Social exclusion in primary healthcare settings: the time for measurement has come

Social exclusion is a concept that has been discussed and debated in many disciplines in recent decades. In 2006 the WHO Social Exclusion Knowledge Network published a report detailing their work explaining the relevance of social exclusion to the domain of health. As part of that work, the authors formulated a complex definition of social exclusion that has proven difficult to adapt or operationalize in healthcare settings. We looked at this WHO work, and at other published evidence, and decided that social exclusion is a concept that is worth measuring at the individual level in healthcare settings. We suggest that the primary healthcare space, in particular, is an ideal setting in which to do that measurement. We have examined existing social exclusion measurement tools, and scrutinised the approaches taken by their authors, and the various domains they measured. We now propose to develop and validate such a tool for use in primary healthcare settings

Additional file 1: of Measuring social exclusion in healthcare settings: a scoping review

Contains the background literature for each measurement tool in Tables 1 and 2. (DOCX 26 kb

The top 20 upregulated and downregulated genes in tonsil follicular B cells as compared to cord blood transitional B cells.

The top 20 upregulated and downregulated genes in tonsil follicular B cells as compared to cord blood transitional B cells.</p

Surface IgM and IgD expression increases independently of CD23 expression in transitional B cell maturation.

Transitional B cells were cultured with IL-4 or R848+IL-4 and examined for R123 extrusion (A), CD21 and CD23 expression (B), and sIgM and sIgD expression (C). Although CD23 expression and R123 extrusion in cultures stimulated with IL-4 alone is less than in cultures stimulated with R848+IL-4, most R123neg cells in both cultures express high levels of sIgM and sIgD. (EPS)</p

Sorting strategies for human cord blood transitional B cells and human tonsil follicular B cells.

(A) Cord blood mononuclear cells were stained with R123 and chased for 3 hours. Following R123 pulse/chase, cells were stained with fluorochrome-conjugated antibodies against CD3, CD19, CD24, and CD38. Transitional B cells were sorted based on high R123 expression following the initial gating strategy. (B) Tonsil mononuclear cells were isolated from fresh tonsil tissue via mechanical homogenization and Ficoll density gradient centrifugation. Cell suspensions were stained with fluorochrome-conjugated antibodies against CD3, CD19, CD23, IgD, IgM. Follicular B cells were sorted as CD3-, CD19+, CD23+, IgD+, IgM+/-.</p

Transitional B cells from human cord blood and peripheral blood mononuclear cells.

Transitional B cells were FACS-sorted based on expression of surface markers, CD19, CD24, CD38 and staining by Rhodamine 123. (A) Total cells were gated based on lymphocyte morphology, followed by gates on viable CD19+CD3- cells, and finally Rhodamine 123 fluorescence. (B and C) Expression of sIgD, CD21, CD23, CD5, and sIgM are shown as histogram plots of median fluorescence intensity (MFI) for high (B) and low (C) Rhodamine 123 staining B cells. (D) Freshly isolated PBMCs were labeled with fluorochrome-conjugated antibodies against CD19, CD24, CD38, CD21, CD23, IgD, and IgM. Total cells were gated based on lymphocyte morphology, followed by viable CD19+ cells, and CD38hi CD24hi expression. Expression of CD23, sIgM, CD21, and sIgD by these CD38hi CD24hi transitional B cells are shown as MFI histogram plots (shaded histograms are isotype controls).</p

Induction of transitional B cell development into memory B cells.

FACS-sorted transitional B cells were cultured with IL4, R848+IL4, CpG, or CpG+IL4 for 2 days and evaluated for expression of CD23 and the B cell memory marker, CD27. (A) Follicular B cell maturation was determined by R123 extrusion and CD23 acquisition in cultures stimulated with IL-4 (panel 1), R848+IL-4 (panel 2), CpG (panel 3), and CpG+IL-4 (panel 4). Boxed area corresponds to R123negCD23+ mature B cells. (B) CD27 and CD23 expression of cultures stimulated with IL-4 (panel 1), R848+IL-4 (panel 2), CpG (panel 3), and CpG+IL-4 (panel 4). (C) Pie-chart display of relative amounts of cells expressing the following surface phenotypes: CD23+CD27-, purple; CD23+CD27+, blue; CD23-CD27+, green; CD23-CD27-, orange. Culture stimulation conditions are shown above each pie chart. (D-G) sIgM and sIgD expression of subpopulations of cells expressing different combinations of CD23 and CD27 in cultures stimulated with IL-4 (panel 1), R848+IL-4 (panel 2), CpG (panel 3), and CpG+IL-4 (panel 4).</p

Gene expression analysis of transitional B cells stimulated with CpG+IL-4 or CpG alone.

Purified cord blood transitional B cells were cultured with various stimuli, cultured cells were isolated on day 2 and cDNA was prepared for real-time qPCR. (A) CD23 and CD27 expression of cells cultured with IL-4 (panel 1), R848+IL-4 (panel 2), CpG (panel 3), and CpG+IL-4 (panel 4). (B) Gene expression fold change was calculated using CpG-stimulated cultures as the reference condition as compared to cultures stimulated with IL4 (blue), R848+IL-4 (red), and CpG+IL-4 (green). Transcripts evaluated were CD27, PRDM1, FCER2(CD23), PTPN6, ADAM28, and TNFRSF17. (C) List of upregulated genes for tonsil follicular B cells as compared to cord blood transitional B cells from transcriptome analysis.</p

Transcriptome analysis of tonsil follicular B cells and cord blood transitional B cells.

(A) Mean differences plot showing the gene expression fold change for follicular and transitional B cells. Statistically significant differences in gene expression between tonsil follicular B cells and cord blood transitional B cells are in red. (B) RT-qPCR confirmation of select genes (FCER2, RUNX1, and ADAM28) identified from the AmpliSeq analysis in purified FO and Tr B cells. Gene expression fold change is expressed as the ratio of gene expression in follicular B cells/transitional B cells.</p

Pathway analysis of tonsil follicular B cells and cord blood transitional B cells.

Heatmap display of follicular B cells (black band) and transitional B cells (yellow band) from three individual samples for each cell type. Pathways analyzed were (A) IL-6 signaling, NF-kB signaling, PKA signaling; (B) BCR signaling, Cyclins & Cell Cycle Regulation, Th1/Th2 activation; (C) IL-4 signaling, Notch signaling, PI3K signaling in B lymphocytes. Specific genes of interest are boxed in red. Heat map keys are provided on the right of each figure.</p