Significant heightened methylation levels of RUNX3 gene promoter in patients with systemic lupus erythematosus.

OBJECTIVE: Researchers are actively investigating new diagnostic and prognostic biomarkers that offer improved sensitivity and specificity for systemic lupus erythematosus (SLE). One area of interest is DNA methylation changes. Previous studies have shown a connection between the RUNX3 gene dysfunction and SLE. In this study, the focus was on examining the methylation level of the RUNX3 promoter in peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy individuals. METHODS: A total of 80 individuals diagnosed with SLE from Iran, along with 77 healthy individuals, were included. The methylation levels of the RUNX3 gene in the extracted DNA were evaluated using the MethyQESD method. To determine the diagnostic effectiveness of the RUNX3 promoter methylation level, a receiver operating characteristic (ROC) curve was generated. RESULTS: The methylation of the RUNX3 promoter was found to be significantly higher in patients with SLE compared to healthy individuals (p < .001). This difference in methylation levels was observed between SLE patients and healthy individuals and between SLE patients with renal involvement and those without renal involvement (86.29 ± 10.30 vs 40.28 ± 24.21, p < .001). ROC analyses revealed that the methylation level of the RUNX3 promoter had a diagnostic power of 0.769 [95% CI (0.681-0.814)] for SLE. Additionally, there was a positive correlation between the RUNX3 methylation level and levels of creatinine and C4. CONCLUSION: The findings of this study emphasize the potential use of RUNX3 methylation levels in PBMCs of SLE patients as biomarkers for diagnosing the disease, predicting renal damage, and assessing disease activity.

Pearls and Pitfalls of Adaptive Optics Ophthalmoscopy in Inherited Retinal Diseases.

Adaptive optics (AO) retinal imaging enables individual photoreceptors to be visualized in the clinical setting. AO imaging can be a powerful clinical tool for detecting photoreceptor degeneration at a cellular level that might be overlooked through conventional structural assessments, such as spectral-domain optical coherence tomography (SD-OCT). Therefore, AO imaging has gained significant interest in the study of photoreceptor degeneration, one of the most common causes of inherited blindness. Growing evidence supports that AO imaging may be useful for diagnosing early-stage retinal dystrophy before it becomes apparent on fundus examination or conventional retinal imaging. In addition, serial AO imaging may detect structural disease progression in early-stage disease over a shorter period compared to SD-OCT. Although AO imaging is gaining popularity as a structural endpoint in clinical trials, the results should be interpreted with caution due to several pitfalls, including the lack of standardized imaging and image analysis protocols, frequent ocular comorbidities that affect image quality, and significant interindividual variation of normal values. Herein, we summarize the current state-of-the-art AO imaging and review its potential applications, limitations, and pitfalls in patients with inherited retinal diseases.

The Inhibitory Effect of Connective Tissue Growth Factor Antibody on Postoperative Fibrosis in a Rabbit Model of Trabeculectomy.

Purpose: To compare the efficacy of subconjunctival injection of an anti-connective tissue growth factor antibody (anti-CTGF) versus mitomycin-C (MMC) and placebo in reducing scar formation in a rabbit model of trabeculectomy. Methods: A total of 14 rabbits were included. Nine rabbits underwent trabeculectomy with subconjunctival injections of either anti-CTGF antibody, MMC, or balanced salt solution (BSS), each administered in three eyes, before peritomy. The anti-CTGF group received a repeated dose of the antibody five days after surgery. All nine rabbits were euthanized on day 14; the globes were stained with hematoxylin & eosin, Masson's Trichrome, and immunohistochemistry for detecting alpha-smooth muscle (α-SMA) actin. RNA extraction was performed on five eyes of the remaining rabbits which included one eye without any surgery, one eye 5 hr after trabeculectomy without any injection, one eye five days after trabeculectomy without any injection, and two eyes five days after trabeculectomy with administration of MMC and BSS, respectively. Results: The mean bleb area in the anti-CTGF, MMC, and control groups was 3.8 ± 1.45, 5.9 ± 1.4, and 3.5 ± 1.9 mm2, respectively. Collagenous tissue was found to occupy the bleb area by 13.7%, 13.5%, and 18.5%, respectively. This ratio was significantly higher in the BSS group (P = 0.04). The expression of CTGF mRNA after 5 hr and five days in eyes undergoing trabeculectomy were significantly more pronounced as compared to the unoperated eye. The mean H-SCORE of α-SMA-immune reactive cells calculated as the grade of staining multiplied by the percentage of immune stained cells was 14.6, 10.22, and 140.58 in the anti-CTGF, MMC, and control groups, respectively. While the control eyes had a significantly higher score (Ps < 0.001), the anti-CTGF and MMC groups were comparable (P = 0.87). Conclusion: Based on the results of this animal study, the anti-CTGF antibody injection resulted in a significant reduction in collagenous tissue and myofibroblast cells after trabeculectomy.

