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The illuminating picture of genetic mechanisms underlying the development of type 2 diabetes (T2DM) includes differently accumulated genetic polymorphisms that increase the risk along with environmental factors. A number of single nucleotide polymorphisms (SNPs) are indicated to be linked with T2DM, but also conflicting results have been found. To examine the contribution of these polymorphisms in conferring susceptibility to T2DM, the association of HHEX rs1111875A/G and CDKN2A/B rs10811661C/T common gene polymorphisms with the risk of T2DM in an Iranian population was evaluated. In this study participated 140 patients and 140 controls. Genomic DNA was extracted from samples and genotyping of the polymorphisms was performed by the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) technique. A significant association was found with the G allele (OR = 1.729, CI = 1.184-2.523, P = 0.004) and GG genotype (OR = 2.921, 95% CI = 1.789-4.771, P< 0.001) of the rs1111875A/G SNP for susceptibility to T2DM in the recessive model. Furthermore, compared with the GG genotype, individuals with the GA genotype had a lower risk to develop T2DM (OR = 0.237, 95% CI = 0.137-0.408, P< 0.001) in the additive model. In addition, an association between the polymorphism and BMI in regard to the risk of T2DM was identified. The genotype and allele frequencies of the rs10811661C/T polymorphism did not show a statistically significant association with T2DM in any genetic model. Our results show that the rs1111875A/G polymorphism is an important susceptibility polymorphism for the development of T2DM in the Iranian population. Also, these findings support that this polymorphism is a key genetic risk factor for the development of T2DM in multiple ethnic populations. [ABSTRACT FROM AUTHOR]

Purpose: A healthcare unit's effectiveness largely depends on how well its interprofessional teams work together. Unfortunately, the strategies used to improve these teams often lack substance. This study analyzed these strategies and found a performance gap., Design/methodology/approach: This study took a unique mixed-method approach, systematically reviewing both qualitative and quantitative studies that identified strategies to enhance interprofessional teams in healthcare units. To gauge the effectiveness of these strategies, the researcher utilized an Importance-Performance Analysis (IPA) in four specialized clinical training centers in Hamadan province, Iran. The analysis of the IPA involved 35 experts from these centers as the statistical population., Findings: Based on a systematic review, there are seven categories: contextual, strategic, communication, organizational, individual, Human Resources Management (HRM), and environmental for promoting interprofessional teams with a total of 36 sub-indicator. Based on the IPA, the HRM aspect shows the most extensive performance gap. The individual and organizational aspects fall under resource wastage, and the environmental aspect is within the indifferent zone. Also, some critical sub-indicators, such as incentives/rewards, roles and responsibilities, financial resources, team-initiated innovation, the culture of respect, partner resources, humility, data availability, set expectations, and team availability, are in the weak areas., Practical Implications: This research has identified critical areas for improvement in promoting teamwork in clinical training centers through a comprehensive gap analysis. It also presents practical policy solutions to address these weak points, providing a clear roadmap for enhancing interprofessional teams in healthcare units., Originality/value: Improving teamwork in healthcare can be challenging, but it is possible with proper strategies and tools. One of the highlights of the recent study was the combination of systematic review studies with IPA to identify areas for improving interprofessional teamwork in clinical training centers., (© Emerald Publishing Limited.)

Blastocystis is the most common intestinal parasite found in epidemiological studies in Iran. The genus Blastocystis comprises multiple subtypes (ST), evincing the existence of extensive intrageneric diversity. Meanwhile, information on Blastocystis STs in domestic animals in Iran is limited. This study was designed to identify the prevalence and subtype distribution of Blastocystis in domestic animals and to evaluate the extent of zoonotic origin of human Blastocystis carriage. A total of 395 faecal samples from farm animals (220 from poultry, 100 from sheep and 75 from cattle) and 23 Blastocystis positive samples from humans (available from the previous report of this study and included for reference) from the Khuzestan province, southwestern Iran, were analysed. Standard parasitological methods and PCR-based analysis of the SSU-rRNA gene were used. Overall, 115 (29.1%; 95% CI, 26.5%-31.6%) of the animals were positive for Blastocystis sp. by parasitological methods. The highest colonization rate was found in cattle (50.6%, 38/75), followed by sheep (32.0%, 32/100) and poultry (20.4%, 45/220). Eight Blastocystis STs were identified among 55 sequenced isolates from animals (n = 32) and humans (n = 23): ST3 (27.3%), ST14 (25.4%), ST1 (12.7%), ST7 (12.7%), ST2 (9.1%), ST6 (7.3%), ST5 (3.6%) and ST10 (1.8%). Blastocystis ST1 and ST3 were found in both human and non-human hosts, and examples of shared alleles (strains) were observed. Meanwhile, ST2 was observed only in humans, ST5 only in sheep, ST6 only in poultry and ST10 in only cattle. This is the most comprehensive report of Blastocystis STs in farm animals in Iran., (© 2021 Wiley-VCH GmbH.)

