Evaluation of survivin expression and regulating miRNAs of survivin expression in peripheral blood mononuclear cells in systemic lupus erythematous patients.

BACKGROUND: Systemic lupus erythematosus is a multisystemic rheumatic disease with different clinical features. Disturbance in apoptosis regulation seems to be a major factor in SLE development. OBJECTIVE: Survivin plays a key role in mitosis and inhibiting apoptosis. A study was conducted to examine the expression level of survivin and miRNAs that affect survivin transcript levels in patients with SLE. METHODS: We isolated peripheral blood mononuclear cells from 50 inactive SLE patients and 50 healthy controls. RNA is extracted and converted to cDNA. The quantitative real-time polymerase chain reaction is conducted to assess the expression levels of survivin total and its variants with effective miRNAs in PBMCs. RESULTS: Expression levels of miR-34a-5p (fold change = 1.5, p++ = 0.027), and 218-5p (fold change = 1.5, p++ = 0.020) were significantly increased. While miR-150-5p (fold change = 0.56, p++ = 0.003) was significantly decreased. The mRNA expression of survivin-WT (fold change = 0.63, p++ = 0.002) was significantly downregulated in SLE patients compared to the healthy controls. Survivin total and its two major variants (survivin-2B, and survivin-ΔEx3) did not differ significantly between SLE patients and controls. CONCLUSION: Although survivin-TS and its two variants (survivin-2B, and survivin-ΔEx3) were not differently expressed in SLE patients, survivin-WT had altered expression. Despite aberrant miRNA expression in PBMCs from SLE patients, survivin and miRNA expression were not associated with leukopenia. The pathogenesis of SLE disorder might be linked to survivin's other roles in the immune system aside from anti-apoptotic functions.

Reliability, validity, and cultural adaptation of the Persian version of the Exercise Adherence Rating Scale (EARS) in patients with knee osteoarthritis.

OBJECTIVES: The aim of this study was to culturally adapt and assess the validity and reliability of the Exercise Adherence Rating Scale (EARS) in Persian language for patients with knee osteoarthritis. METHODS: The original English version of the EARS was forward-translated to Persian (by an expert and a non-expert in the field of exercise and health science) and then backward-translated to English by two people, and then by a committee of five, pre-final Persian version of EARS was created. Patients were provided with a three-month exercise program, three times a week, through telerehabilitation. After completion of the exercise program, patients filled out the Persian version of EARS and the Scanlan questionnaire. Three weeks later, patients completed the EARS and Scanlan questionnaire again. During the study, patients recorded the number of exercise sessions weekly in a standardized diary form. Face validity was assessed by ten patients, using the item impact method. Content validity was assessed by five experts and quantified using the content validity ratio and content validity index. Agreement between EARS and Scanlan questionnaire was assessed using Spearman test and Bland-Altman plot. The reliability of the Persian version of EARS was assessed using the intraclass correlation coefficient and Cronbach's α. RESULTS: A total of 30 patients (3 men, 27 women), with a mean age of 59 years (SD â€‹= â€‹10), participated in this study. All items of the Persian version of EARS had item impact method scores above 1.5, indicating acceptable face validity. The scale-content validity index/average for relevancy and simplicity components were calculated as 0.87 and 0.85, respectively, indicating good content validity. Bland-Altman plot showed good agreement between EARS and Scanlan questionnaire at baseline and three weeks later. Cronbach's alpha was 0.96, indicating excellent internal consistency. The intraclass correlation coefficient (95% CI) was 0.996 (0.991, 0.998), indicating excellent reliability. CONCLUSIONS: The Persian version of EARS demonstrated acceptable cultural adaptation, reliability, and validity in patients with knee osteoarthritis. The use of the Persian version of EARS can be a reliable and valid tool to assess exercise adherence in patients with knee osteoarthritis. LEVEL OF THE EVIDENCE: II.

Comparative analysis of mental workload and performance between young and elderly drivers: Implications for road safety and age-related driving challenges.

