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Abstract Background Despite all the advances in our knowledge regarding obesity, our understanding of its etiology is still far from complete. This study aimed to evaluate the association of serum irisin levels with physical activity and some of the metabolic syndrome-related biomarkers among obese people with low-calorie intake and non-obese people with high-calorie intake. Methods Obese and non-obese healthy individuals with respectively low and high-calorie intakes were recruited. Irisin and other biomarkers were measured using standard biochemical methods. Participants’ physical activity was evaluated by administering the International Physical Activity Questionnaire (IPAQ). To analyze the body composition of the participants, a standard body composition device (ioi 353) was applied. Logistic regression was used to calculate the odds ratio (OR) and to examine the effect of confounders such as age, sex, genetics, and activity. Results Data from the seventy-seven participants were included in the final analysis. The mean age of the participants in the obese and non-obese groups was 38.33 ± 14.88 and 30.24 ± 13.37 years, respectively. Participants in the obese group had lower physical activity compared to the non-obese group (3395.38 ± 2801 MET-min/week vs. 6015.18 ± 3178 MET-min/week; p

Abstract Background: Recurrent pregnancy loss (RPL) creates complex reproductive conditions among women. Problem-solving therapy is one of the sexual health approaches. Objective: This study was designed to investigate the effect of online problem-solving counseling on the sexual anxiety and intimacy of women with RPL. Materials and Methods: A randomized clinical trial was conducted at Abortion Research Center in Yazd, Iran between March and August 2023. A total of 70 women with RPL were assigned into 2 groups, that is, intervention and control using random allocation software (n = 35/each). The intervention group received 8 sessions of sexual counseling on problem solving. The control group received an educational pamphlet. The primary outcome was sexual anxiety, and the secondary outcome was sexual intimacy. The data were collected using questionnaires based on sexual anxiety and intimacy. The questionnaires were completed before, after, and 1 month after the study. Results: A total of 70 participants were included in the final analysis. The mean score of sexual anxiety in the 8 th and 12 th wk was significantly less in the online group than in control group (p < 0.001). The mean score of sexual intimacy in the 8 th and 12 th wk was significantly higher in the online group than in control group (p < 0.001). Conclusion: Problem-solving-based sexual health counseling programs may improve sexual anxiety and intimacy in women with RPL. It is recommended to use a sexual health counseling method in RPL centers when considering the effectiveness of this type of training.

Abstract Background: Recurrent miscarriage is one of the most prevalent reproductive diseases. This phenomenon has several reasons, including maternal, hormonal, immunological, and parental genetic factors. Idiopathic recurrent miscarriage (IRM), with no distinctive etiology, involves about half of the recurrent miscarriage cases. Some mutations in mitochondrial DNA can lead to miscarriage. Mitochondrial tRNA (mt-tRNA) mutations cause nearly half of the mitochondrial disorders. Objective: To identify mt- tRNA C y s & T y r gene mutations in Iranian women with IRM. Materials and Methods: In this case-control study, 100 Iranian women with IRM and 100 women as control without any history of miscarriage were investigated by polymerase chain reaction-single strand conformation polymorphism technique followed by gene sequencing. Bioinformatics analysis were done using human mitochondrial genome database, molecular evolutionary genetics analysis, mammalian mitochondrial-tRNA, etc. Results: Results showed 4 mt-tRNA mutations including 1 cysteine mt-tRNA mutation (5824C > T) and 3 tyrosine mt-tRNA mutations (5868T > A, 5849C > T, and 5836T > C) in our cases. Conclusion: Amongst the 4 mutations found, one was novel that is still not reported. Our bioinformatics analysis revealed that these mutations can be pathogenic. They occurred in tRNA-conserved regions and their secondary structure was changed, which can result in mitochondrial dysfunction. Mutations of these genes may help in the assessment of IRM. Further study of all 22 mt-tRNAs possible mutations is recommended to describe their etiologic role in IRM.

Background: Cesarean scar pregnancy (CSP) is a rare long-term complication after cesarean delivery. In clinical practice, its diagnosis and management is very important because it may be associated with serious consequences. Although a wide range of treatment options have been reported, the best treatment is unrecognized yet. This study aimed to evaluate the outcomes of laparoscopy in CSP. Materials and Methods: This non-randomized single-arm clinical trial was conducted on 43 CSP patients who were referred to the educational and medical centers of Isfahan University of Medical Science from 2021 to 2022. All the patients were treated by laparoscopy, and during follow-up, the pregnancy test was measured weekly until the test was negative, and an ultrasound was performed 6 months later. Myometrial thickness and occurrence of isthmocele were checked and recorded. Abnormal uterine bleeding or pelvic pain were also evaluated 6 months later. Results: Mean time of surgery was 55.12 ± 10.61 minutes, and the rate of intraoperative bleeding was 62.93 ± 24.00 cc. Four cases had excess intraoperative bleeding: two of them received packed cells, and two led to laparotomy. After surgery, the time to negative pregnancy test was 19.21 ± 5.50 days and 4 (10.3%) patients had isthmocele in follow-up sonography. Human chorionic gonadotropin hormone (BHCG) decreased significantly after surgery (percentage reduction: 97.71 ± 3.80; P value < 0.001) and myometrial thickness increased significantly (percentage increase: 46.94 ± 28.66; P value < 0.001). Conclusion: Laparoscopic excision of a CSP is an effective and feasible technique with the advantage of an immediate myometrial reconstruction.

Background and Objectives Marriage is one of the effective factors that can promote mental health and lifestyle and reduce the risk of individual and social disorders. This study aims to prioritize the criteria for partner selection according to the perceptions of female students of Qom University of Medical Sciences (QUMS) in 2017. Methods: This is descriptive-analytical study with a cross-sectional design was conducted in 2017. The study population consists of all single female students of QUMS, of whom 373 were selected by multi-stage sampling method. The instrument was the 22-item Preference Criteria of Spouse Selection Inventory (PCSSI) with acceptable validity and reliability. Data were analyzed in SPSS software, version 20 statistical software using descriptive statistics and Friedman’s test, Chi-square test, t-test, and one-way analysis of variance. Results: The age range of the participants was 18-38 years, and their semester range was 1-15. The results of Friedman test showed a significant difference between the mean ranks of partner selection criteria. Mental health had the highest priority, while being from the same ethnicity had the lowest priority. There was a significant negative correlation between age and importance of partner selection criteria (P