Background: Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are multisystemic autoimmune diseases with multifactorial nature. Considering the limitations of the current conventional serological tests for the diagnosis of these diseases, researchers strive to find more new valid biomarkers., Methods: Sixty-nine patients with SLE, 63 patients with RA, and 71 healthy controls were recruited to evaluate the methylation level of interferon-induced protein 44-like (IFI44L) promoter. Quantitative methylation of the promoter region of the IFI44L gene was measured in extracted DNA of peripheral blood mononuclear cells (PBMCs) with methylation-quantification endonuclease-resistant DNA (MethyQESD) method., Results: Our findings unveiled a drastic hypomethylation of IFI44L promoter in SLE and RA patients compared with healthy volunteers (mean: 40.23% ± 64.54%, 35.19% ± 24.09%, and 71.98% ± 23.83%, respectively; P < 0.001 for both SLE and RA). In comparison between SLE and RA patients with the control group, IFI44L promoter methylation had a sensitivity of 81.15% and 84.12%, respectively, and specificity was 76.05%. The promoter methylation level was not meaningfully different between SLE and RA patients (P = 0.267). Moreover, our analysis revealed that the methylation level of the IFI44L promoter was not significantly different between SLE disease activity and renal involvements (P > 0.05). While RA patients with a higher concentration of CRP had a lower DNA methylation level (P = 0.023)., Conclusion: The methylation level of IFI44L promoter was lower in PBMCs of Iranian patients with SLE and RA than that in the control group. Furthermore, DNA methylation level of the IFI44L promoter had a negative correlation with RA disease activity. However, there was not a significant association with the clinical characteristics of SLE., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: To assess the efficacy of virtual reality (VR)-based vs conventional balance training on the improvement of balance and reduction of falls in people with multiple sclerosis (PwMS)., Design: Single-blinded, randomized, controlled trial., Setting: Musculoskeletal Rehabilitation Research Center, Ahvaz Jundishapur University of Medical Sciences., Participants: PwMS (N=39), randomized into VR (n=19) and control (n=20) groups., Intervention: The VR group performed exergames using Kinect, while the control group accomplished conventional balance exercises. Both groups received 18 training sessions for 6 weeks., Main Outcome Measures: Limits of stability, timed Up and Go (TUG) test, and 10-m walk tests with and without cognitive task and their dual-task costs (DTCs), Berg Balance Scale, Multiple Sclerosis Walking Scale-12, Fall Efficacy Scale-International, Activities-specific Balance Confidence Scale, and fall history were obtained pre- and post intervention and after a 3-month follow-up., Results: At both post intervention and follow-up, TUG cognitive and DTCs on the TUG were significantly lower and the 10-m walk cognitive was significantly higher in the VR group. At follow-up, reaction time and the number of falls demonstrated significant differences favoring the VR group, whereas the directional control revealed significant difference in favor of the control group (P<.05). The other outcomes showed no statistically significant difference at post intervention or follow-up., Conclusions: Both the VR-based and conventional balance exercises improved balance and mobility in PwMS, while each acted better in improving certain aspects. VR-based training was more efficacious in enhancing cognitive-motor function and reducing falls, whereas conventional exercises led to better directional control. Further studies are needed to confirm the effectiveness of recruiting VR-based exercises in clinical settings., (Copyright © 2020 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The optimal dose of anticoagulant warfarin varies among patients to achieve the target international normalised ratio. Although genetic variations related to warfarin pharmacokinetics and vitamin K cycle are important factors associated with warfarin dose requirements, these variations do not completely explain the large interindividual variability observed in the most populations, suggesting that additional factors may contribute to this variability. microRNAs have recently been introduced as regulators of drug function genes, and therefore, may be involved in drug responses. In this study, we aimed to evaluate the possible association between variants in the seed region of microRNAs, which target the genes involved in the action of warfarin and warfarin dose requirement., Methods: 526 samples were collected from Iranian patients. Four selected polymorphisms in the seed region of microRNAs (rs2910164, rs66683138, rs12416605 and rs35770269 in miR-146a, miR-3622a, miR-938 and miR-449c, respectively) were genotyped by PCR-restriction fragment length polymorphism method., Results: rs2910164 C/G in the seed region of miR-146a was associated with warfarin dose requirement (p<0.001); the patients with GG genotype had the higher mean dose of warfarin (40.6 mg/week, compared with 33.9 and 31.8 mg/week for GC and CC genotypes, respectively). The association of other polymorphisms with warfarin dose requirement was not statistically significant., Conclusion: rs2910164 C/G in the seed region of miR-146a is associated with warfarin maintenance dose, likely by disrupting interaction between miR-146a and ATP-binding cassette subfamily B member 1 gene, ABCB1. Therefore, this polymorphism may possibly be a potential factor for assessment of warfarin dose requirements., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease with multifactorial etiology. Several studies show that genetic factors have an important part in the incidence of SLE. The C1QTNF4 gene is involved in the regulation of the inflammatory pathways by pro-inflammatory function. In the present study, we have evaluated the association between C1QTNF4 gene p.His198Gln mutation and risk of SLE., Methods: Forty SLE patients and 40 control subjects were recruited in this case-control study. Genotyping of C1QTNF4 p.His198Gln mutation was performed using real-time polymerase chain reaction high resolution melting method., Results: We found a significant association between this mutation (GG + GC) with the risk of SLE (odds ratio = 6.33, 95% CI = 1.28-31.11). Furthermore, we observed that in the patient group, this mutation leads to early-onset SLE (19.7 ± 4.34 years for mutation carriers compared to 27.7 ± 11.4 years for wild type carriers; P = .003)., Conclusion: Our results suggest that this mutation (p.His198Gln) potentially has an important role in SLE risk in the Iranian population., (© 2020 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: The discriminative validity of fall efficacy scale international (FES-I) in differentiating between fallers and non-fallers, levels of functional mobility, dynamic balance and disability has not been assessed in Persian speaking people with multiple sclerosis (MS)., Objective: To assess reliability, factor structure, construct and known group validity, sensitivity and specificity of FES-I for differentiating individuals with and without a history of fall and determining a cutoff point of the Persian version of the FES-I in people with MS., Method: One hundred thirty people with all subtypes of MS were included. The ability of FES-I in differentiating fall history was assessed using receiver operating characteristic (ROC). Also the FES-I score of groups based on expanded disability status scale (EDSS) 1-3.5 low and 4-6 moderate, time up and go (TUG) ≥14 sec and functional reach test (FRT) ≥25 cm were compared. The correlation between FES-I with EDSS, TUG, FRT and short form health survey (SF-36) was assessed., Results: The ROC curve analysis revealed that the FES-I could differentiate people with MS based on fall history at a cutoff score of 35.5. The area under the curve (AUC) was 0.86 (sensitivity 76%; specificity 95%). Significant difference was observed between the FES-I score of groups with moderate and low EDSS scores (d = 2.98), higher than 14 sec TUG (d = 2.18) and lower than 25 cm FRT(d = 2.53). Significant high correlation was observed between FES-I with TUG (r = 0.88), EDSS (r = 0.91), FRT (r = -0.83), SF-36 physical (r =  -0.87) and mental (r =  -0.70) subscales., Conclusions: The Persian versions of the FES-I could differentiate people with MS with fall history, higher disability, lower functional mobility and balance deficiency., Competing Interests: Declaration of Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with unknown etiology, which typically is manifested in early to middle adulthood. Recently, genome-wide association studies have identified susceptibility of immune-related genes to be involved in MS predisposition. The goal of the current study was to investigate the association of single nucleotide polymorphisms (SNP) with the immunologically related genes responsible for the disease, composed of CD58 (rs2300747 A>G), CD226 (rs763361 C>T), and HLA-G (rs1611715 A>C), with MS susceptibility. In this case-control study, a total of 200 patients suffering from relapsing-remitting multiple sclerosis and 200 healthy individuals were recruited. DNA was extracted from blood and then all subjects were genotyped for the polymorphism within mentioned genes by high-resolution melting (HRM) real-time PCR method. Statistical analyses were performed using SPSS software (version 20; SPSS, Chicago, IL, USA). Our finding showed that there are significant differences in genotype and allele frequencies between two groups regarding rs763361 (P = 0.035, OR 0.64, CI 95% for C allele) and rs1611715 (P = 0.038, OR 1.57, CI 95% for AA genotype) polymorphisms within CD226 and HLA-G genes, respectively. Concerning rs2300747 polymorphism on CD58 gene, no significant differences were found between cases and controls. In general, results from the current study indicate that CD226 and HLA-G, but not CD58 genetic polymorphisms are associated with increased risk of MS in Isfahan population similar to European populations. However, to elucidate how these SNPs contribute to MS pathogenesis, functional studies are needed.

