Loss of methylation at the IFNG promoter and CNS-1 is associated with the development of functional IFN-γ memory in human CD4(+) T lymphocytes.

Cytokine memory for IFN-γ production by effector/memory Th1 cells plays a key role in both protective and pathological immune responses. To understand the epigenetic mechanism determining the ontogeny of effector/memory Th1 cells characterized by stable effector functions, we identified a T-cell-specific methylation pattern at the IFNG promoter and CNS-1 in ex vivo effector/memory Th1 cells, and investigated methylation dynamics of these regions during the development of effector/memory Th1 cells. During Th1 differentiation, demethylation occurred at both the promoter and CNS-1 regions of IFNG as early as 16 h, and this process was independent of cell proliferation and DNA synthesis. Using an IFN-γ capture assay, we found early IFN-γ-producing cells from 2-day differentiating cultures acquired "permissive" levels of demethylation and developed into effector/memory Th1 cells undergoing progressive demethylation at the IFNG promoter and CNS-1 when induced by IL-12. Methylation levels of these regions in effector/memory Th1 cells of peripheral blood from rheumatoid arthritis patients correlated inversely with reduced frequencies of IFN-γ-producers, coincident with recruitment of effector/memory Th1 cells to the site of inflammation. Thus, after termination of TCR stimulation, IL-12 signaling potentiates the stable functional IFN-γ memory in effector/memory Th1 cells characterized by hypomethylation at the IFNG promoter and CNS-1.

Comparative study of virtual and traditional teaching methods on the interpretation of cardiac dysrhythmia in nursing students.

INTRODUCTION: Due to the importance of correct interpretation of electrocardiogram (ECG) in the quality of healthcare delivery, new educational methods are increasingly being implemented and evaluated. In this regard, the purpose of this study was to compare the traditional and virtual teaching methods on the interpretation of cardiac dysrhythmia in nursing students. METHODS: The present study is a quasi-experimental research with pretest and posttest design. Sixty nursing students in the seventh semester from schools of nursing in Urmia and Khoy cities were randomly assigned to two virtual and traditional education groups. Students' knowledge was measured by a researcher-made 30-item test. RESULTS: The mean and standard deviation of the students' scores in the traditional education group was 11.20 ± 4.41 and 14.40 ± 4.62 and in the virtual group was 11.30 ± 2.74 and 18.43 ± 4.68, pre- and post-training, respectively. Paired t-test showed a significant difference between the mean score of pretest and posttest in both types of training (P < 0.001). According to the results of independent sample t-test, there were no significant differences between the two groups before the training (P > 0.05). However, in the posttraining period, there were significant differences between traditional and virtual education groups (P < 0.001). CONCLUSION: Considering the results of this study, which shows the positive effects of virtual education method on nursing students' knowledge about cardiac dysrhythmia, this method can be used as an alternative or complementary method to the traditional education.

Neurocognitive dysfunction in systemic lupus erythematosus: association with antiphospholipid antibodies, disease activity and chronic damage.

INTRODUCTION: Systemic lupus erythematosus (SLE) is characterized by frequent neuropsychiatric involvement, which includes cognitive impairment (CI). We aimed at assessing CI in a cohort of Italian SLE patients by using a wide range of neurocognitive tests specifically designed to evaluate the fronto-subcortical dysfunction. Furthermore, we aimed at testing whether CI in SLE is associated with serum autoantibodies, disease activity and chronic damage. METHODS: Fifty-eight consecutive patients were enrolled. Study protocol included data collection, evaluation of serum levels of ANA, anti-dsDNA, anti-cardiolipin, anti-ß(2)-glycoprotein I, anti-P ribosomal, anti-endothelial cell, and anti-Nedd5 antibodies. SLEDAI-2000 and SLICC were used to assess disease activity and chronic damage. Patients were administered a test battery specifically designed to detect fronto-subcortical dysfunction across five domains: memory, attention, abstract reasoning, executive function and visuospatial function. For each patient, the raw scores from each test were compared with published norms, then transformed into Z scores (deviation from normal mean), and finally summed in the Global Cognitive Dysfunction score (GCDs). RESULTS: Nineteen percent of patients had mild GCDs impairment (GCDs 2-3), 7% moderate (GCDs 4-5) and 5% severe (GCDs≥6). The visuospatial domain was the most compromised (MDZs = -0.89±1.23). Anti-cardiolipin IgM levels were associated with visuospatial domain impairment (r = 0.331, P = 0.005). SLEDAI correlated with GCDs, and attentional and executive domains; SLICC correlated with GCDs, and with visuospatial and attentional domains impairment. CONCLUSIONS: Anti-phospholipids, disease activity, and chronic damage are associated with cognitive dysfunction in SLE. The use of a wide spectrum of tests allowed for a better selection of the relevant factors involved in SLE cognitive dysfunction, and standardized neuropsychological testing methods should be used for routine assessment of SLE patients.

Vaccination and autoimmune rheumatic diseases.

Patients with autoimmune rheumatic diseases are at increased risk of developing infections. However, concerns about the safety and the immunogenicity of vaccines in these patients limited their use. Most of the data against the use of vaccines come from the reported cases of previously healthy individuals who presented the onset of rheumatic diseases after immunization, nevertheless a causal relationship has not been established. During the past few decades influenza and pneumococcal vaccines, administered to patients with systemic lupus erythematosus, were found to be safe and, generally, serologically effective, even though there is the possibility of inadequate response, especially in patients receiving immunosuppressive agents. In patients with rheumatoid arthritis influenza and pneumococcal vaccines can be considered safe and immunogenic in most cases. Treatment with TNFalpha blocking agents did not appear to impair the immune response.