Clinicians' experience of providing care: a rapid review.

BACKGROUND: Health care services internationally are refocussing care delivery towards patient centred, integrated care that utilises effective, efficient and innovative models of care to optimise patient outcomes and system sustainability. Whilst significant efforts have been made to examine and enhance patient experience, to date little has progressed in relation to provider experience. This review aims to explore this knowledge gap by capturing evidence of clinician experience, and how this experience is defined and measured in the context of health system change and innovation. METHODS: A rapid review of published and grey literature review was conducted utilising a rapid evidence assessment methodology. Seventy-nine studies retrieved from the literature were included in the review. Fourteen articles were identified from the grey literature search and one article obtained via hand searching. In total, 94 articles were included in the review. This study was commissioned by and co-designed with the New South Wales, Ministry of Health. RESULTS: Clinician experience of delivering health care is inconsistently defined in the literature, with identified articles lacking clarity regarding distinctions between experience, engagement and work-related outcomes such as job satisfaction. Clinician experience was commonly explored using qualitative research that focused on experiences of discrete health care activities or events in which a change was occurring. Such research enabled exploration of complex experiences. In these contexts, clinician experience was captured in terms of self-reported information that clinicians provided about the health care activity or event, their perceptions of its value, the lived impacts they experienced, and the specific behaviours they displayed in relation to the activity or event. Moreover, clinician's experience has been identified to have a paucity of measurement tools. CONCLUSION: Literature to date has not examined clinician experience in a holistic sense. In order to achieve the goals identified in relation to value-based care, further work is needed to conceptualise clinician experience and understand the nature of measurement tools required to assess this. In health system application, a broader 'clinician pulse' style assessment may be valuable to understand the experience of clinical work on a continuum rather than in the context of episodes of change/care.

C-terminal binding protein: A metabolic sensor implicated in regulating adipogenesis.

The development of mature adipocytes from preadipocyte precursor cells requires coordinated changes in gene expression. Management of these expression changes relies on the actions of both DNA-binding transcription factors and their coregulators. Recent studies have identified the corepressor C-terminal binding protein (CtBP) as a key transcriptional coregulator in adipose tissue. CtBP proteins work with several different partner proteins to regulate the development of both white and brown adipocytes. CtBP is of particular interest as it binds to NAD(+)/NADH and may respond to the metabolic state of the cell, thereby linking changes in nutrient levels to transcriptional outcomes.

GATA proteins work together with friend of GATA (FOG) and C-terminal binding protein (CTBP) co-regulators to control adipogenesis.

GATA transcription factors have been implicated in controlling adipogenesis in Drosophila and in mammals. In mammals, both GATA2 and GATA3 have been shown to be present in preadipocytes, and their silencing allows the onset of adipogenesis. Overexpression of GATA proteins blocks adipogenesis in cellular assays. GATA factors have been found to operate through recruiting cofactors of the Friend of GATA (FOG) family. FOG proteins, in turn, recruit co-regulators, including C-terminal binding proteins (CTBPs). We have investigated whether FOGs and CTBPs influence adipogenesis. We found that both FOG1 and FOG2 are expressed in cells prior to adipogenesis but are down-regulated as adipogenesis proceeds. Overexpression of FOG1 or FOG2 interferes with adipogenesis. Mutant versions of FOG2 unable to bind CTBP or GATA proteins are impaired in their inability to inhibit adipogenesis. Finally, a mutant version of GATA2, unable to associate with FOGs, also displays abnormal activity and causes enhanced cell proliferation. These results implicate FOGs and CTBPs as partners of GATA proteins in the control of adipocyte proliferation and differentiation.

Introducing undergraduate students to real-time PCR.

An experiment is conducted, which in four 3 h laboratory sessions, introduces third year undergraduate Biochemistry students to the technique of real-time PCR in a biological context. The model used is a murine erythroleukemia cell line (MEL cells). These continuously cycling, immature red blood cells, arrested at an early stage in erythropoiesis, can be induced to progress further through the process by 72 h exposure to 1.8% DMSO. This gives a control cell sample and a DMSO-treated preparation. Students isolate RNA from both cell cultures, check its purity, yield and integrity by UV spectrophotometry and denaturing gel electrophoresis, then synthesized cDNA. The relative levels of three sequences: ß globin, amino levulinate synthase, and carbonic anhydrase-1 are estimated by real-time PCR, using 18S rRNA as the reference sequence. The changes in gene expression are robust and reproducible, enabling students to experience a "cutting edge" research technique in an undergraduate lab setting. While the undergraduate student experience in practical classes with such sensitive techniques is often mixed, the changes in gene expression in this model are sufficiently great that students can gain the satisfaction of consistent results. In addition they gain experience at setting up checks and controls at stages throughout a multistep process and an appreciation of the difference between a reaction which has gone to completion with one that is measured as a rate. This experiment would also complement cell biology projects involving red cell development. It could also be extended to more thoroughly investigate the technique of real-time PCR.

Targeted disruption of the basic Krüppel-like factor gene (Klf3) reveals a role in adipogenesis.

Krüppel-like factors (KLFs) recognize CACCC and GC-rich sequences in gene regulatory elements. Here, we describe the disruption of the murine basic Krüppel-like factor gene (Bklf or Klf3). Klf3 knockout mice have less white adipose tissue, and their fat pads contain smaller and fewer cells. Adipocyte differentiation is altered in murine embryonic fibroblasts from Klf3 knockouts. Klf3 expression was studied in the 3T3-L1 cellular system. Adipocyte differentiation is accompanied by a decline in Klf3 expression, and forced overexpression of Klf3 blocks 3T3-L1 differentiation. Klf3 represses transcription by recruiting C-terminal binding protein (CtBP) corepressors. CtBPs bind NADH and may function as metabolic sensors. A Klf3 mutant that does not bind CtBP cannot block adipogenesis. Other KLFs, Klf2, Klf5, and Klf15, also regulate adipogenesis, and functional CACCC elements occur in key adipogenic genes, including in the C/ebpalpha promoter. We find that C/ebpalpha is derepressed in Klf3 and Ctbp knockout fibroblasts and adipocytes from Klf3 knockout mice. Chromatin immunoprecipitations confirm that Klf3 binds the C/ebpalpha promoter in vivo. These results implicate Klf3 and CtBP in controlling adipogenesis.