The backfiring effects of monetary and gift incentives on Covid-19 vaccination intentions.

We provide evidence that material inducements for Covid-19 vaccination may backfire. Results from a hypothetical survey experiment in China (N = 1365) show incentives of 8-125 USD reduce vaccine uptake intentions compared to simply offering vaccination for free. Ours is the first Covid-19 vaccine study to separately consider and directly compare the effects of monetary and goods-based incentives, both of which have been widely employed by countries seeking to increase uptake; we demonstrate that both types backfire equally. Results are compared against the burgeoning literature on Covid-19 vaccine incentives.

Crucial positively charged residues for ligand activation of the GPR35 receptor.

GPR35 is a G protein-coupled receptor expressed in the immune, gastrointestinal, and nervous systems in gastric carcinomas and is implicated in heart failure and pain perception. We investigated residues in GPR35 responsible for ligand activation and the receptor structure in the active state. GPR35 contains numerous positively charged amino acids that face into the binding pocket that cluster in two distinct receptor regions, TMH3-4-5-6 and TMH1-2-7. Computer modeling implicated TMH3-4-5-6 for activation by the GPR35 agonists zaprinast and pamoic acid. Mutation results for the TMH1-2-7 region of GPR35 showed no change in ligand efficacies at the K1.32A, R2.65A, R7.33A, and K7.40A mutants. However, mutation of arginine residues in the TMH3-4-5-6 region (R4.60, R6.58, R3.36, R(164), and R(167) in the EC2 loop) had effects on signaling for one or both agonists tested. R4.60A resulted in a total ablation of agonist-induced activation in both the ß-arrestin trafficking and ERK1/2 activation assays. R6.58A increased the potency of zaprinast 30-fold in the pERK assay. The R(167)A mutant decreased the potency of pamoic acid in the ß-arrestin trafficking assay. The R(164)A and R(164)L mutants decreased potencies of both agonists. Similar trends for R6.58A and R(167)A were observed in calcium responses. Computer modeling showed that the R6.58A mutant has additional interactions with zaprinast. R3.36A did not express on the cell surface but was trapped in the cytoplasm. The lack of surface expression of R3.36A was rescued by a GPR35 antagonist, CID2745687. These results clearly show that R4.60, R(164), R(167), and R6.58 play crucial roles in the agonist initiated activation of GPR35.

Prospects of embryonic stem cells in treatment of hematopoietic disorders.

Cellular therapies derived from embryonic stem (ES) cells have gained a renewed interest with the experimental demonstration that an embryonic stem cell lines can be established from human blastocyst-stage embryos and prompted to differentiate into almost all types of cells present in the body including hematopoietic cells. Hematopoiesis is a series of cellular processes whereby short-lived mature blood cells are continuously replenished from a pool of rare pluripotential hematopoietic stem cells, in a highly orchestrated process. Aberrances in this intricate process may lead to a malignancy of essential blood-forming organs, causing diseases such as leukemia, aplastic anemia, lymphoma, myelodysplasia and myeloproliferative disorders. Embryonic stem cells show great potential and it may be technologically feasible to transplant differentiated ES cells and to cure various kinds of blood disorders. Understanding the biology of ES cell derived hematopoiesis may lead to the development of co-transplantation protocols that will result in a decreased morbidity and mortality by providing safer and simpler transplantation procedures for patients with malignant and non-malignant conditions. The potential utility of ES cells for gene therapy, tissue engineering and the treatment of a wide variety of currently untreatable diseases is simply too essential to ignore, however, our knowledge and ability to deliver these forms of therapy in a safe and efficient manner requires additional advances in the understanding of the basic biology of ES cells. In this article, we will discuss the factors and methodologies responsible for the differentiation of ES cells into hematopoietic progenitors and their potential to treat different blood related diseases.

Consumers and families as partners in implementing evidence-based practice.

Evidence-based practices represent an extremely important advance in the mental health system, and NAMI continues its support of efforts to develop and implement these interventions. Moving forward, the authors envision consumers and family members playing a much greater role in developing and promulgating EBP. Individually and corporately, consumers can: facilitate research that will expedite equitable implementation of existing and new EBPs; play a significant role in providing services; play a lead role in promoting policies that support EBP implementation through the development and use of advocacy toolkits; influence provider adaptation of EBP through the broad development and testing of resources that urge EBP consumerism; and, advance through the monitoring of EBP. These consumer-led activities generally have been relegated to a lower level of importance in the current research, policy, and funding environment leading to poorly developed partnerships and "buy in" from the consumer community. It is important that the level of importance of these activities and the role of consumers and families be rethought. Further advancement of EBP will require implementing a three-track program of research, including a much greater focus on action research and the involvement of consumers as research and evaluation partners. This is the fastest and most effective way to achieve breakthrough results in practices for treating people with serious mental illnesses and to address the serious and growing problem of racial and cultural disparities and the disconnect that causes between those individuals and the means to their recovery. The hope of consumers and families rest on the ability to initiate action now.