Background/aim: Gut microbiota plays an important role in colorectal cancer (CRC) and its composition in CRC patients can be influenced by ethnicity and tumour genomics. Herein, the aim was to study the possible associations of ethnicity and gene mutations with the gut microbiota in CRC patients., Materials and Methods: Bacterial composition in stool samples of 83 CRC patients and 60 controls from Iran and Finland was studied by 16S rRNA gene sequencing. The association of gut microbiota composition with CRC, host mutations in KRAS, NRAS and TP53, and ethnicity analysed., Results: Beta diversity analysis indicated significant differences between the Iranian and Finnish gut microbiota composition, in both controls and patients' groups. The Iranian controls had higher abundance of Prevotella and lower abundance of Bacteroides compared to the Finnish controls, while the Finnish patients had higher abundance of Clostridium compared to Iranian patients. Abundance of Ruminococcus was higher in patients compared to the controls. Higher abundances of Herbaspirillum, Catenibacterium and lower abundances of Barnesiella were associated with mutations in NRAS, TP53, and RAS respectively., Conclusion: A possible link of host gene mutations with gut bacterial composition is suggested., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Cancer-related Fatigue (CRF) is one of the most common complications of acute myeloid leukemia (AML) and its related therapies. It can influence all physical and psychological aspects of the patient’s life. Also, it is believed that exercise can improve CRF in patients with cancer. Objective: This study aimed to investigate the effect of the walking exercise program on CRF in patients with AML undergoing chemotherapy. Methods: In this quasi-experimental study with a pre- and post-test design, 50 patients with AML undergoing chemotherapy were selected using a convenience sampling method at a teaching hospital in an urban area of Iran. The intervention included daily 30 minutes of planned walking for ten days. Data was collected using a demographic data form and the Brief Fatigue Inventory, which were filled out before the intervention, and on the fifth and tenth days of the intervention. Findings: Statistically significant differences were reported in the reduction of CRF on the fifth day and tenth day of the intervention (p <0.001). Conclusions: The planned walking intervention can be used as an easy and low-cost method for reducing CRF in patients with leukemia.