Objective(s): Nanotechnology has helped a lot in diagnosing and treating multiple illnesses, specifically cancer, and increasing the development of targeted drug delivery methods. Nanocomposites are materials with at least one component smaller than 100 nm. Therefore, this study aims to assess the anticancer effects of silver-graphene nanocomposite on MCF-7. Materials and Methods: In this study, the rate of inhibition of cancer cell growth and production of reactive oxygen radicals, malondialdehyde, and glutathione stores in MCF7 cells were investigated. Cancer cells were exposed to nano particles for 48 hr. Silver nanoparticles and graphene both reduced the growth rate of MCF-7. Results: Subsequently, by treating the cells with silver-graphene nanocomposite, the rate of inhibition of cell growth at the highest concentration was 84.60%. Nanoparticles also inhibited the growth of cancer cells through the oxidative stress pathway by increasing the amount of intracellular ROS, followed by increasing malondialdehyde and decreasing glutathione stores, so that at the highest combined concentration of nanoparticles, the amounts of LPO and ROS increased up to 70% and 74 %, and glutathione reserves decreased by 16%. Conclusion: Treatment of MCF-7 cells with silver or graphene nanoparticles and combination treatment with these two substances against cisplatin have sound effects, and by affecting oxidative stress factors, such as increased ROS and subsequent increase in lipid membrane damage, inhibit cell growth and proliferation. According to the mathematical model, silver graphene nanocomposite> silver nanoparticles> graphene has the best effect in inhibiting the growth of cancer cells, respectively.

Abstract Background: A large proportion of cases of recurrent pregnancy loss (RPL) are associated with immunological factors. Objective: This study investigated the association between single nucleotide polymorphisms of cytotoxic T-lymphocyte-associated protein (CTLA)-4 gene in women with a history of RPL compared to healthy women. Materials and Methods: A case-control study was performed on 2 groups consisting of 120 healthy women with no history of abortion and at least one delivery (control) and 120 women with a history of 2 or more primary RPLs (case). In addition, 5 mL of peripheral blood sample was taken from all subjects. The frequencies of CTLA-4 rs3087243 and rs231775 polymorphisms were assayed by restriction fragment length polymorphism polymerase chain reaction and rs5742909 using the high-resolution melting real-time polymerase chain reaction method. Results: The mean age of the women in the control and RPL groups were 30.03 ± 4.23 (range 21-37), and 28.64 ± 3.61 yr (range 20-35), respectively. Pregnancy loss numbers ranged between 2-6 in women with a history of RPL, and between 1 and 4 in the successful pregnancy group. Statistical analysis showed a significant difference between the genotypes of GG and AG in the 2 groups in rs3087243 polymorphism (OR 1.00 for GG genotype and OR 2.87 for AG genotype, p = 0.0043). No significant difference was observed in the genotype frequencies of rs231775 and rs5742909 polymorphisms, of the 2 groups (p = 0.37, and p = 0.095), respectively. Conclusion: Our findings indicated that CTLA-4 polymorphism, rs3087243, might be associated with a risk of RPL in Iranian women.

Objective(s): One of the effective strategies for targeted chemotherapy of cancer is the use of lipid nanocarriers. In this study, an optimal formulation of niosomal drug containing doxorubicin was developed to monitor the potency against cancer cells. Materials and Methods: In this experimental study, niosomal vesicles were prepared using phosphatidylcholine (20%), span60 (52.5%), cholesterol (22.5%), and DSPE-PEG2000 (5%) by the thin-film method. Doxorubicin was loaded into the niosomes using an inactive loading method. Results: The features and characteristics of the nanocarrier were evaluated using Zeta-Sizer, SEM, FTIR, drug release, cellular uptake, and the cytotoxicity of the nanodrug carrier system by the MTT method. Niosomal vesicles-containing doxorubicin showed a size of ~156.8 nm, drug encapsulation efficiency of ~94.18%, zeta potential of ~-3.52 mV, and polydispersity index (PDI) of ~0.265. The prepared niosomes indicated a drug-controlled release system and FTIR analysis showed no interaction between nanocarriers containing drug and doxorubicin. Moreover, morphological examination of nanocarriers using SEM microscopy revealed that they had spherical structures. Also, cellular studies showed that drug toxicity was higher in encapsulated form of the drug compared with non-encapsulated doxorubicin which was confirmed by the cellular uptake results. Conclusion: The results confirmed the proper physicochemical characteristics of these nanocarriers that significantly increased the toxicity of the encapsulated drug against the KG-1 cell line. It seems niosomal nanocarriers can be considered suitable carriers for drug delivery to cancer cells.

Objective: To elucidate the possible role of unfractionated heparin in patients with failed repeated in in vitro fertilization and embryo transfer (IVF-ET) and thrombophilia. Methods: This case control study evaluated the efficacy of the unfractionated heparin in increasing the pregnancy and implantation ratio in women with recurrent IVF-ET failures. Eighty-six women received in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) with a record of three or more previous IVF-ET failures. Participants were randomly distributed into two groups. Group A (n=43) received unfractionated heparin 5 000 IU twice daily, and group B (n=43) did not take any antithrombotic drugs. Coagulation abnormalities such as factor V Leiden (FVL) mutation, methylene tetra hydro folate reductase (MTHFR) mutation and prothrombin mutation (FII) were evaluated. Age, body mass index, basal follicular stimulating hormone, basal estradiol, duration of infertility, and number of IVF-ET failures were compared between two groups. Results: 45.0% and 17.4% of women were pregnant with and without MTHFR and prothrombin mutation, respectively, when they received unfractionated heparin treatment. The implantation rate was more in group A (12.5%) than group B (4.3%) and differences in the fertilization rate of the two groups were observed (27.7% vs. 35.9%). The clinical pregnancy rate per cycle was remarkably more in group A (30.2%) than group B (14.0%). Conclusions: Heparin is a safe and valuable treatment for patients with repeated IVF-ET failures. The clinical pregnancy and implantation rates are higher in the heparin-treated group in contrast with the control group. Trial registration: The trial registration was done with clinical registration number of “ IRCT138807202575N1”.

