Suppressive effects of vitamin C-treated induced-regulatory T cells on heart allograft rejection under vitamin C-deficient or -sufficient conditions.

Foxp3 stability of vitamin C-treated induced-regulatory T cells (V-iTregs) is superior to that of conventional iTregs (C-iTregs). However, the role of V-iTregs in allograft rejection under vitamin C-deficient conditions, such as those seen in humans, remains unclear. We aimed to elucidate the role of vitamin C treatment on generation and maintenance of iTregs from gulo knockout (Gulo-KO) mice as well as wild type (WT) mice, and in vitro and in vivo suppressive effects of V-iTregs on heart allograft rejection in either Gulo-KO or WT recipient mice. Conversion efficiency of iTregs was similar between C- and V-iTregs in both WT and Gulo-KO mice. V-iTregs from WT or Gulo-KO mice showed better in vitro Foxp3 stability than C-iTregs, although there was no difference between WT V-iTregs and Gulo-KO V-iTregs. Furthermore, V-iTregs from WT or Gulo-KO mice suppressed in vitro T cell proliferation better than C-iTregs. Heterotrophic heart transplantation from BALB/c mice to WT or vitamin C-deficient Gulo-KO C57BL/6J mice was performed following adoptive transfer of C- or V-iTregs. V-iTregs as well as C-iTregs prolonged heart allograft survival in WT and Gulo-KO mice. However, there was no difference between the C- and V-iTreg groups. Supplementation of low- or high-dose vitamin C did not induce significant changes in heart allograft survival in Gulo-KO recipients that had received V-iTregs. In conclusion, V-iTregs do not exert better suppressive effects on heart allograft survival than C-iTregs in either WT or vitamin C-deficient recipients.

[Job Analysis of Nurse Care Coordinators for Chronic Illness Management in Primary Care Settings: Using Developing a Curriculum Process].

PURPOSE: This study aimed to conduct a job analysis of nurse carecoordinators and to identify the frequency, importance and difficulty of each task of their job. METHODS: A committee for developing a curriculum (DACUM) was formed and members of the committee defined nurse care coordinators' jobs and enumerated the duties, tasks and task elements by applying the DACUM technique. Then nurse care coordinators enrolled in the pilot project evaluated the frequency, importance and difficulty of each task. RESULTS: From the job descriptions of nurse care coordinators, we identified 12 duties and 42 tasks. Each task comprised 1~5 task elements. Among tasks, 'assess the patient's general health status' was carried out most frequently. Nurse care coordinators perceived that 'check vital signs' and'strengthen patient competence to promote health behaviors' were more important than all other tasks. The most difficult task was 'develop professionalism as a nurse care coordinator'. CONCLUSION: The nurse care coordinators' roles developed in this study will serve as the key guidelines for human resource management of care coordinators. Further, job specifications for nurse care coordinators need to be developed, which is necessary for designing education and training programs. We also need to integrate primary health care as an essential component in nursing education.

Granulocyte Colony-Stimulating Factor Attenuates Renal Ischemia-Reperfusion Injury by Inducing Myeloid-Derived Suppressor Cells.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) can increase populations of myeloid-derived suppressor cells, innate immune suppressors that play an immunoregulatory role in antitumor immunity. However, the roles of myeloid-derived suppressor cells and G-CSF in renal ischemia-reperfusion injury remain unclear. METHODS: We used mouse models of ischemia-reperfusion injury to investigate whether G-CSF can attenuate renal injury by increasing infiltration of myeloid-derived suppressor cells into kidney tissue. RESULTS: G-CSF treatment before ischemia-reperfusion injury subsequently attenuated acute renal dysfunction, tissue injury, and tubular apoptosis. Additionally, G-CSF treatment suppressed renal infiltration of macrophages and T cells as well as renal levels of IL-6, MCP-1, IL-12, TNF-α, and IFN-γ, but it increased levels of IL-10, arginase-1, and reactive oxygen species. Moreover, administering G-CSF after ischemia-reperfusion injury improved the recovery of renal function and attenuated renal fibrosis on day 28. G-CSF treatment increased renal infiltration of myeloid-derived suppressor cells (F4/80-CD11b+Gr-1int), especially the granulocytic myeloid-derived suppressor cell population (CD11b+Ly6GintLy6Clow); splenic F4/80-CD11b+Gr-1+ cells sorted from G-CSF-treated mice displayed higher levels of arginase-1, IL-10, and reactive oxygen species relative to those from control mice. Furthermore, these splenic cells effectively suppressed in vitro T cell activation mainly through arginase-1 and reactive oxygen species, and their adoptive transfer attenuated renal injury. Combined treatment with anti-Gr-1 and G-CSF showed better renoprotective effects than G-CSF alone, whereas preferential depletion of myeloid-derived suppressor cells by pep-G3 or gemcitabine abrogated the beneficial effects of G-CSF against renal injury. CONCLUSIONS: G-CSF induced renal myeloid-derived suppressor cells, thereby attenuating acute renal injury and chronic renal fibrosis after ischemia-reperfusion injury. These results suggest therapeutic potential of myeloid-derived suppressor cells and G-CSF in renal ischemia-reperfusion injury.

