Discordance between GLP-1R gene and protein expression in mouse pancreatic islet cells.

The insulinotropic actions of glucagon-like peptide 1 receptor (GLP-1R) in ß-cells have made it a useful target to manage type 2 diabetes. Metabolic stress reduces ß-cell sensitivity to GLP-1, yet the underlying mechanisms are unknown. We hypothesized that Glp1r expression is heterogeneous among ß-cells and that metabolic stress decreases the number of GLP-1R-positive ß-cells. Here, analyses of publicly available single-cell RNA-Seq sequencing (scRNASeq) data from mouse and human ß-cells indicated that significant populations of ß-cells do not express the Glp1r gene, supporting heterogeneous GLP-1R expression. To check these results, we used complementary approaches employing FACS coupled with quantitative RT-PCR, a validated GLP-1R antibody, and flow cytometry to quantify GLP-1R promoter activity, gene expression, and protein expression in mouse α-, ß-, and δ-cells. Experiments with Glp1r reporter mice and a validated GLP-1R antibody indicated that >90% of the ß-cells are GLP-1R positive, contradicting the findings with the scRNASeq data. α-cells did not express Glp1r mRNA and δ-cells expressed Glp1r mRNA but not protein. We also examined the expression patterns of GLP-1R in mouse models of metabolic stress. Multiparous female mice had significantly decreased ß-cell Glp1r expression, but no reduction in GLP-1R protein levels or GLP-1R-mediated insulin secretion. These findings suggest caution in interpreting the results of scRNASeq for low-abundance transcripts such as the incretin receptors and indicate that GLP-1R is widely expressed in ß-cells, absent in α-cells, and expressed at the mRNA, but not protein, level in δ-cells.

Shifting perspectives: a confirmatory factor analysis of the working alliance inventory (short form) with high-risk violent offenders.

The Working Alliance Inventory (WAI) is the most widely used measure of the therapeutic alliance. However, previous studies of the factor structure of the WAI have obtained disparate results. This study examined ratings from three rater perspectives (therapists, clients, and observers) in a rehabilitation program for high-risk violent prisoners with high PCL-psychopathy scores. The authors used confirmatory factor analysis with a short version of the WAI and examined one-, two-, and three-factor models. It was hypothesized that the context and client characteristics could alter the factor structure of the ratings. However, no differences were found in factor structure by perspective; the results from all rater perspectives suggested that a two-factor structure was the best fit for the data. Thus, we concluded that therapists, observers, and prisoners all saw the goals and task aspects of the therapeutic alliance as distinct from the bond component.

Do early therapeutic alliance, motivation, and stages of change predict therapy change for high-risk, psychopathic violent prisoners?

BACKGROUND: Examination of the extent of offenders' engagement in change, and in rehabilitation programmes, is important to understanding success or failure following rehabilitation. In treatment programmes, the alliance between therapist and offender, and the therapy process itself appear central to progress offenders make that may reduce their criminal risk. But research with offenders seldom has measured therapeutic alliance and clinical writing suggests that it is difficult to form an alliance with those not ready to change their behaviour; especially with higher risk and psychopathic offenders. AIMS AND METHODS: This study outlines the course of the therapeutic alliance in an 8-month treatment programme for high-risk, PCL-psychopathic violent prisoners. It examines relationships between early-treatment therapeutic alliance, therapists' global ratings of motivation to change, and initial stage of change on dynamic risk factors. In addition, it investigates which factors best predict who will complete treatment and change behaviourally during treatment. CONCLUSION: In this challenging, high-needs client group, early-programme stage of change, therapists' perceptions of motivation, therapeutic alliance and psychopathy did not predict how much change prisoners made. Regardless of initial levels, prisoners whose alliance increased the most over the course of treatment made the most change.