Abstract Background: Premature ovarian failure (POF), is menopause occurring before the age of 40, affecting 1-3% of women worldwide. The risk of POF increases with altered immunological parameters such as FAS and FASL genes, which play a fundamental role in embryogenesis and cellular homeostasis. Objective: The study aimed to investigate the potential role of FAS and FASL genes in POF pathogenesis. Materials and Methods: In this case-control study, the polymorphisms of FAS-670A/G and FASLIVS2nt_124A/G apoptotic genes were analyzed in 51 Iranian women suffering from POF, and 61 healthy controls. Isolation of DNA was done using the salting-out method, and genotypic analysis was performed for all the subjects using the polymerase chain reaction-restriction fragment length polymorphism method. Results: Our results revealed that homozygous FAS-670A/A and G/G, and heterozygous FAS-670A/G are not significantly different between cases and controls (p = 0.99). Also, in different genotyping models of FASIVS2nt_124, polymorphisms were not related to POF risk (p = 0.23). Conclusion: There is no statistical association between these polymorphisms and POF risk in women referred to genetic counseling clinics.

Abstract Background: Primary ovarian insufficiency (POI) is a rare disease clinically characterized by ovarian follicles depletion or dysfunction and menopause before the age of 40 yr as the cut-off age for POI. It is a complex disease, and its etiology involves several factors. However, genetic factors have a predominant role in the susceptibility to the disease. Objective: This study aims to investigate the polymorphisms of rs243865 in the matrix metallopeptidase 2 (MMP2) gene and rs2234693 and rs9340799 in the estrogen receptor 1 (ESR1) gene with susceptibility to POI in Iranian women under 35 yr. Materials and Methods: This case-control study was performed on 150 women with POI and 150 healthy women who were referred to Yazd Reproductive Sciences Institute, Yazd, Iran between May-October 2020. The genotyping of ESR1 rs9340799, rs2234693, and MMP2 rs243865 polymorphism was done using tetra-amplification refractory mutation system-polymerase chain reaction. In addition, haplotype analysis and linkage disequilibrium were investigated by SNPanalyzer software. Results: Our study revealed the frequency of rs243865 TT, CC genotypes in the MMP2 gene and rs2234693 CC, TT; and rs9340799 GG, AA in the ESR1 gene were more prevalent in the case group compared to the control group. In addition, ESR1 rs2234693 and rs9340799 genotypes showed significant association with the development of the disease in our population. Among 4 haplotypes for 2 polymorphisms in the ESR1 gene, rs2234693T/rs9340799A haplotype was associated with conferring risk to POI. Conclusion: ESR1 rs2234693 and rs9340799 polymorphism were strongly associated with our population's POI.

Abstract Ultra‐rare biallelic pathogenic variants in geranylgeranyl diphosphate synthase 1 (GGPS1) have recently been associated with muscular dystrophy/hearing loss/ovarian insufficiency syndrome. Here, we describe 11 affected individuals from four unpublished families with ultra‐rare missense variants in GGPS1 and provide follow‐up details from a previously reported family. Our cohort replicated most of the previously described clinical features of GGPS1 deficiency; however, hearing loss was present in only 46% of the individuals. This report consolidates the disease‐causing role of biallelic variants in GGPS1 and demonstrates that hearing loss and ovarian insufficiency might be a variable feature of the GGPS1‐associated muscular dystrophy.

Qaboosnameh is an educational and ethical book written by Onsor Al-Maali Kikavous, one of Alziar's rulers, in the fifth century for his son Gilanshah. This book has many literary and social values, so that it is considered a collection of pre-Mongol Iranian civilization. The author has used historical and social anecdotes and stories to influence and emphasize his words throughout the book. These stories are told to explain ethical points, and a special context of storytelling can be observed in them. One of the fictional elements that is clearly prominent in Qaboosnameh anecdotes is the narrative element. This research has analyzed the descriptive-analytical form by randomly selecting fifteen anecdotes from Qaboosnameh, the structure of the narrative in this work according to the beginning of the story, story triangle, denouement and complication, etc. In addition to the structure of the plot and how it is formed and its process in the story, two main and effective elements in the narrative such as characterization and perspective have also been explored. According to the results of this research, Onsor Al-Maali has benefited from new storytelling methods in Qaboosnameh anecdotes in addition to expressing moral points consciously and unconsciously. This factor has increased the impact and intimacy of its stories. Onsor Al-Maali has also made innovations in terms of perspective and has expressed a new perspective by combining several perspectives. In his view, although he is aware of all the events, he refrains from narrating all the events, excessive bias and details, and leaves the decision to the reader.

Doxorubicin (DOX) is an effective anticancer drug used for the treatment of osteosarcoma. Liposomal nanocarriers for doxorubicin administration are now regarded as one of the most promising approaches to overcome multiple drug resistance and adverse side effects. The use of hydrogel as a 3D scaffold to mimic the cellular environment and provide comparable biological conditions for deeper investigations of cellular processes has attracted considerable attention. This study aimed to evaluate the impact of liposomal doxorubicin on the osteosarcoma cell line in the presence of alginate hydrogel as a three-dimensional scaffold. Different liposomal formulations based on cholesterol, phospholipids, and surfactants containing doxorubicin were developed using the thin-layer hydration approach to improve therapeutic efficacy. The final selected formulation was superficially modified using DSPE-mPEG2000. A three-dimensional hydrogel culture model with appropriate structure and porosity was synthesized using sodium alginate and calcium chloride as crosslinks for hydrogel. Then, the physical properties of liposomal formulations, such as mechanical and porosity, were characterized. The toxicity of the synthesized hydrogel was also assessed. Afterward, the cytotoxicity of nanoliposomes was analyzed on the Saos-2 and HFF cell lines in the presence of a three-dimensional alginate scaffold using the MTT assay. The results indicated that the encapsulation efficiency, the amount of doxorubicin released within 8 h, the mean size of vesicles, and the surface charge were 82.2%, 33.0%, 86.8 nm, and −4.2 mv, respectively. As a result, the hydrogel scaffolds showed sufficient mechanical resistance and suitable porosity. The MTT assay demonstrated that the synthesized scaffold had no cytotoxicity against cells, while nanoliposomal DOX exhibited marked toxicity against the Saos-2 cell line in the 3D culture medium of alginate hydrogel compared to the free drug in the 2D culture medium. Our research showed that the 3D culture model physically resembles the cellular matrix, and nanoliposomal DOX with proper size could easily penetrate into cells and cause higher cytotoxicity compared to the 2D cell culture.