Anti-CD45RB Antibody Therapy Attenuates Renal Ischemia-Reperfusion Injury by Inducing Regulatory B Cells.

BACKGROUND: Regulatory B cells are a newly discovered B cell subset that suppresses immune responses. Recent studies found that both anti-CD45RB and anti-Tim-1 treatments regulate immune responses by inducing regulatory B cells; however, the role of these cells in renal ischemia-reperfusion injury (IRI) is unknown. METHODS: Using mouse models, including T cell-deficient (RAG1 knockout and TCRα knockout) mice and B cell-deficient (µMT) mice, we investigated the effects of regulatory B cells and anti-CD45RB on IRI and the mechanisms underlying these effects. RESULTS: Adoptive transfer of regulatory B cells before or after IRI attenuated renal IRI. Anti-CD45RB treatment with or without anti-Tim-1 before IRI increased renal infiltration of CD19+Tim-1+ regulatory B and regulatory T cells. Anti-CD45RB decreased serum creatinine levels, pathologic injury score, tubular apoptosis, and proinflammatory cytokines levels, whereas IL-10 levels increased. Following IRI, anti-CD45RB with or without anti-Tim-1 also induced regulatory B cells, improving renal function and tubular regeneration. In RAG1 knockout mice with B cell transfer, TCRα knockout mice, and wild-type mice with T cell depletion, anti-CD45RB increased regulatory B cells and attenuated IRI. However, anti-CD45RB did not attenuate IRI in RAG1 knockout mice with T cell transfer or µMT mice and induced only mild improvement in wild-type mice with B cell depletion. Furthermore, B cell-deficient mice receiving B cells from IL-10 knockout mice (but not from wild-type mice) did not show renal protection against IRI when treated with anti-CD45RB. CONCLUSIONS: Anti-CD45RB treatment attenuated acute renal injury and facilitated renal recovery after IRI through induction of IL-10+ regulatory B cells, pointing to anti-CD45RB as a potential therapeutic strategy in renal IRI.

Standardization Study of the Korean Version of the Stages of Change Readiness and Treatment Eagerness Scale for Smoking Cessation (K-SOCRATES-S) and Its Predictive Validity.

OBJECTIVE: The purpose of the study was to develop the Korean version of the Stage of Change Readiness and Treatment Eagerness Scale for Smoking Cessation (K-SOCRATES-S) based on the Korean version of the Stages of Readiness for Change and Eagerness for Treatment scale (K-SOCRATES). This paper also demonstrates its reliability and validity among patients with nicotine dependence in South Korea. METHODS: At seven healthcare promotion centers in Gyeonggi-do, 333 male smokers aged 20 to 70 who visited smoking cessation clinic were recruited for this study and the K-SOCRATES-S was administered. After three months, the number of respondents who successfully stopped smoking was assessed by testing their urine cotinine level. Subsequently, exploratory factor analysis was performed to verify the reliability and validity of the K-SOCRATES-S. Also, a logistic regression analysis was performed to examine the variables that can predict the successful cessation of smoking on subscales of the K-SOCRATES-S. RESULTS: Exploratory factor analysis of the K-SOCRATES-S showed that the scale consisted of three factors: Taking Steps, Recognition, and Ambivalence. The scales measuring Taking Steps and Recognition in this scale had a significantly positive correlation with the scores observed on Kim's smoking cessation motivation scale. The scales measuring Taking Steps and Recognition had a significantly negative correlation with Ambivalence. Overall, the results indicate that the K-SOCRATES-K scale showed high validity. CONCLUSION: The K-SOCRATES-S developed in the present study is highly reliable and valid for predicting a patient's likelihood of success in quitting smoking among patients who want to cease smoking.