Liver‐Regenerative Transplantation: Regrow and Reset

Liver transplantation, either a partial liver from a living or deceased donor or a whole liver from a deceased donor, is the only curative therapy for severe end‐stage liver disease. Only one‐third of those on the liver transplant waiting list will be transplanted, and the demand for livers is projected to increase 23% in the next 20 years. Consequently, organ availability is an absolute constraint on the number of liver transplants that can be performed. Regenerative therapies aim to enhance liver tissue repair and regeneration by any means available (cell repopulation, tissue engineering, biomaterials, proteins, small molecules, and genes). Recent experimental work suggests that liver repopulation and engineered liver tissue are best suited to the task if an unlimited availability of functional induced pluripotent stem (iPS)–derived liver cells can be achieved. The derivation of iPS cells by reprogramming cell fate has opened up new lines of investigation, for instance, the generation of iPS‐derived xenogeneic organs or the possibility of simply inducing the liver to reprogram its own hepatocyte function after injury. We reviewed current knowledge about liver repopulation, generation of engineered livers and reprogramming of liver function. We also discussed the numerous barriers that have to be overcome for clinical implementation.     

The multitargeted receptor tyrosine kinase inhibitor linifanib (ABT-869) induces apoptosis through an Akt and glycogen synthase kinase 3β-dependent pathway

The FMS-like receptor tyrosine kinase 3 (FLT3) plays an important role in controlling differentiation and proliferation of hematopoietic cells. Activating mutations in FLT3 occur in patients with acute myeloid leukemia (AML; 15%-35%), resulting in abnormal cell proliferation. Furthermore, both adult and pediatric patients with AML harboring the FLT3 internal tandem duplication (ITD) mutation have a poor prognosis. Several inhibitors have been developed to target mutant FLT3 for the treatment of AML, yet the molecular pathways affected by drug inhibition of the mutated FLT3 receptor alone have not been characterized as yet. Linifanib (ABT-869) is a multitargeted tyrosine kinase receptor inhibitor that suppresses FLT3 signaling. In this article, we show that treatment with linifanib inhibits proliferation and induces apoptosis in ITD mutant cells in vitro and in vivo. We show that treatment with linifanib reduces phosphorylation of Akt and glycogen synthase kinase 3β (GSK3β). In addition, we show that inhibition of GSK3β decreases linifanib-induced apoptosis. This study shows the importance of GSK3 as a potential target for AML therapy, particularly in patients with FLT3 ITD mutations.     

Therapist and client race/ethnicity match: An examination of treatment outcome and process with rural older adults in the deep south

Abstract This study investigated the effects of race/ethnicity (r/e) match in cognitive-behavioral therapy with rural older adults. Races/ethnicities represented in this study were African-American and White. Treatment followed a CBT treatment protocol and was provided by MSWs to clients in their homes. Results indicated little evidence of differences in outcome and process for matched and non-matched dyads for number of sessions attended, changes in quality of life and psychological symptoms, overall quality of therapy sessions, or the number of sessions considered of unsatisfactory quality. Our findings are consistent with recent research on r/e matching and extend these findings to a sample of rural older adults.     

Therapist and client race/ethnicity match: An examination of treatment outcome and process with rural older adults in the deep south

Abstract

This study investigated the effects of race/ethnicity (r/e) match in cognitive-behavioral therapy with rural older adults. Races/ethnicities represented in this study were African-American and White. Treatment followed a CBT treatment protocol and was provided by MSWs to clients in their homes. Results indicated little evidence of differences in outcome and process for matched and non-matched dyads for number of sessions attended, changes in quality of life and psychological symptoms, overall quality of therapy sessions, or the number of sessions considered of unsatisfactory quality. Our findings are consistent with recent research on r/e matching and extend these findings to a sample of rural older adults.     

Associations Between Fear of Negative Evaluation and Eating Pathology During Intervention and 12-Month Follow-up

Fear of negative evaluation (FNE), a core feature of social anxiety disorder, has been prospectively related to eating pathology over and above other established risk factors, suggesting that it may be an important cognitive risk factor for eating disorders. The present study examined reciprocal longitudinal relations among FNE and eating disorder risk factors using a female undergraduate sample (N = 82) enrolled in an eating disorder prevention program. Cross-lagged panel analysis revealed that FNE was a determinant of subsequent body dissatisfaction and eating disorder symptoms. Fear of negative evaluation also predicted subsequent thin-ideal internalization among participants with high body mass index (BMI), but not among those with low BMI. Fear of negative evaluation did not predict future dietary restraint or negative affect but was itself predicted by prior levels of thin ideal internalization, body dissatisfaction, dietary restraint, and negative affect. Findings suggest that FNE may be a useful target for reducing body image concerns and maladaptive eating behavior.