Abstract Recurrent pregnancy loss is a distinct disorder defined as the loss of at least 2 pregnancies before the 20 th wk of gestation. With half of the genome of the embryo belonging to the father, the integrity of the sperm genome is crucial for a successful pregnancy. Semen analysis is recommended for men in such cases to evaluate sperm concentration, morphology, vitality and motility. However, other important sperm parameters such as sperm epigenetics, aneuploidy, Y chromosome microdeletion and chromatin integrity also correlate with successful pregnancy and delivery rate. This article examines the use of different sperm tests and their importance in male partners of women suffering from recurrent pregnancy loss.

Abstract Background Intellectual disability is characterized by impairments in adaptive behavior and cognitive functioning manifested during the developmental period. Since disabilities are heterogeneous, variant analysis can help us confirm and accurately diagnose children with intellectual disabilities. Some papers reported that bi-allelic variants of the NSUN2 gene caused a group of neurological disorders, including non-syndromic autosomal recessive intellectual disability (NS-ARID), Dubowitz syndrome, and familial restrictive cardiomyopathy 1 (RCM1). We report on a consanguineous family with three siblings diagnosed with intellectual disability. Case presentation The 7-year-old female was referred to Ali-Asghar hospital, Zahedan, Iran, with clinical manifestations comprising moderate intellectual disability, ptosis, long face, and short stature. Chromosome banding, metabolic testing, and magnetic resonance imaging examinations revealed no abnormalities. Accordingly, other affected siblings born of the same parents were considered. Whole-exome sequencing (WES) was conducted on the sufferer to consider NS-ARID variants. Findings identified a variant with uncertain significance (NM_017755.6: c.593 T > G) in the NSUN2 gene in the proband. This variant was confirmed through Sanger sequencing of the affected and unaffected family members. Besides, the computational results showed that the L198R exchange could change the interaction between wild-type and other residues in the protein. The affected patients with NS-ARID had similar clinical characteristics and genetic abnormalities. Conclusion Taken together, we described the variant in three Iranian siblings; further expanding of the other variants involved in the disease will be evident by using high-throughput sequencing technologies.

Abstract Background: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder, which affects about 15-20% of women of reproductive age. The most important etiopathogenesis factor in its incidence is hyperandrogenism; over 70 candidate genes are known to be associated with this syndrome, such as the androgen receptor (AR) gene which encodes a steroid receptor and is located on the Xq11-12 chromosome. The N-terminus of exon 1 of AR contains a polymorphic trinucleotide repeat (CAG)n region that encodes glutamine tract. There are some studies showing that shorter AR CAG repeats are significantly related to enhanced AR sensitivity. Objective: This study investigated the frequency of the polymorphic expansion of the trinucleotide CAG repeats of AR in PCOS. Materials and Methods: 160 Iranian women aged 17-40 yr participated in this case-control study: 80 women as PCOS patients and 80 women as healthy controls according to the Rotterdam criteria. Other similar phenotype factors such as hyperandrogenism were not considered as PCOS. The frequency of polymorphic expansion of CAG trinucleotide repeats in PCOS patients was compared with the frequency in non-PCOS controls in using two primer sets for nested polymerase chain reaction. The polymerase chain reaction products were visualized on polyacrylamide gel and then were confirmed by a sequencing process. Results: The results did not show a significant correlation between the frequency of CAG repeats in AR and PCOS incidence. Conclusion: In contrast to some previous reports, the present data showed that the CAG length in PCOS cases did not significantly differ from that of controls. So, the AR (CAG)n does not appear to be a major factor for PCOS in Iranian women.

Abstract Background: Lymphoid-tyrosine-phosphatase which is encoded by the protein tyrosine phosphatase non-receptor 22 (PTPN22) gene plays a pivotal role in the regulation of immune responses by dephosphorylating several signaling intermediates of immune cells. Objective: Since a balanced immune response has been shown to be important during pregnancy, the purpose of this research was to compare the frequency of the PTPN22 C1858T polymorphism in women with unexplained recurrent pregnancy loss (URPL) vs. in a control group for the first time. Materials and Methods: Genomic DNA from 200 individuals with URPL and 200 individuals without URPL (the control group) at the infertility center in Yazd, Iran was isolated using the salting-out method. The PTPN22 C1858T polymorphism of the two groups was analyzed using polymerase chain reaction-restriction fragment length polymorphism. Genotype frequencies in the women with URPL and the fertile control group were compared using the Chi-square test. Results: There were significant differences in the frequency of the PTPN22 1858T polymorphism in the URPL individuals vs. the healthy controls, i.e. 32.0% and 21.5%, respectively (p = 0.01). Conclusion: Our findings suggest that the PTPN22 1858T polymorphism could play a role in recurrent pregnancy loss. Therefore, genotyping of the mentioned polymorphism can help clinicians to predict the probable risk of URPL.

Abstract Background: Androgens play a role in the development of male phenotype and spermatogenesis during puberty, the function of which is regulated by the androgen receptor (AR) gene. There is a polymorphism site in exon 1 of the gene encoding this receptor that can have different frequencies of CAG trinucleotide repeats and leads to the formation of polyglutamine chains of different lengths in the N-terminal domain of the AR protein and reduced sperm production by affecting spermatogenesis. Objective: To investigate whether the cause of a group of unexplained infertilities could be the increased frequency of CAG repeats in the AR gene of patients with oligozoospermia and azoospermia. Materials and Methods: In this case-control study, 84 men including 42 with unexplained infertility As a case group and 42 fertile men as a control group were selected. The frequency of CAG repeats was determined by the polymerase chain reaction method and then the difference in the frequency of these repeats was determined based on the difference in band size on the agarose gel. Results: The mean CAG repeat length in the azoospermia and oligozoospermia group was 17.5 ± 0.63 and in the fertile group it was 16.11 ± 0.75 (p = 0.46). In addition, most men (88.1% in the case group and 71.41% in the control group) had 13-23 repeats. Conclusion: No significant correlation was found between CAG repeat length and the risk of male factor infertility in an ethnically defined population of Iranian men. The role of regulatory factors and epigenetic changes should be taken into account too.

