Highlighting allelic variations at the interleukin-19 locus in term of preeclampsia predisposing factors and access to an accurate diagnostic/screening option.

BACKGROUND: Preeclampsia is the main cause of preterm parturition and maternal-fetal complications. T helper 1 and T helper 2 cytokines balance is a requirement in normal pregnancy and aberrant in this immunologic balance, play an important role in the pathology of preeclampsia. In previous studies single nucleotide polymorphisms have been associated with the alteration of serum cytokine levels. OBJECTIVE: This study was aimed to discover association between interleukin-13 (rs20541, and rs56035208) and interleukin-19 (rs1028181 (T/C) and rs2243191(T/C)) polymorphisms with susceptibility to preeclampsia. METHODS: In this case-control study 300 women with and without preeclampsia (n = 150/each) who referred to Zeynabieh Hospital- Shiraz, Iran, from February 2021 to April 2022 were enrolled. For genotyping the interleukin-13 and interleukin-19 polymorphisms, the Allele-specific polymerase chain reaction and direct sequencing method was carried out. RESULTS: Our statistical results revealed no significant differences in allele and genotype frequencies for interleukin-13 polymorphisms compared to controls. We found that the interleukin-13 polymorphisms are significantly associated with vulnerability to edema at rs20541 position and maternal drinking at rs56035208 position. But it was interesting to note that the differences of both the allele and genotype frequencies of interleukin-19 polymorphisms and their contribution to the risk of preeclampsia susceptibility were significant. CONCLUSIONS: No risk of preeclampsia was found in all comparisons for interleukin-13 polymorphisms. However, the interleukin-19 polymorphisms were found to confer the risk of preeclampsia in our population.

Spontaneous miscarriage driven by maternal genetic mutation at position of PAI-1-844G/A: shed light on a race-specific genetic polymorphism.

OBJECTIVE: Association between a genetic polymorphism and disease, either positively or negatively, within a population may not necessarily predict association in other race-ethnic populations. The aim of this study was to genotype well recognized thrombophilia associated polymorphisms as common risk factors for miscarriage and investigate their benefit to use as risk factors in southwest region of Iran females (Khuzestan) in the Arabs ethnic minority group with spontaneous miscarriage. We developed a Reverse Dot Blot Assay for the genotyping of four polymorphisms. RESULTS: There were significant differences in the genotype distribution and allelic frequencies of the MTHFR 1298 A > C, MTHFR 677 C > T, Factor V Leiden 1691 G > A, PAI-1-844G > A polymorphisms between the case and control groups. The MTHFR 1298 A > C, MTHFR 677 C > T and Factor V Leiden 1691 G > A polymorphisms were significantly associated with spontaneous miscarriage risk. Unlike some other race-ethnic populations, PAI-1-844G > A polymorphism was associated with risk of developing unplanned miscarriage in Iranian Arabs ethnic minority group females.

Crucial Role of Foxp3 Gene Expression and Mutation in Systemic Lupus Erythematosus, Inferred from Computational and Experimental Approaches.

The impaired suppressive function of regulatory T cells is well-understood in systemic lupus erythematosus. This is likely due to changes in Foxp3 expression that are crucial for regulatory T-cell stability and function. There are a few reports on the correlation between the Foxp3 altered expression level and single-nucleotide polymorphisms within the Foxp3 locus. Moreover, some studies showed the importance of Foxp3 expression in the same diseases. Therefore, to explore the possible effects of single-nucleotide polymorphisms, here, we evaluated the association of IVS9+459/rs2280883 (T>C) and -2383/rs3761549 (C>T) Foxp3 polymorphisms with systemic lupus erythematosus. Moreover, through machine-learning and deep-learning methods, we assessed the connection of the expression level of the gene with the disease. Single-nucleotide polymorphisms of Foxp3 (IVS9+459/rs2280883 (T>C) and -2383/rs3761549 (C>T)) were, respectively, genotyped using allele-specific PCR and direct sequencing and polymerase chain reaction-restriction fragment length polymorphism, in 199 systemic lupus erythematosus patients and 206 healthy age- and sex-matched controls. The Statistical Package for the Social Sciences version 19 and Fisher's exact and chi-square tests were used to analyze the data. Moreover, six machine-learning models and two sequential deep-learning models were designed to classify patients from normal people in the E-MTAB-11191 dataset through the expression level of Foxp3 and its correlated genes. The allele and genotype frequencies of both polymorphisms in question were found to be significantly associated with an increased risk of systemic lupus erythematosus. Furthermore, both of the two single-nucleotide polymorphisms were associated with some systemic-lupus-erythematosus-related risk factors. Three SVM models and the logistic regression model showed an 81% accuracy in classification problems. In addition, the first deep-learning model showed an 83% and 89% accuracy for the training and validation data, respectively, while the second model had an 85% and 79% accuracy for the training and validation datasets. In this study, we are prompted to represent the predisposing loci for systemic lupus erythematosus pathogenesis and strived to provide evidence-based support to the application of machine learning for the identification of systemic lupus erythematosus. It is predicted that the recruiting of machine-learning algorithms with the simultaneous measurement of the applied single nucleotide polymorphisms will increased the diagnostic accuracy of systemic lupus erythematosus, which will be very helpful in providing sufficient predictive value about individual subjects with systemic lupus erythematosus.