Background: Colorectal cancer (CRC) is rated as the second cause of cancer death. Genetic determinants are considered as driving forces in the development of sporadic CRC. Single-nucleotide polymorphisms (SNPs), due to their abundance in the human genome with collectively huge effect on cellular signaling pathways, are attributed as the main genetic factor in disease susceptibility including cancers. MicroRNAs are contributing to posttranslational gene regulation. They exert their regulatory function by binding to their specific recognition sequences located at 3'-untranslated region (UTR) of mRNAs. In the present study, we have elucidated the role of rs12904, a naturally occurring SNP, in the recognition site of miR200c in the 3'UTR of ephrin A1 ligand gene, in the development of sporadic CRC in the Iranian population., Materials and Methods: A case-control study using 152 CRC patients and 160 noncancerous counterparts was conducted to determine the rs12904 genotypes using polymerase chain reaction-restriction fragment length polymorphism method., Results: The results revealed no significant association between the rs12904 and sporadic CRC (odds ratio = 0.97, 95% confidence interval = 0.70-1.34). The frequency of genotypes and also alleles of the mentioned polymorphism were not significantly different between case and control groups (P = 0.765 and P = 0.847, respectively)., Conclusion: The results suggest that this polymorphism probably has not a crucial role in the Iranian CRC risk and is not an important potential risk factor in molecular diagnostics of mentioned disease among the Iranian population., Competing Interests: None