Choroidal Thickness in Different Types of Inherited Retinal Dystrophies.

PURPOSE: To compare the choroidal thickness among eyes with retinitis pigmentosa (RP), Stargardt disease, Usher syndrome, cone-rod dystrophy, and healthy eyes of sex- and age-matched individuals. METHODS: In this comparative study, 503 eyes with RP (n = 264), cone-rod dystrophy (n = 109), Stargardt disease (n = 76), and Usher syndrome (n = 54) were included. To validate the data, 109 healthy eyes of 56 sex- and age-matched individuals were studied as controls. Choroidal imaging was performed using enhanced depth imaging-optical coherence tomography. Choroidal thickness was measured manually using MATLAB software at 13 points in nasal and temporal directions from the foveal center with the interval of 500 µm and the choroidal area encompassing the measured points was calculated automatically. RESULTS: The mean age was 36.33 ± 13.07 years (range, 5 to 72 years). The mean choroidal thickness at 13 points of the control eyes was statistically significantly higher than that in eyes with RP (P < 0.001) and Usher syndrome (P < 0.05), but not significantly different from that in eyes with Stargardt disease and cone-rod dystrophy. Among different inherited retinal dystrophies (IRDs), the choroidal thickness was the lowest in eyes with RP (P < 0.001). Choroidal thickness in the subfoveal area correlated negatively with best-corrected visual acuity (r = - 0.264, P < 0.001) and the duration of ocular symptoms (r = - 0.341, P < 0.001) in all studied IRDs. No significant correlation was observed between the subfoveal choroidal thickness and central macular thickness (r = - 0.24, P = 0.576). CONCLUSION: Choroidal thinning in four different types of IRDs does not follow a similar pattern and depends on the type of IRD and the duration of ocular symptoms. A larger cohort is required to verify these findings.

An Evaluation on Iran International Public Health Summer School in Relation to its Efficacy Based on Participants' Experience and Opinions.

BACKGROUND: A serious challenge to educate health staff for public health is to appear encouraging enough to persuade them for learning issues on this field and implementing new educational methods and innovative ways. Iran International Public Health Summer School (IPHS) made an effort to provide medical sciences students with a fortune to get familiar with and involved in public health. This study intended to evaluate the efficacy of this event. MATERIALS AND METHODS: This cross-sectional study was performed in March-April 2015 by the help of an electronic self-administered questionnaire filled out by 49 Iranian participants 6 months after IPHS2014. The questionnaire assessed the main goals in seven main domains: Interest, activities, and general knowledge in the field of public health, general skills, educational methods, educational and executive schedules, and general satisfaction. RESULTS: Average scores of all domains were >3 (the mean), and all were statistically significant. The highest average score belonged to educational methods (3.92) and the lowest was calculated for the item regarding participants' activities on public health (3.5). No significant difference was found between positive answers of individuals who were interested or active in public health prior to the event and those who had no background. CONCLUSIONS: We believe IPHS was a unique instance in Public Health Education in Iran. Considering the level of success of this program to reach its goals for both students' with or without any previous background on public health, it is recommended as a general model to be simulated in other developing countries.