Abstract Background: Recurrent pregnancy loss (RPL) is the most common complaint of pregnancy in females with a prevalence of 5%. Numerous documents have shown that single nucleotide polymorphisms are able to change miRNA transcription and/or maturation, which may alter the incidence of disorders such as RPL. Objective: To assess the relationship of miR-146aC > G (rs2910164) and miR-196a2T > C (rs11614913) with RPL susceptibility in Iranian women. Materials and Methods: Blood samples were collected from 214 women who had experienced at least two consecutive spontaneous miscarriages (case) and 147 normal individuals without a history of miscarriage (control). MiR-146aC > G and miR-196a2T > C genotypes were evaluated via the restriction fragment length polymorphism technique. Results: The genotypes incidence did not show a significant difference in pre-miR-146aC > G polymorphism CC vs CG + GG (p = 0.854; OR = 0.933; 95% CI) and CC + CG vs GG (p = 0.282; OR = 1.454; 95% CI). Also, no significant difference was observed between pre-miR-196a2T > C polymorphism TT vs TC + CC (p = 0.862; OR = 0.938; 95% CI) and TT + TC vs CC and (p = 0.291; OR = 1.462; 95% CI) in both the case and control groups. Conclusion: The results showed that although the distribution of miR-146aC > G and miR-196a2T > C was different between the unknown RPL and control groups, these variances were not statistically significant.

Abstract Background: Recurrent pregnancy loss (RPL) refers to the incidence of two or more abortions before the first half of pregnancy. Oxidative stress has been hypothesized to play a central role in RPL. Objective: To investigate the relationship between Q192R and L55M polymorphisms of PON1 as antioxidant enzyme and the risk of RPL. Materials and Methods: In this case–control study, 110 women with RPL (case) and 110 healthy fertile women (control) referred to the Research and Clinical Center for Infertility, Shiraz, Iran were enrolled. Genomic DNA was extracted from the peripheral blood in all participants. Polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism method. Results: Statistical analysis of Q192R polymorphism showed a significant difference for the RR genotype between the case and control group (OR = 11, CI = 1.39–86.87, p = 0.005) but none for the QR and QQ genotypes. No significant association was observed between the R and Q allelic frequency in the RPL participants compared to the control group (p = 0.53). Also, statistical analysis of the L55M polymorphism for MM genotype in the case group compared with the control group showed a significant difference (OR = 3.59, CI = 0.97–13.30, p = 0.042), but none for the LM and LL genotypes. Conclusion: The findings showed a significant correlation between the Q192R polymorphisms and the L55M PON1 enzyme and RPL in this study population.

Objective: To investigate the frequency of -786T>C variant in endothelial nitric oxide synthase (eNOS) gene promoter in Iranian women with recurrent pregnancy loss. Methods: Blood samples were obtained from 100 unrelated women affected by recurrent pregnancy loss and 100 unaffected women as the controls. Genomic DNA was extracted and -786T>C polymorphism in eNOS gene promoter was investigated by PCR-RFLP method. Statistical analyses and Hardy-Weinberg equilibrium in the groups of patients and controls were performed by Chi-square test and SPSS standard software (Version 21). Results: The frequency of homozygous TT was 40% in cases and 46% in the control group; the frequency of CC was 7% in cases and 5% in the control group; frequency heterozygote TC was 53% in cases and 49% in the control group. Genotype frequencies between the two groups showed no significant differences (P>0.05). Conclusions: The -786T>C polymorphism is not more frequent in recurrent pregnancy loss in this population.

Background: Infertility is a common problem in testicular cancer. Affected men often decide to undergo sperm banking before chemo/radiotherapy. The cumulative effects of therapy can considerably reduce fertility. Objective: Testicular cancers impair fertilizing ability, even before diagnosis. This study tries to verify individual traits and semen quality in patients with testicular cancer. Materials and Methods: This observational study analyzed 190 semen of patients with testicular cancer (16 to 47 yr old) referred to the sub-fertility laboratory at the St. Mary hospital for semen banking prior to treatment carcinoma. Several aspects of their semen analyses were examined. The cases were divided into four different categories: seminoma, teratoma, mixed germ cell tumors and others. Results: The results showed that 23 cases were azoospermic, and 13 of the patients who were not azoospermic, their sperm of “normal” morphology were too few to count. Among patients that could produce spermatozoa, 59.4% had a sperm concentration of < 20 × 10 6 /ml. The mean of “motility excellent” and “sluggish” taken together in all the cases was 47.2%. More than 92% of the patients had an abnormal morphology. The morphology of sperm is the most sensitive semen parameter that is affected by testicular carcinoma. Conclusion: Abnormal spermatogenesis is seen in most patients with testicular cancer before treatment with radiation, chemotherapy, or surgery. The causes of poor semen quality in cancer patients are not well-understood, but the patients with impaired spermatogenesis should have precise examination to find out the correct diagnosis of problem and preserve the fertility before any treatment.

Background: Genetic factors could account for recurrent pregnancy loss (RPL). The RAN gene is a member of the "large RAS family" and a small GTPase that is essential for the translocation of Ribonucleic acid (RNA) and proteins through the nuclear pore. Mutation in the RAN constitutive gene could stop DNA synthesis and alter the expression of genes in the uterus, likely playing a role in recurrent miscarriage. Objective: The aim was to investigate the frequency of RAN (rs 14035) polymorphism in women with RPL compared with women without abortion history. Materials and Methods: In this case-control study, 100 women with at least two consecutive miscarriages before the 20th wk of gestation and having spouses with karyotype and normal sperm parameters as the case group and 100 women with no history of abortion and having at least one successful pregnancy and normal delivery as the control group. The groups were age matched (20-40 yr). The rs 14035 polymorphism of RAN gene was investigated by Polymerase Chain Reaction-Restriction Fragment Length poly morphism technique and the frequency of which was compared between the two groups. Results: The frequency of TT, TC, and CC genotypes of RAN gene polymorphism in the case group were 9%, 40%, and 51%, respectively, and in the control group were 11%, 38%, and 51%, respectively. There was no significant difference in the genotypes between two groups (p = 0.882). Conclusion: According to our results, it seems that RAN polymorphism (rs 14035) is not associated with the risk of RPL in this study population.