Objective Hearing loss (HL) is the most common sensory-neural defect and the most heterogeneous trait in humans, with the involvement of >100 genes, which make a molecular diagnosis problematic. Next-generation sequencing (NGS) is a new strategy that can overcome this problem. Study Design Descriptive experimental study. Setting Diagnostic laboratory. Subjects and Methods A comprehensive family history was obtained, and clinical evaluations and pedigree analysis were performed in a family with multiple individuals with HL. As the first tier, GJB2 was sequenced, and genetic linkage analysis of DFNB1A/B was performed to rule out the most common cause of the disease. Targeted NGS was used to unravel the molecular etiology of the disease in the HL-associated genes in the proband. Two homozygous variants remained in OTOF after proper filtration. Cosegregation and in silico analysis were done. Preimplantation genetic diagnosis (PGD) was accomplished via linkage analysis and direct sequencing of the pathogenic variant. Results Clinical evaluations suggested autosomal recessive nonsyndromic HL. Two homozygous variants, c.367G>A (p.Gly123Ser) and c.1392+1G>A, were identified in cis status. c.1392+1G>A met the criteria for being pathogenic according to the variant interpretation guideline of the American College of Medical Genetics and Genomics. PGD was successfully performed to prevent the recurrence of the disease in the related family. Conclusion A novel OTOF mutation causing HL was identified. Here, we report the effectiveness of the combined application of targeted NGS and PGD in diagnosis and prevention of hereditary HL.

Despite advances in treatment, children with acute lymphoblastic leukemia (ALL) still experience drug resistance and relapse. Several gene mutations are involved in the onset of this disease and resistance to therapy. The present study examines the incidence of IKZF1, CDKN2A/B, PAX5, EBF1, ETV6, BTG1, RB1, JAK2, and Xp22.33 gene deletions/duplications associated with pediatric ALL in Iran and investigates the possible effect of these mutations on drug resistance. Three-year disease-free survival (3DFS) was evaluated for children diagnosed with Philadelphia negative precursor-B-cell ALL hospitalized at Sayed-al-Shohada Hospital, Isfahan-Iran, from January 2009 until December 2012. DNA was extracted from bone marrow slides, and ALL correlated gene deletions and duplications were measured using Multiplex Ligation-dependent Probe Amplification (MLPA) method. The correlation between gene mutations and 3DFS was then assessed. Among the nine aforementioned investigated genes, 63% of samples showed at least one gene mutation. At least two concomitant genomic mutations were observed in 42% of samples. Pax5 deletion was the most prevalent gene mutation observed in 45% of cases, and showed significant negative impact on response to treatment. CDKN2A/B (9p21.3) gene deletion, and ETV6 (12p13.2) gene duplication also demonstrated negative effect on patient survival and contributed to a worse prognosis if concomitant with Pax5 gene deletion. ALL patients with one of the gene deletions including Pax5  and CDKN2A/B (9p21.3) or ETV6 (12p13.2) gene duplication are classified as high-risk patients and need more intensified protocols of treatment to improve their chance of survival.

T-cell immunoglobulin and mucin domain (TIM)-3 have been shown to negatively regulate Th1 cell-mediated immunity. Activation of TIM-3 by galectin-9 induces Th1 cell apoptosis, which may contribute to skewing of immune response towards Th2-dominant immunity. The aim of this study was to determine whether certain genetic variations of TIM-3 influence predisposition to asthma in a sample of Iranian population. This case-control study was conducted on 209 patients with asthma and 200 healthy controls. The +4259 T>G and -574 G>T polymorphisms were detected using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and amplification refractory mutation system-PCR(ARMS-PCR). Total serum IgE was further measured with ELISA. Notably, +4259T > G and-574G>T polymorphisms of TIM-3 were significantly associated with the susceptibility to asthma. In addition, the present study showed a significant difference between the distribution frequency of the GT + TT genotype and T allele on the +4259 T>G and -574 G>T locus between the groups.However, no correlation between the +4259 T > G and -574G > T polymorphisms and total serum IgE levels were observed. Together these results suggest that the TIM-3 +4259 T>G and -574 G>T polymorphisms are greatly associated with the susceptibility of Iranian population to asthma, which could open up new horizons for  better understanding of the pathophysiology, diagnostic, prognostic and therapeutic approaches of asthma.