The effect of salsalate on biochemical factors and endothelial dysfunction of prediabetic patients: A randomized clinical trial.

BACKGROUND: The beneficial effect of using nonacetylated salicylates such as salsalate on decreasing the speed of diabetes progression is a controversial issue. The aim of this study was to evaluate the effect of salsalate on metabolic-syndrome-associated parameters as well as the endothelial function of diabetic and impaired glucose tolerance patients. MATERIALS AND METHODS: Patients were collected from Isfahan endocrinology research center referrals. Patients with impaired glucose tolerance diagnosis or newly diagnosed diabetes were enrolled in the study. Patients were randomized to receive 1.5 g salsalate (2 × 750 mg) BID or placebo twice a day for 3 months. After the mentioned period, all patients were recalled and complete examination was done; blood samples for biochemistry measurements were drawn (for measuring FBS, post prandial glucose, HbA1C, Total cholesterol, HDL, TG, LDL) and forearm flow-mediated dilation (FMD) was performed. RESULTS: Forty patients were enrolled, 32 patients (80%) were female. Mean age of patients was 47.15 ± 6.67 years. FBS (fasting blood sugar) was shown to be significantly different between intervention and control subjects before or after treatment. FMD increased significantly in the intervention group (P = 0.004). CONCLUSION: The study showed that salsalate decreased FBS levels of patients. It may also improve endothelial function as FMD increased significantly in the intervention group.

Effect of particulate air pollution and passive smoking on surrogate biomarkers of endothelial dysfunction in healthy children.

BACKGROUND: This study aimed to determine the association of ambient particulate matter (PM) on surrogate markers of endothelial function and inflammation in healthy children with or without exposure to second-hand smoke. METHODS: This cross-sectional study was conducted in 2011 in Isfahan, which is the second largest and second most air-polluted city in Iran. The areas of the city with lowest and highest air pollution were determined, and in each area, 25 pre-pubescent boys with or without exposure to daily tobacco smoke at home were selected, i.e. 100 children were studied in total. Serum levels of C-reactive protein (CRP) and nitric oxide (NO) were measured. RESULTS: Mean (SD) NO concentration was 7·87 (2·18) and 7·75 (2·04) µmol/L for participants not exposed and exposed to passive smoking, respectively, which is not statistically significant. The corresponding figures for CRP concentrations were 1·69 (0·89) and 2·13 (1·19) µg/ml (P = 0·04). Mean (SD) CRP concentration was significantly higher in children living in the highly polluted area than in those in the area of low pollution [2·11 (1·91) vs 1·60 (1·43) µg/ml, respectively, P = 0·02]. This difference was not significant for NO concentration. The regression analysis that examined the association between PM concentration (as independent variable) and CRP and NO levels (as dependent variables) in children not exposed to passive smoking demonstrated that increased PM was associated with a decrease in NO and an increase in CRP concentration. This finding shows that, regardless of passive smoking, PM10 concentration has a significant independent association with serum CRP and is inversely associated with NO levels. CONCLUSION: The findings suggest that in healthy children PM concentration has a significant independent association with biomarkers of endothelial dysfunction and inflammation.

National report on the association of serum vitamin D with cardiometabolic risk factors in the pediatric population of the Middle East and North Africa (MENA): the CASPIAN-III Study.

