MicroRNA-150 modulates intracellular Ca2+ levels in naïve CD8+ T cells by targeting TMEM20

Regulation of intracellular Ca2+ signaling is a major determinant of CD8+ T cell responsiveness, but the mechanisms underlying this regulation of Ca2+ levels, especially in naïve CD8+ T cells, are not fully defined. Here, we showed that microRNA-150 (miR-150) controls intracellular Ca2+ levels in naïve CD8+ T cells required for activation by suppressing TMEM20, a negative regulator of Ca2+ extrusion. miR-150 deficiency increased TMEM20 expression, which resulted in increased intracellular Ca2+ levels in naïve CD8+ T cells. The subsequent increase in Ca2+ levels induced expression of anergy-inducing genes, such as Cbl-b, Egr2, and p27, through activation of NFAT1, as well as reduced cell proliferation, cytokine production, and the antitumor activity of CD8+ T cells upon antigenic stimulation. The anergy-promoting molecular milieu and function induced by miR-150 deficiency were rescued by reinstatement of miR-150. Additionally, knockdown of TMEM20 in miR-150-deficient naïve CD8+ T cells reduced intracellular Ca2+ levels. Our findings revealed that miR-150 play essential roles in controlling intracellular Ca2+ level and activation in naïve CD8+ T cells, which suggest a mechanism to overcome anergy induction by the regulation of intracellular Ca2+ levels115Ysciescopu

Evaluating a shared decision-making intervention regarding dialysis modality: development and validation of self-assessment items for patients with chronic kidney disease

Background Shared decision-making is a two-way symmetrical communication process in which clinicians and patients work together to achieve the best outcome. This study aimed to develop self-assessment items as a decision aid for choosing a dialysis modality in patients with chronic kidney disease (CKD) and to assess the construct validity of the newly developed items. Methods Five focus group interviews were performed to extract specific self-assessment items regarding patient values in choosing a dialysis modality. After survey items were refined, a survey of 330 patients, consisting of 152 hemodialysis (HD) and 178 peritoneal dialysis (PD) patients, was performed to validate the self-assessment items. Results The self-assessment for the decision aid was refined to 35 items. The structure of the final items appeared to have three dimensions of factors; health, lifestyle, and dialysis environment. The health factor consisted of 12 subscales (α = 0.724), the lifestyle factor contained 11 subscales (α = 0.624), and the dialysis environment factor was represented by 12 subscales (α = 0.694). A structural equation model analysis showed that the relationship between the decision aid factors (health, lifestyle, and dialysis environment), patients’ CKD perception, and cognition of shared decision-making differed between HD patients and PD patients. Conclusion We developed and validated self-assessment items as part of a decision aid to help patients with CKD. This attempt may assist CKD patients in making informed and shared decisions closely aligned with their values when considering dialysis modality

Comparison between Matched Related and Alternative Donors of Allogeneic Hematopoietic Stem Cells Transplanted into Adult Patients with Acquired Aplastic Anemia: Multivariate and Propensity Score-Matched Analysis

We retrospectively compared the outcomes of 225 patients with adult acquired aplastic anemia (AA) who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT) from matched related donors (MRDs), and those treated by alloHSCT from alternative donors (ADs). Univariate and multivariate analyses of factors associated with survival were performed. Multivariate analysis showed that age at alloHSCT of ≤31 years, MRD, successful engraftment, absence of acute graft-versus-host disease (aGVHD), and platelet engraftment at ≤21 days, were independent predictors of longer survival. In addition, time to aGVHD and cumulative nonrelapse mortality (NRM) were better in MRD than in AD recipients. Using propensity score matching (PSM), we performed a case-control study comparing 25 patients in each group who underwent alloHSCT from MRDs and ADs. Pretransplantation clinical factors were well balanced in either group. Median survival time was similar, and no statistically significant difference in transplantation outcomes was apparent when MRD and AD recipients were compared. In conclusion, our results suggest that alloHSCT from an AD should be considered earlier in adult patients with AA who do not have an MRD

Clinical efficacy of body mass index as predictor of in vitro fertilization and embryo transfer outcomes