Background: Nordic is one of the most popular questionnaires for evaluating Work-related Musculoskeletal Disorders (WMSDs), but no studies have been reported on the reliability and validity of this questionnaire in Iran., Objective: The aim of this study was translation, cross-cultural adaptation and validation of the Persian version of the Specific Nordic questionnaire (SNQ), and evaluation of the reliability of this questionnaire for the assessment of WMSDs in Iranian industrial workers., Methods: The SNQ was completed by 122 Iranian industrial workers with lumbar or knee musculoskeletal disorders to assess the reliability and construct validity. The validity was assessed by knee injury and Osteoarthritis Outcome Score (KOOS) and Oswestry Disability Index (ODI) questionnaires. Reliability was assessed by a test-retest procedure for 60 patients with 7-days interval., Results: There was significant positive correlation between KSNQ and KOOS pain (r = 0.71, p < 0.05) and the KSNQ and KOOS QOL (r = 0.72, p < 0.05). There was High Pearson correlation between LSNQ and ODI (r = 0.77, p < 0.05). Both lumbar and knee SNQ had a high Kappa coefficient correlation (0.83-1 for KSNQ and 0.63-1 for LSNQ)., Conclusions: The Persian version of the SNQ is a reliable and valid instrument to be used for the assessment of WMSDs in Iranian industrial workers.

Objective: SCN5A encodes alpha subunit of the major sodium channel (Nav1.5) in human cardiac tissue. Malfunction of this cardiac sodium channel is associated with a variety of cardiac arrhythmias and myocardial inherited diseases., Methods: Fifty-three members from three families each diagnosed with long-QT syndrome type 3 (LQTS3), Brugada syndrome (BrS), or sick sinus syndrome (SSS) were included in this observational, cross-sectional study. In this study, we analyzed the sequences of coding region of the SCN5A gene., Results: Eleven members of the LQTS family (39%) showed p.Gln1507-Lys1508-Pro1509del mutation, 8 of BrS family (50%) showed p.Arg222Ter nonsense mutation, and 5 of 9 SSS family members (55%) showed a novel p.Met1498Arg mutation in the SCN5A gene., Conclusion: p.Gln1507-Lys1508-Pro1509del mutation, p.Arg222Ter nonsense mutation, and p.Met1498Arg in LQTS, BrS, and SSS, respectively, are reported for the first time in the Iranian population. Information regarding underlying genetic defects would be necessary for verifying certain clinically diagnosed arrhythmia types, carrier screening in affected families, and more precise therapy of the patients are required.

Cystinuria is an autosomal inherited disorder of renal reabsorption of cystine, arginine, lysine, and ornithine. Increased urinary excretion of cystine results in the formation of kidney stones. Considering the few studies on the genetic basis of the cystinuria in the Middle East and the population-specific distribution of mutations in the SLC3A1 and SLC7A9 genes, in the present study, mutation analysis of these two genes was performed in a cohort of Iranian patients with cystinuria. Thirty unrelated cystinuria patients were analyzed for four of the most common mutations using ARMS-PCR (M467T, T216M) and RFLP-PCR (G105R, R333W) methods. For negative sample, two exons of both genes, which harbor many mutations, were subject to DNA sequencing. Eight variants were identified including missense, polymorphism, intron variant, and a novel variant. The most frequent mutations were not detected in our patients and only G105R was found. Since the molecular genetic testing results may influence the therapy and prognosis of cystinuria, this paper contributes to understanding of the molecular basis of cystinuria in the Iranian patients.