BACKGROUND: Driving represents a multifaceted cognitive endeavor, demanding heightened vigilance and swift responses. Considering the high statistics of driving accidents and heavy loads, as well as the effect of the driver's age on the occurrence of accidents, it is important to investigate these factors to reduce accidents. OBJECTIVE: This study investigates the impact of mental workload on the performance of young and older drivers in a dynamic driving scenario to compare cognitive performance, workload perception, and driving outcomes between the two age groups. METHODS: Cognitive tests including the Stroop test, Continuous Performance test, and Focused Attention test were conducted, alongside the use of the DALI questionnaire to measure workload levels. Participants encompassed twenty male drivers, divided into two age groups: 20 to 35 years and 55 to 70 years, with varying years of driving experience. The study entailed a dynamic driving scenario involving a designated route in Tehran, Iran. RESULTS: Results exhibited differences in workload scores between the age groups, particularly in dimensions such as visual demand, auditory demand, attention, and interference. Older drivers demonstrated heightened cognitive and physical demands during driving, implying a greater need for attention and cognitive effort. CONCLUSION: The findings of this study indicated that navigating through congested roads and dense urban traffic significantly elevates the mental workload for drivers, consequently impacting their cognitive functioning. Given the critical need for attention in driving, this heightened workload can manifest as increased fatigue, increasing stress levels, and diminished concentration, all of which substantially raise the risk of vehicular accidents. Furthermore, the study highlighted a particular concern for older drivers, whose diminished cognitive capacities further raise their vulnerability to accidents under such demanding driving conditions.

Determination of IL-23 receptor expression and gene polymorphism (rs1884444) in Iranian patients with ankylosing spondylitis.

BACKGROUND: Through investigating genetic variations, it has been demonstrated that single nucleotide polymorphisms (SNPs) in the IL-23 receptor (IL23R) gene have a critical role in the pathophysiology of ankylosing spondylitis (AS). Here, we investigated whether the IL23R variant (rs1884444) is associated with AS in the Iranian population. METHODS AND MATERIAL: In this research, we analyzed rs1884444 in a group of 425 patients with AS and 400 matched controls. For DNA extraction, the phenol/chloroform technique was utilized. Peripheral blood mononuclear cells (PBMCs) were obtained from the whole blood of 39 patients and 43 healthy controls and total RNA was extracted. Genotyping was performed by amplification-refractory mutation system (ARMS)-PCR method. Afterward, the expression level of IL23R was analyzed by the real-time quantitative (Q)-PCR method. RESULTS: We observed no significant association between the distribution of alleles and genotypes of rs1884444 and susceptibility to AS. In addition, the expression level of IL23R did not differ between PBMCs from AS patients compared to the control group (P = 0.167). Furthermore, the relative expression level of IL23R was positively correlated with the BASDAI (P < 0.01) and BASFI (P < 0.05) scores of the patients. CONCLUSION: It appears that IL23R polymorphism (rs1884444) and the level of gene expression might not contribute to the susceptibility to AS in the Iranian population. The correlation of IL23R expression with the level of BASDAI and BASFI scores in patients may be due to the role of the IL-23/IL-23R signaling cascade in inflammation and exert a critical role in the development of AS.

Interferon-γ Induces Interleukin-6 Production and Alpha-smooth Muscle Actin Expression in Systemic Sclerosis Fibroblasts.

Systemic sclerosis (SSc) is an autoimmune systemic disease that is characterized by immune dysregulation, inflammation, vasculopathy, and fibrosis. Tissue fibrosis plays an important role in SSc and can affect several organs such as the dermis, lungs, and heart. Dysregulation of interferon (IFN) signaling contributes to the SSc pathogenesis and interferon regulatory factor 1 (IRF1) has been indicated as the main regulator of type I IFN. This study aimed to clarify the effect of IFN-gamma (-γ) and dexamethasone (DEX) on the IRF1, extracellular signal-regulated kinase 1/2 (ERK1/2), and the expression of alpha-smooth muscle actin (α-SMA) in myofibroblasts and genes involved in the inflammation and fibrosis processes in early diffuse cutaneous systemic sclerosis (dcSSc). A total of 10 early dcSSc patients (diffuse cutaneous form) and 10 unaffected control dermis biopsies were obtained to determine IFNγ and DEX effects on inflammation and fibrosis. Fibroblasts were treated with IFNγ and DEX at optimum time and dose. The expression level of genes and proteins involved in the fibrosis and inflammation processes have been quantified by quantitative real-time PCR (RT-qPCR) and western blot, respectively. IFNγ could up-regulate some of the inflammation-related genes (Interleukin-6; IL6) and down-regulate some of the fibrosis-related genes (COL1A1) in cultured fibroblasts of patients with early dcSSc compared to the untreated group. Besides, it has been revealed that IFNγ can induce fibroblast differentiation to the myofibroblast that expresses α-SMA. Concerning the inhibitory effect of IFNγ on some fibrotic genes and its positive effect on the inflammatory genes and myofibroblast differentiation, it seems that IFNγ may play a dual role in SSc.