Background: Using blood-based biomarkers such as microRNAs (miRNAs) may allow particularly effective and minimally invasive diagnosis and treatment of endometriosis. Objective: We evaluated the differential expression of circulating miRNA-185-5p (miR-185-5p), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) target genes between endometriosis and healthy women. Materials and Methods: 25 women with a history of endometriosis (grad III-IV) diagnosed by laparoscopy as the case group and 25 women without endometriosis underwent laparoscopy for ovarian cysts or pelvic pain as the control group were enrolled in this case-control study. Blood samples were obtained, and total RNA was used for high-throughput small RNA sequencing, and this was confirmed by means of quantitative real-time polymerase chain reaction (qRT-PCR). Results: miRNA expression profiling using non-coding RNA sequencing revealed that one miRNA including miR-185-5p was significantly down-regulated in the case group compared with the controls. The qRT-PCR results showed significant downregulation of the expression level of miR-185-5p (p < 0.01) in the plasma of the case group. Receiver operating characteristic (ROC) curve analysis showed the area of miR-185-5p under the ROC curve for endometriosis diagnosis was 0.919 (p < 0.001). The RT-PCR results demonstrated that there was no significant difference in the expression of VEGF and PDGF mRNA of blood samples in the cases compared to the control group (PDGF, p = 0.09 and VEGF, p = 0.36). Conclusion: The low expression of miR-185-5p in the plasma of women with endometriosis could be employed as an important non-invasive biomarker for early detection and screening of endometriosis by blood samples.

Background: Vascular endothelial growth factor A (VEGFA) plays a key role in angiogenesis during human placenta formation and its abnormal expressions have been reported in placental tissues of women with recurrent miscarriage (RM). Objective: The aim of this study was to evaluate the correlation of polymorphism of VEGF1154 G/A gene in RM and In Vitro Fertilization (IVF) failures. Methods: The peripheral blood samples of women with RM, IVF failures and healthy women with live born children, as control group were collected. DNA samples were isolated and VEGF 1154G/A polymorphism was evaluated by polymerase chain reaction and restriction fragment length polymorphism. Single nucleotide polymorphism scanning was done using MnII restriction enzymes for 1154 G/A. Results: The findings of this study showed that the VEGF 1154 A/A and VEGF 1154 G/A mutation frequencies in both RM and IVF failure groups were significantly higher than those in the control group (p=0.005). The homozygous AA mutant genotype frequency in the control group was 0, While in the RM and IVF failure groups it was 30% and 13.9%, respectively (p=0.005). Moreover, the heterozygous AG genotype frequencies were higher in the RM (66.7%) and IVF failure (77.8%) compared to those in the control group (58.3%). Conclusions: It was concluded that VEGF 1154 A/A and VEGF 1154 G/A polymorphisms were associated with both RM and IVF failures. However, their relation with IVF failures was more common than RM in A/G genotype, while in A/A, the RM was higher than IVF failure.

Abstract Background Tudor domain-containing proteins (TDRDs) play a critical role in piRNA biogenesis and germ cell development. piRNAs, small regulatory RNAs, act by silencing of transposons during germline development and it has recently been shown in animal model studies that defects in TDRD genes can lead to sterility in males. Methods Here we evaluate gene and protein expression levels of four key TDRDs (TDRD1, TDRD5, TDRD9 and TDRD12) in testicular biopsy samples obtained from men with obstructive azoospermia (OA, n = 29), as controls, and various types of non-obstructive azoospermia containing hypospermatogenesis (HP, 28), maturation arrest (MA, n = 30), and Sertoli cell-only syndrome (SCOS, n = 32) as cases. One-way ANOVA test followed by Dunnett’s multiple comparison post-test was used to determine inter-group differences in TDRD gene expression among cases and controls. Results The results showed very low expression of TDRD genes in SCOS specimens. Also, the expression of TDRD1 and TDRD9 genes were lower in MA samples compared to OA samples. The expression of TDRD5 significantly reduced in SCOS, MA and HP specimens than the OA specimens. Indeed, TDRD12 exhibited a very low expression in HP specimens in comparison to OA specimens. All these results were confirmed by Western blot technique. Conclusion TDRDs could be very important in male infertility, which should be express in certain stages of spermatogenesis.

Abstract Background Congenital adrenal hyperplasia is a rare autosomal recessive disorder where the mutation in P450 family 17 subfamily A member 1 gene (CYP17A1) is involved in its etiology. The disorder represents itself with low blood levels of estrogens, androgens, and cortisol that generally couples with hypertension, Hypokalemia, sexual primary amenorrhea, infantilism and in affected individuals. Case In this study, the CYP17A1 gene in a 14-year-old female was examined. The karyotype of the patient was 46, XX, and the analysis of the CYP17A1 gene by Sanger sequencing revealed a novel homozygous deletion c.1052-1054CCT which led to isolated 17,20-lyase deficiency. Conclusion In conclusion, this study report an in-frame deletion which results in isolated 17, 20-lyase deficiency, and the mutation might be used for diagnosis in other patients with distinctive clinical symptoms

Backgrounds and Aim: One of the effective strategies for targeting chemotherapy in the treatment of cancer is the use of lipid nano-carriers. In this study, an optimal formulation of niosomal drug containing doxorubicin has been developed to better fight cancer cells. Material and Methods: Niosomal vesicles were prepared using phosphatidylcholine (22%), span60 (52/5%), cholesterol (22/5%) and DSPE-PEG2000 (5%) by thin-film method. Doxorubicin were loaded into the niosomes using inactive loading method. Their physico-chemical features were assayed using Zeta-Sizer, FTIR and SEM, and drug release amount was calculated at 37° C and 44° C. At the end, the toxicity of the nano drug carrier system was measured on the KG-1 cell line of the bone marrow cancer by MTT method. Results: Niosomal vesicles containing Doxorubicin showed the size of 160.37±65.2 nm, 94.18% drug encapsulation efficiency -58.11± 1.24 mV of zeta potential and polydispersity index (PDI) of 0.234±0.02 The prepared niosomal system presented drug controlled release and FTIR investigation showed almost no interaction between nano-carrier containing drug and the drug itself. As well, morphological examination of nano-carriers using SEM microscopy revealed that they have spherical structures. Also, cellular studies showed that drug toxicity was higher in encapsulated conditions compared to non-encapsulated conditions. Conclusion:The results of this study, meanwhile confirming the proper physicochemical characteristics of the system and being Slow-release system indicate that this nano-carrier anionic increases the toxicity of the drug for the KG-1 cell line of the bone marrow, thus, this niosomal nano-carrier can be a suitable carrier for drug delivery to cancer cells.