Purpose: Microsatellite instability (MSI) and mismatch repair (MMR) gene expression present a hallmark mutational signature of Lynch syndrome as a common hereditary cancer predisposing condition. Since there is not enough data of molecular and clinicopathological aspects of the disease in Iranian populations, this article is a new description in Central Iran., Methods: It is a descriptive analytical study in which we screened 1659 colorectal cancer (CRC) patients based on early-onset disease and Amsterdam II criteria during 14 years (2000-2013). MSI testing was applied through a commercial kit evaluating five mononucleotide markers (BAT-25, BAT-26, MON0-27, NR-21, and NR-24) using a fluorescent multiplex PCR method. Immunohistochemistry (IHC) staining was set up to detect expression of four mismatch repair (MMR) genes including MLH1, MSH2, MSH6, and PMS2. SPSS 16 software was used to analyze the data., Results: Overall, 31 of 45 screened at-risk families were eventually included to MSI testing of which 9/31 patients (∼29 %) showed MSI in their tumor tissues including 6 (19.4 %) MSI-H (high). BAT-26 was the most instable marker with instability in 7/31 MSI tumors (22.6 %). IHC-MMR staining was absent in 7/31 probands (22.6 %) of which in 4 cases, both MSH2/MSH6 (57.1 %) and, in 2 cases, both MLH1/PMS2 showed deficiency (28.6 %), and just in one case, MSH6 was defective (14.3 %). IHC-MMR was absent in all 6 MSI-H tumors while none of 3 MSI-L tumors were MMR-deficient. Just single MSH6-defective tumor showed MSS state. The frequency of CRC among MMR-deficient and MMR-proficient families was 67.5 and 27.9 %, respectively. The most common extracolonic cancer among both MMR-deficient and MMR-proficient groups was stomach, respectively, with 26.7 and 16.5 %., Conclusions: A different molecular and clinicopathological phenotype of tumors in CRC Iranian patients at risk for Lynch syndrome could suggest some new molecular mechanisms about which more evaluations are necessary.

Purpose: To identify the ability of the Persian-version of the Shoulder Pain and Disability Index (SPADI) and the Disabilities of the Arm, Shoulder, and Hand (DASH) to detect changes in shoulder function following physiotherapy intervention (i.e. responsiveness) and to determine the change score that indicates a meaningful change in functional ability of the patient (i.e. Minimally Clinically Important Difference (MCID))., Method: A convenient sample of 200 Persian-speaking patients with shoulder disorders completed the SPADI and the DASH at baseline and then again 4 weeks after physiotherapy intervention. Furthermore, patients were asked to rate their global rating of shoulder function at follow-up. The responsiveness was evaluated using two methods: the receiver operating characteristics (ROC) method and the correlation analysis. Two useful statistics extracted from the ROC method are the area under curve (AUC) and the optimal cutoff point called as MCID., Results: Both the SPADI and the DASH showed the AUC of greater than 0.70 (AUC ranges = 0.77-0.82). The best cutoff points (or change scores) for the SPADI-total, SPADI-pain, SPADI-disability and the DASH were 14.88, 26.36, 23.86, and 25.41, respectively. Additionally, moderate to good correlations (Gamma = -0.51 to -0.58) were found between the changes in SPADI/DASH and changes in global rating scale., Conclusions: The Persian SPADI and DASH have adequate responsiveness to clinical changes in patients with shoulder disorders. Moreover, the MCIDs obtained in this study will help the clinicians and researchers to determine if a Persian-speaking patient with shoulder disorder has experienced a true change following a physiotherapy intervention. Implications for Rehabilitation Responsiveness was evaluated using two methods; the receiver operating characteristics (ROC) method and the correlation analysis. The Persian SPADI and DASH can be used as two responsive instruments in both clinical practice and research settings. The MCIDs of 14.88 and 25.41 points obtained for the SPADI-total and DASH indicated that the change scores of at least 14.88 points on the SPADI-total and 25.41 points on the DASH is necessary to certain that a true change has occurred following a physiotherapy intervention.