Regional fat distribution and hepatic fibrosis and steatosis severity in patients with nonalcoholic fatty liver disease and type 2 diabetes.

Background: Epidemiologic findings suggest that measures of body fat distribution predict health outcomes independent of the overall body fat assessed by body mass index (BMI). This study aimed to evaluate the associations of overall and regional body fat with the severity of hepatic steatosis and fibrosis in type 2 diabetic patients with non-alcoholic fatty liver disease. Methods: Bioelectric impedance analysis and two newly developed anthropometric indices, namely, A Body Shape Index (ABSI) and Body Roundness Index (BRI), were used to estimate the body fat. Based on fibroscan parameters, significant hepatic fibrosis and severe steatosis were defined as ≥F2 and >66%, respectively. Results: Higher total body fat (odds ratio [OR] 1.107, 95% confidence intervals (CI) 1.038-1.182, p = 0.002), trunk fat (OR 1.136, 95% CI 1.034-1.248, p = 0.008) and leg fat (OR 1.381, 95% CI 1.139-1.674, p = 0.001) were associated with liver fibrosis. However, in contrast to the total body fat (OR 1.088, 95% CI 1.017-1.164, p = 0.014) and leg fat (OR 1.317, 95% CI 1.066-1.628, p = 0.011), the trunk fat was not associated with severe hepatic steatosis. BRI performed better than trunk, leg and total body fat in predicting hepatic steatosis (OR 2.186, 95% CI 1.370-3.487, p = 0.001) and fibrosis (OR 2.132, 95% CI 1.419-3.204, p < 0.001). Moreover, the trunk to leg fat ratio and ABSI were not independent predictors of either steatosis or fibrosis (p > 0.05). Conclusion: BRI revealed a superior predictive ability for identifying the degree of hepatic steatosis and stiffness than other obesity indices. Additionally, higher levels of adiposity in the trunk, legs, and overall body were linked to an increased risk of developing liver fibrosis. Although trunk fat did not show an association with severe hepatic steatosis, an increase in leg and total fat was related to liver steatosis.

The investigation of killer-cell immunoglobulin-like receptors (KIRs) and their HLA ligands in Iranian patients with myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) is a disabling disease with the underlying pathophysiology of auto-antibodies attacking the postsynaptic acetylcholine receptors of neuromuscular junctions causing muscle weakness. Natural killer (NK) cells are innate immune cells that play an important regulative role in immune responses. The human killer-cell immunoglobulin-like receptors (KIRs) family is one of the receptors on NK cells that can either activate or inhibit NK cells. This study aimed to assess the possible role of KIR and their human leukocyte antigen (HLA) ligand genes susceptibility to MG in Iranian patients. METHOD: One hundred and sixty-three patients with MG diagnosis based on the presence of clinical symptoms and laboratory tests and 400 healthy volunteers were studied. We used the polymerase chain reaction (PCR) technique for genotyping 15 KIRs and 5 HLA genes. RESULTS: The results demonstrated that there was no significant difference in the frequency of KIR genes and inhibitory KIR genotypes between controls and patients. In MG patients, HLA-C1Asn80 was significantly less frequent than in matched controls. The frequency of HLA genotype number 7 was significantly lower in MG cases, compared to the controls. Analysis of activating KIR genotypes showed that genotype number 10 was significantly less frequent in MG cases than in matched controls. CONCLUSION: Our results suggest that the presence HLA-C1Asn80 might play a protective role against the pathogenesis of MG. The significantly decreased prevalence of one activating KIR genotype and one of the HLA genotypes in MG cases suggest that these genotypes can reduce the risk of MG development. To specifically reveal the impact of KIR and HLA in MG, more studies are required.