Predisposition to Myocardial Infarction Influenced by Interleukin 13 Gene Polymorphisms: A Case-Control Study.

BACKGROUND: Additional inflammatory responses and subsequent damage-arising from enhance transcriptional activity or forming the more active protein due to existence of polymorphic sites in the pro-inflammatory cytokines gene loci-give rise to myocardial infarction susceptibility. OBJECTIVES: The aim of our study was to explore whether two interleukin-13 gene polymorphisms (-1512A/C and +2044G/A) could serve as underpins genetic susceptibility of myocardial infarction. METHODS: The Iranian population that belong to the Parsis ethnic group was involved in the present study. A total 250 patients with definite myocardial infarction-meeting hypertension, hypercholesterolemia, hyperglycemia, and coronary artery disease requirements-were recruited from the Shiraz urban hospitals. 250 age- and sex-matched healthy individuals without a history of cardiovascular disease and heart disease related risk factors constituted the control group. PCR-restriction fragment length polymorphism technique applied to genotyping at -1512A/C and +2044G/A loci. Hardy-Weinberg equilibrium test was performed (combined cases and controls). The differences of the genotype frequencies in cases and controls were analyzed using a chi-square test. Logistic regression analysis was performed to assess the association between the genotypes and most important risk factors for myocardial infarction. All statistical analyses were performed in SPSS Version 22.0. p-values below 0.05 were hailed as statistically significant. RESULTS: Deviation from Hardy-Weinberg equilibrium was not significant in the -1512A/C locus. Statistically significant difference between our study groups was found in genotype frequency of the -1512A/C. This variant was found in associated with myocardial infarction risk factors. The +2044G/A polymorphism was not in Hardy-Weinberg equilibrium and no significant difference observed in the distribution of +2044G/A genotype frequency among cases and controls. However, further analysis revealed that this genotype associated with an increased susceptibility to myocardial infarction risk factors. CONCLUSIONS: The presence of interleukin-13 -1512A/C and +2044G/A gene polymorphisms underpin myocardial infarction predisposition in the ethnic Parsis of the Iranian population.

Turning unprofessional behaviors around using Holmes' reflection approach: a randomized controlled study.

Many medical schools around the world have included professionalism training in their formal curriculum. However, these efforts may not be adequate; given the exposure of students to unprofessional behaviors in the clinical settings. In the present study, we aimed to design, implement, and evaluate a longitudinal program to improve professionalism among medical students upon their transition to clinical settings. A total of 75 medical students were enrolled in the study and randomly assigned to two groups. The control group did not receive any training, while for the intervention group; a 10-hour program through 16 weeks was organized based on the Holmes' reflection approach. The effectiveness of the program was evaluated by measuring three outcomes in both groups. Data analysis was performed using paired t-test and Multiple Linear Regression. Scores of judgment of professionalism increased in the intervention group (from 7.56 to 10.17; P< 0.001), while there was no significant improvement in the control group's scores. Students' attitudes towards professionalism and their professional behaviors did not change significantly. Based on our findings, the Holmes reflection approach helps students improve their cognitive base of professionalism. Long-term follow-up and further qualitative studies will help us better understand the effects of this approach on other desirable outcomes.

Validating Self-Reflection and Insight Scale to Measure readiness for Self-Regulated Learning.

BACKGROUND: Professional behavior of physicians is under scrutiny by medical associations, media, and patients; therefore, medical students are expected to be self-directed learners rather than the passive ones. One of the useful strategies for professional development and life-long learning of students is self-regulated learning. Self-regulation concept and lifelong learning commitment are in the heart of medical practice. Therefore, this study aimed to evaluate the validity of Self-Reflection and Insight Scale (SRIS) to inspect the medical students' readiness for self-regulation. MATERIALS AND METHODS: SRIS was translated according to the Sousa and Rojjanasrirat guideline. To examine the reliability and validity evidence of the scale, 136 medical students from Tehran University of Medical Sciences completed the questionnaire. Internal consistency and intraclass correlation were used to examine the reliability evidence, as well as qualitative content validity, and confirmatory factor analysis and exploratory factor analysis (EFA) were used to examine the construct validity of the scale. RESULTS: The content validity of the scale was verified. Cronbach's alpha and the Interclass Correlation Coefficient value for the four-factor model was 0.87 and 0.79, respectively. Goodness-of-fit indices displayed acceptable and poor values (P = 0.0001, χ2 = 373.51, df = 167, Root Mean Square Error Of Approximation = 0.096, standardized root mean square residual = 0.12). EFA was conducted; a well-structured model was achieved through the EFA. The new four-factor model was extracted as the best model by performing EFA. CONCLUSION: SRIS Persian version is saturated with four factors and has desirable content validity and constructs reliability.