The aim of this study was to evaluate the clinical efficacy of body mass index (BMI) as a predictor of in vitro fertilization and embryo transfer (IVF-ET) outcomes. Two hundred twenty-three IVF-ET cycles in 164 patients under 37 yr using GnRH agonist long protocols were included in this retrospective study. All of the selected cases were divided into two groups by a cutoff of 24 kg/m2 and these two groups were compared in regard to the outcomes of IVF-ET. There were no significant differences between group 1 (BMI or = 24 kg/m2) in age, basal serum FSH level, estradiol (E2) level and endometrial thickness on hCG day, number of retrieved oocytes and transferred embryos. However, higher doses of gonadotropins were used in group 2 (30.8+/-12.7 ampoules vs. 35.4+/-15.3 ampoules, p=0.051). The clinical pregnancy rate was significantly lower in group 2 (25.9% vs. 10.5%, p=0.041) and implantation rate tended to be lower in group 2 (12.7% vs. 6.8%, p=0.085). BMI > or = 24 kg/m2 can be a candidate prognosticator of IVF-ET outcomes

Noninvasive predictors of nonalcoholic steatohepatitis in Korean patients with histologically proven nonalcoholic fatty liver disease

Background/AimsThe aims of this study were (1) to identify the useful clinical parameters of noninvasive approach for distinguishing nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver disease (NAFLD), and (2) to determine whether the levels of the identified parameters are correlated with the severity of liver injury in patients with NASH.MethodsOne hundred and eight consecutive patients with biopsy-proven NAFLD (age, 39.8±13.5 years, mean±SD; males, 67.6%) were prospectively enrolled from 10 participating centers across Korea.ResultsAccording to the original criteria for NAFLD subtypes, 67 patients (62.0%) had NASH (defined as steatosis with hepatocellular ballooning and/or Mallory-Denk bodies or fibrosis ≥2). Among those with NAFLD subtype 3 or 4, none had an NAFLD histologic activity score (NAS) below 3 points, 40.3% had a score of 3 or 4 points, and 59.7% had a score >4 points. Fragmented cytokeratin-18 (CK-18) levels were positively correlated with NAS (r=0.401), as well as NAS components such as lobular inflammation (r=0.387) and ballooning (r=0.231). Fragmented CK-18 was also correlated with aspartate aminotransferase (r=0.609), alanine aminotransferase (r=0.588), serum ferritin (r=0.432), and the fibrosis stage (r=0.314). A fragmented CK-18 cutoff level of 235.5 U/L yielded sensitivity, specificity, and positive and negative predictive values of 69.0%, 64.9%, 75.5% (95% CI 62.4-85.1), and 57.1% (95% CI 42.2-70.9), respectively, for the diagnosis of NASH.ConclusionsSerum fragmented CK-18 levels can be used to distinguish between NASH and NAFL. Further evaluation is required to determine whether the combined measurement of serum CK-18 and ferritin levels improves the diagnostic performance of this distinction

Primary Cardiac Angiosarcoma Presenting With Cardiac Tamponade

Primary cardiac angiosarcoma is a very rare disease with a poor prognosis. We report a case of a patient with a primary cardiac angiosarcoma who presented with cardiac tamponade; the angiosarcoma was successfully resected surgically

Clinical Efficacy of Body Mass Index as Predictor of In Vitro Fertilization and Embryo Transfer Outcomes

The aim of this study was to evaluate the clinical efficacy of body mass index (BMI) as a predictor of in vitro fertilization and embryo transfer (IVF-ET) outcomes. Two hundred twenty-three IVF-ET cycles in 164 patients under 37 yr using GnRH agonist long protocols were included in this retrospective study. All of the selected cases were divided into two groups by a cutoff of 24 kg/m2 and these two groups were compared in regard to the outcomes of IVF-ET. There were no significant differences between group 1 (BMI <24 kg/m2) and group 2 (BMI ≥ 24 kg/m2) in age, basal serum FSH level, estradiol (E2) level and endometrial thickness on hCG day, number of retrieved oocytes and transferred embryos. However, higher doses of gonadotropins were used in group 2 (30.8±12.7 ampoules vs. 35.4±15.3 ampoules, p=0.051). The clinical pregnancy rate was significantly lower in group 2 (25.9% vs. 10.5%, p=0.041) and implantation rate tended to be lower in group 2 (12.7% vs. 6.8%, p=0.085). BMI ≥ 24 kg/m2 can be a candidate prognosticator of IVF-ET outcomes