and benefits data from over 1,200 U.S. hospitals. And although pay increases are moving up faster among top hospital executives than in industry, overall hospital executive pay still lags. In addition, survey results look at such issues as linking executive pay to various measures of performance.

Assessment of change-agent expectations in reversal-to-baseline designs.

Questionnaires similar to those used in previous research to assess behavioral expectations produced by differing reversal-to-baseline rationales were presented to 160 male and female parents in rural South Dakota. Given two case histories, respondents were asked to predict, as simulated change agents, the frequency of problem behavior during reversal in an ABAB design intervention. The five rationales for reversal were: (a) withdrawal, (b) withdrawal and counter-expectancy, (c) problem switch and counter-expectancy, (d) fade and counter-expectancy and (e) inert treatment and counter-expectancy. While obtained means were close to those of a previous study, there were no significant sex or treatment effects. This fails to confirm the earlier results obtained from university undergraduates. Implications for internal validity of ABAB designs are discussed.

Urinary tract infections with antibiotic resistant organisms in catheterized nursing home patients.

Long-term use of indwelling urinary catheters in nursing home (NH) patients is a potential cause of significantly morbidity. We retrospectively studied 10 NH patients with chronic indwelling urinary catheters. Sixty-four percent of all 84 antibiotic courses prescribed were for bacteriuria alone without clinical infection. Seventy percent of 63 antibiotic courses were followed by bacteriuria with organisms resistant to the antibiotic administered. Bacteria isolated from NH patients often displayed greater resistance to specific antibiotics than those isolated from hospitalized patients. Four of the 20 urinary tract infections were associated with bacteremia. Three episodes of bacteremia were with highly-resistant organisms and one was fatal. Use of urinary catheters and inappropriate use of antibiotics in NH patients results in urinary tract colonization and infection with resistant bacteria and is an important cause of morbidity and mortality.

Psychiatric aspects of voluntary sterilization in young, childless women.

An increasing number of young, childless women currently seek tubal ligation for fertility control. They state that they have no maternal aspirations and that available contraceptive methods are not safe enough. This aspect of voluntary sterilization has received little attention by psychiatrists in the past. This paper presents a psychological picture of seven women with a particular focus on some psychodynamic considerations underlying their wish to remain childless and the role of the psychiatrist in the decision-making process for this procedure.

Mania and milieu: treatment of manics in a therapeutic community.

The authors observed the management of 35 manic patients admitted to a 32-bed general hospital unit that emphasized milieu treatment. They concluded that the principles of treatment derived from the therapeutic community model--democratization and permissiveness--are generally incompatible with the effective treatment of manic patients, who can be a strong disruptive force on the patient and staff community. The authors describe approaches to managing manic patients in four phases--preadmission evaluation, and the postadmission, middle, and termination phases of inpatient treatment. They stress that milieu modifications are necessary to meet individual treatment needs.

Demographic and clinical characteristics of black psychiatric patients in a private general hospital.

A study of 419 first admissions to a private general hospital psychiatric inpatient unit showed that only 8.8 per cent were blacks, while 23 per cent of the population in the community were blacks. When compared to white patients, blacks were much less likely to be rerred for hospitalization by private sources, were substantially younger, and had shorter hospitalizations. The most common diagnosis for blacks was paranoid schizophrenia. The authors conclude that despite the widespread availability of third-party insurance coverage, blacks use the private general hospital less ofter than whites and their patterns of use are substantially different.