Background: The quality of oocyte is often considered as a limiting factor for fertility, especially IVF. Some mitochondrial mutations, particularly the 4977-bp deletion increase with the age. Thus, this mutation can serve as a marker for cell aging, which indicates the reduced quality of the oocytes for fertilization. It has been suggested that this can also be investigated in the blood cells of women with IVF failure. Objective: 1-Determination of the frequency of 4977-bp deletion in women with IVF failure, 2-Investigation of the relationship between 4977-bp deletion and the age of patients. Materials and Methods: Polymerase chain reaction was used to detect the 4977-bp deletion in blood samples of 52 IVF failure women and 52 women who had at least one healthy child. After polymerase chain reaction with deleted and wild-type primers, the products were examined using agarose gel electrophoresis. Results: 48.07% of women with IVF failure and 34.62% of healthy women had a mitochondrial 4977-bp deletion, with p=0.163 and OR: 1.749. Also, in association with the age of these patients and the frequency of 4977-bp mutation, p and OR were obtained 0.163 and 1.749, respectively and frequency of this mutation was higher in patients over 35 yr old compared to other subgroups (Patients ≥35: 57.69). Conclusion: According to the findings of this study, there is no a significant relationship between the frequency of mitochondrial 4977-bp mutation and failure in IVF.

Background: Tumor necrosis factor-alpha (TNF-α) is a multifunctional cytokine that regulates different cellular activities related to spermatogenesis. Tumor necrosis factor-alpha receptor 1 (TNFR1) mediates TNF-α activity and polymorphism in TNFR1 could lead to gene dysfunction and male infertility. Objective: The aim of this study is to determine the association of TNFR1 36 A/G polymorphism with the idiopathic azoospermia in Iranian population. Materials and Methods: This case-control study included 108 azoospermic and 119 fertile men. This research investigated the frequency of TNFR1 36 A/G polymorphism in cases who were idiopathic azoospermic men referred to Yazd Research and Clinical Center for Infertility, Iran in comparison with controls. polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method was used to investigate the polymorphism in both case and control groups. PCR fragments were digested by Mspa1I enzyme and products were appeared by gel electrophoresis. The abundance of A→G was calculated in the azoospermic and healthy men. Results: According to the present study, GG and AG genotypes frequency in the azoospermic men group were higher than the control group (OR= 2.298 (1.248-4.229), p=0.007), (OR=1.47 (0.869-2.498, p=0.149). Our findings also showed that G allele frequency in azoospermic men had significant difference compared to the control group (OR=2.302 (1.580-3.355), p

Background: Ovarian hyperstimulation syndrome (OHSS) is one of the most important complications of assisted reproduction treatment. Many substances are involved in the regulation of the vascular permeability, which have been concerned to cause OHSS. Vascular endothelial growth factor (VEGF) has emerged as one of the main angiogenic factors, which could be responsible for increased vascular permeability. Objective: In this study the association of vascular endothelial growth factor - 460C/T and +405 G/C polymorphisms and susceptibility to ovarian hyperstimulation syndrome was evaluated. Materials and Methods: In this cross sectional study, VEGF gene polymorphisms were amplified by Polymerase chain reaction- Restriction Fragment Length Polymorphism in 75 women with established OHSS (case group) and 85 normoresponder (control group) which received conventional ovarian stimulation regimen. Results: There was no significant difference in the frequency of -460 C/T polymorphism between cases and controls (p=0.85). The frequency of +405 G/C polymorphism was significantly higher in the OHSS women (p=0.03, OR=2.44; 95% CI=1.23-4.82). Conclusion: In women who developed OHSS, VEGF gene polymorphism +405 could be effective. Two of the polymorphisms -460 C/T and +405 G/C were reported to be associated with increased VEGF basal promoter activity. However, only +405 G/C gene polymorphisms were more frequent in cases than controls

Background and Objectives: Adolescence is one of the important period in growth and evolution process, Also, eating disorders in adolescences, especially girls is one of the major problems in communities. Therefore, an effective education is of special priority for prevention of eating disorders. The current study was performed with the goal of assessment of the effect of nutrition education on eating disorders attitude in girls high school students. Methods: This non-experimental study with a single group pre- and post-test design, was performed using purposive sampling method on 97 students of the first year of high school, in 2015. Data collection tool was EAT-26 standardized questionnaire, which was completed by the participants using self-report method before and 3 months after the education. Data were analyzed using paired t-test. The significance level was set at p

Background: Human leukocyte antigen-E (HLA-E)is a non-classical major histocompatibility complex (MHC) class I antigens which expressed on extra villous cytotrophoblast, which interacts with NKG2A, is an inhibitory receptor on natural killer (NK) cells and leading to down regulation of immune response in the maternal-fetal interface and provides maternal immune tolerance of the fetus. Objective: This study was designated to investigate the gene frequencies of E0101 and E0103 in HLA-E gene in Iranian women with recurrent spontaneous abortion (RSA). Materials and Methods: Amplification Refractory Mutation System (ARMS-PCR) technique was carried out to detect polymorphism in exon 3 of the HLA-E gene in women with RSA and controls (n=200). Differences between groups were analyzed by SPSS19 software using χ2 test. Results: There was no significant difference in the allele frequencies of the HLA-E polymorphism between RSA and fertile controls but HLA-E 0101/0103 heterozygous genotype was found to be significantly higher in RSA group (p=0.006, OR=1.73), so this genotype might confer susceptibility to RSA. Conclusion: Our results suggest that HLA-E 0101/0103 heterozygous genotype leads to increase of RSA risk. It seems that by genotyping of HLA-E polymorphism, we can predict the risk of RSA in infertile women

Background: Breast cancer is the most common type of cancer among women, and is among the five most prevalent cancer types among Iranian women. Advanced-stage breast cancer is often correlated with distant metastases. Alterations in gene expression affect general cytoskeleton changes during differentiation and oncogenesis, and can be considered an important factor in tumor progression. Gelsolin plays a significant role in actin assembly and has been introduced as a tumor activator. The aim of this study was to evaluate the expression of Gelsolin in breast cancer as well as its correlation with patients’ clinical parameters. Methods: In this study, 70 breast cancer patients, who had been referred to Imam Khomeini Complex Cancer Institute for surgery were randomly selected. Normal and tumor tissues were prepared and stored at -80°C. Gelsolin gene expression was measured using real-time polymerase chain reaction (PCR). Results: The results showed that Gelsolin gene expression had increased in 68.6% of the tumor samples. In addition, there was a significant association between increased levels of gene expression and tumor progression stages (P < 0.05). However, there was no significant association between increased levels of gene expression and other clinical findings, such as tumor grade, tumor size or patient age. Conclusion: The results revealed that Gelsolin gene expression had increased in the tumor samples. Gelsolin overexpression also resulted in increased lymph node involvement in breast cancer. The expression of this gene also increased significantly during advanced stages of breast cancer; however, there was no significant relation between Gelsolin expression and tumor grade or tumor size.