OBJECTIVES: As the first, to our knowledge, nationwide study in the Middle East and North Africa (MENA), this study aimed to investigate the association of serum 25 hydroxy vitamin D [25(OH)D] levels with cardiometabolic risk factors in a nationally representative sample of the pediatric population in Iran. The second objective was to provide the prevalence of hypovitaminosis D and the percentiles of serum 25(OH)D in the study population. METHODS: This national population-based study was conducted among 1100 Iranian students living in 27 provinces in Iran. The association of 25(OH)D with each cardiometabolic risk factor was determined after adjustment for age, gender, body mass index, and waist circumference. RESULTS: Participants consisted of 1095 students (52% boys) with a mean age of 14.74 ± 2.61 y. The median 25(OH)D level corresponded to a vitamin D insufficiency level: 12.70 ng/mL in boys and 13.20 ng/mL in girls. Overall, 40% of participants were vitamin D deficient, and 39% had vitamin D insufficiency. There were no significant differences in these findings between boys and girls. Adjusted regression analysis revealed a significant weak inverse association of 25(OH)D with systolic blood pressure, diastolic blood pressure, total cholesterol, and low-density lipoprotein cholesterol. This association was significantly positive with high-density lipoprotein cholesterol, but not with fasting plasma glucose and metabolic syndrome. CONCLUSION: We found a considerably high prevalence of hypovitaminosis D in the pediatric population of a sunny region. Our findings also revealed an association of hypovitaminosis D with many cardiometabolic risk factors from childhood; these associations were independent of obesity indexes. It is of special concern that the highly prevalent disorders of low 25(OH)D and low high-density lipoprotein cholesterol in children and adolescents of the MENA region had significant association. The clinical importance of our findings needs to be confirmed in longitudinal studies.

Body Mass Index, Weight-for-age, and Stature-for-age Indices in Iranian School Children in Relation to Weight and Growth Disorders: A Population-based Survey.

BACKGROUND: Present study aimed to evaluate the prevalence of grades of nutritional status comprising underweight, normal weight, overweight, and obesity as well as other measurable anthropometric indicators of body mass index (BMI) in regard to gender, educational level, and living area among students settled in Isfahan province. METHODS: This cross-sectional study was conducted on a sample of 4700 individuals (2349 females and 2351 males) being from 9 to 15 years old, while they were students of either primary school or junior high school. Random cluster method was applied in both urban (84%) and rural (16%) areas of Isfahan province. BMI values were measured and then categorized using reference growth charts from the Centers for Disease Control and Prevention (CDC 2000). Weight-for-age and stature-for-age indices were assessed as well in accordance with CDC growth charts. RESULTS: The overall prevalence of underweight, overweight, and obesity was 13.9, 10.4, and 5.7%, respectively. Boys and students of urban areas showed a higher tendency of obesity and overweight in comparison with girls and rural students respectively. Furthermore, rural students had poorer status in both weight-for-age and stature-for-age indices. In addition, educational level was the only statistically efficacious factor. CONCLUSIONS: This study and previous ones demonstrated that children and adolescents' nutritional status, which strongly affect general health status of individuals, should receive more exquisite attention.

Nutritional Knowledge, Practice, and Dietary Habits among school Children and Adolescents.

BACKGROUND: Although nutritional status of children and adolescents is of great concern various interventions and modifications aiming at promotion of healthy eating behaviors have limited impact due to insufficient understanding of dietary habits between different age groups and genders. The aim of this study in not only evaluation of nutritional knowledge, practice, and dietary habits of primary school and junior high school students in Isfahan province, but also this research explore crucial differences regarding gender and living area of the above-mentioned population in Iran. METHODS: This cross-sectional study was conducted on 4700 primary school and junior high school pupils in Isfahan province. Data were collected through standard 24-h recall food frequency questionnaire and researcher-designed questionnaire. Independent t-test was applied for comparison of mean values of total units of consumed food materials. Qualitative variables were compared by using the Chi-square test. Data were analyzed by ACCESS 2010 and SPSS 18 software. RESULTS: Nutritional knowledge of female pupils and junior high school students was higher than their male and elementary school students respectively; still, theses superiorities did not lead to higher practice score. Bread and cereals group received daily intakes in accordance with food and drug administration (FDA) recommendations. Indeed, vegetables, milk, and dairy products, as well as meat daily intakes, were lower than the FDA recommendation, whereas fats, oils, and sugars intakes were higher. In comparison to females, male participants had significantly lower consumption of vegetables and fruits whilst they had a higher intake of carbohydrates, fats, and meats. CONCLUSIONS: Our results showed that adolescents failed to meet sufficient nutritional requirements, and they had an imbalanced diet, which was considerably low in several essential nutrients and high in some food materials.