Preeclampsia is an important pregnancy disorder with serious maternal and fetal complications which its etiology has not been completely understood yet. Early diagnosis and management of disease could reduce its potential side effects. The vascular endothelial growth factor (VEGF) family including VEGF-A is the most potent endothelial growth factor which induces angiogenesis and endothelial cell proliferation and has basic role in vasculogenesis. VEGF and its tyrosine kinase receptors (Flt1 and KDR) are major factors for fetal and placental angiogenic development. Finding mechanisms involved in expression of angiogenic factors may lead to new prognostic and therapeutic points in management of preeclampsia. Recent researches, has shown capability of some anti-angiogenic factors as potential candidate to be used as early predictors for preeclampsia. Soluble fms-like tyrosin kinase-1 (sFlt1) is a truncated splice variant of the membrane-bound VEGF receptor Flt1, that is produced by the placenta and it can bind to angiogenic growth factors and neutraliz, their effects. It is also observed that the ratio of sFlt1 to placental growth factor is valuable as prognostic marker. In this review, VEGF family member’s role in angiogenesis is evaluated as biomarkers to be used for prediction of preeclampsia.

Background: Recurrent pregnancy loss (RPL) has been defined as two or more miscarriages before 20th week of gestation. It seems that IL-27 may reduce inflammatory responses and affect the survival of the embryo during human pregnancy. IL-27 polymorphisms may influence RPL by altering the levels or the activity of gene product. Objective: We studied for the first time the association of IL-27 -964 A>G single nucleotide polymorphism (SNP) with RPL in Iranian women. Materials and Methods: A case-controlled study was performed on two groups consisting of 150 healthy women with at least one delivery (control group) and 150 women with two or more primary RPLs history (RPL group). The -964 A>G SNP in IL-27 gene was determined by PCR-RFLP technique. Genotype and allele frequencies were compared using 2 tests between two groups. Results: There was no difference between the two groups regarding age of women (29±4.4 [control] vs. 30.84±5.2 years [case]). In the RPL group, the genotype frequencies of -964 A>G polymorphism were AG (49.3%), AA (40%), and GG (10.7%), and in the control group, they were AG (43.3%), AA (48.7%), and GG (8%). There was no significant difference between the genotypes of AA, AG, and GG in two groups (p=0.23). As the frequency of allele A was 64.7% in the RPL group and 70.3% in the control group, the difference in frequency of allele A in -964 A>G between two groups was not significant (p=0.19). Conclusion: Our findings indicate that SNP of -964 A>G in IL-27 gene is not a risk factor for RPL in Iranian women.

Background: Infertility is accompanied by numerous psychological and social problems. Infertile couples are more anxious and emotionally distressed than other fertile people. Previous studies suggested that infertility is more stressful for women than men. Objective: The purpose of this study was to determine the status of general health of infertile couples. Materials and Methods: This cross-sectional study evaluated general health of 150 infertile couples attending to Yazd Research and Clinical Center for Infertility that were selected consequently. The data were gathered by the researchers, based on face to face interview before and after three months of treatment by two questionnaires. The first questionnaire had questions on demographic information and the second one was the General Health Questionnaire-28 (GHQ-28). This questionnaire has four sub- scales areas. All data were transferred directly to SPSS 15 and analyzed. Results: The mean age of women was 28.3 and men were 32.4 years. The scores for all sub- scales of GHQ in women were more than men. There was significant difference between age and general health at physical symptoms scales (p=0.002), anxiety and sleep disorders (p=0.003). The age group 25-29 years had higher scores (more than 7) than other age groups. There was significant difference between the scale of social dysfunction and results of treatment. Conclusion: Our results, similar to the previous studies have revealed negetive social and mental effects of infertility on women is more than men, so there is need that they be educated specially.

"nAim of this study is to determine the risk of adverse pregnancy outcome by maternal serum alpha-fetoprotein (MSAFP) level. We followed 295 pregnant women from MSAFP screening in the 14th to 22th week of gestation until the end of pregnancy and information on pregnancy outcome have been recorded in questionnaires. Of 295 pregnant women, 270 had term labor and 25 had preterm labor. The frequencies of pregnancy outcomes were as following: 3 (1.01%) stillbirths, 25(8.47%) preterm labor, and 10 (3.4%) preterm rupture of membranous (PROM), 15 (5.1%) pre-eclampsia, 23 (7.8%) oligohydramnious, and 1 (0.33%) miscarriage. The mean of preterm labor was significantly associated with the higher level of MSAFP (P =0.021). The mean was 55.1 ng/cc in preterm labor and 41.1 ng/cc in term labor. Also, second trimester MSAFP levels were higher in women with pre-eclampsia (P

BackgroundThe aim of this study was to assess plasma levels of endothelium- and heart-associated microRNAs (miRNAs) miR-126 and miR-499, respectively, using quantitative reverse transcriptase polymerase chain reaction.MethodsA two-step analysis was conducted on 75 patients undergoing off-pomp coronary artery bypass graft (CABG) surgery. Five biomarkers of inflammation and cardiac injury were assessed in addition to the above-mentioned miRNAs.ResultsPlasma concentrations of miRNAs were found to be significantly correlated with plasma levels of cardiac troponin I (cTnI) (miR-499, r 0.49, p~0.002; miR-126, r = 0.30, p~0.001), indicating cardiac damage. Data analysis revealed that miR-499 had higher sensitivity and specificity for cardiac injury than miR-126, which reflects more endothelial activation. Interestingly, a strong correlation was observed between both miRNAs and uric acid (UA) levels with ventricular contractility measured as ejection fraction (EF) (miR-499/EF%, r = 0.58, p~0.004; UA/EF%, r = -0.6, p~0.006; UA/miR-499, r = -0.34; UA/miR-126, r = 0.5, p~0.01).ConclusionsIn patients undergoing CABG, circulating miR-126/499 is associated with presentation of traditional risk factors and reflects post-operative response to injury. Plasma pool of miRNAs likely reflects extracellular miRNAs which are proportional to intracellular miRNA levels. Therefore, circulating levels of these miRNAs have prognostic implications in detection of higher risk of future cardiovascular events.