Purpose: To culturally translate and validate the Community Integration Questionnaire (CIQ) in persons with multiple sclerosis (MS)., Methods: After a forward-backward translation, 105 persons with MS completed the Persian versions of the CIQ and MS Quality of Life (MSQOL) questionnaires in the first visit. The CIQ was re-administered to a sample of 45 persons with MS 7-10 days after the first session. Test-retest reliability and internal consistency were assessed using intraclass correlation coefficient (ICC) and Cronbach's α coefficient, respectively. Construct validity was assessed by measuring associations between subscales of the Persian CIQ (including Home Integration (HI), Social Integration (SI), and Productivity (P)) and MSQOL (including Physical and Mental Components). Dimensionality was assessed through two methods of corrected item-subscale correlation and factor analysis., Results: The acceptable level of test-retest reliability (ICC ≥0.70) was obtained for the Persian CIQ. However, Cronbach's α coefficient of ≥0.70 was only seen for the HI. The correlations between the Persian CIQ and the Physical MSQOL were higher than those of Persian CIQ and the Mental MSQOL. The corrected item-subscale Spearman's correlation coefficient of 0.40 was exceeded by most items of the HI and 2 items of P. A total of four factors were detected and similar to the results of item-subscale correlation, the most variability was seen for the items of SI which loaded on different factors., Conclusions: Persian CIQ seems to be a reliable and valid instrument for monitoring the level of community integration following rehabilitation in persons with MS. Some modifications need to be made in the SI of the Persian CIQ to improve extraction of information regarding community integration of persons with MS.

Prosthetic mechanical valves have a high risk condition for patients in pregnancy. The aim of this study was to evaluate the safety of pregnancy in mothers with prosthetic heart valves. In this cross sectional study, we compared incidence of thromboembolic attacks abortion and maternal and fetal complications in 19 patients with prosthetic heart valves. We reviewed medical records, also office visit and follow up of these women for 10 years. Between 10 years we studied 19 patients, 13 had mechanical heart valves with mean ages of 28.2 +/- 5.43, 4 cases with bioprosthetic valves with mean age of 25.4 +/- 4.12 and 2 cases of valve repaired 27.00 +/- 7.07. Seven women were uniparous 8 cases were in second pregnancy, one had 3rd and another one were gravid 4th. There was a mean interval between valve surgery and pregnancy of 7.65 +/- 6.07 (1-23) years. Dominant underling disease for valve replacement was rheumatic. In conclusion bridge anticoagulation during pregnancy is safe for mother and fetus in women with mechanical heart valves.

Rheumatic mitral valve stenosis continues to be the most frequently encountered clinically significant valvular abnormality in pregnant women. We retrospectively studied the fetal outcomes of patients with severe rheumatic Mitral Valve Stenosis (MS) admitted to hospital with heart failure and underwent Percutaneous Balloon Mitral Valvotomy (PBMV) during pregnancy. We identified all of the pregnant cases with rheumatic MS from February 1st 1994 till February 1st 2011 who underwent PBMV from medical records in the tertiary referral center of Madani Heart Hospital in Tabriz, Iran. Follow up was done by phone call and office visit. During this period 24 pregnant patients with mean ages of 29.45 +/- 5.05 (19-38) had undergone PBMV for severe MS. Fourteen patients could not be reached and were lost to follow-up. PBMV had been performed during second trimester of pregnancy in 20 cases (83.3%) and during third trimester in 4 patients (16.6%). The success rate of PBMV was 100%. Pulmonary artery pressure reduced from 58.88 +/- 21.97 to 38.50 +/- 8.87 (p < 0.05), peak and mean transmitral valve gradient reduced 25.20 +/- 9.71 to 11.03 +/- 3.61 (p < 0.0001), 14.18 +/- 7.60 to 5.00 +/- 1.39 (p = 0.004), respectively. We conducted follow up in 10 patients with good fetal outcome in all except in 2 infants who died during follow up with intractable heart failure. Twenty patients were in normal sinus rhythm at the time of procedure (83.3%) and 4 of them (16.7%) had arterial fibrillation. PBMV during pregnancy could be recommended as a relatively safe procedure for mother and fetus.

The present study aimed at evaluating coronary risk factors in women with definite coronary artery disease. This prospective study was conducted on 250 women with primary diagnosis of acute myocardial infarction or unstable angina. The patients were selected randomly using interview and registering the related risk factors. The primary diagnosis included 11.5% of myocardial infarction and 88.5% of unstable angina. All patients had risk factors. Diabetes was seen in 38.5%, hypertension in 78%, smoking in 27%, cholesterol > 150 mg in 98%, consumption of oral contraceptive in 57%, family history in 28% and limited physical activity in 2.6% of the patients. Body mass index of 59.6% of the patients was equal to or more than 27 kg m(-2). Also, 66.7% of the patients were post menopausal and history of premature hysterectomy was seen in 9.6% of the patients. There were 3 or more risk factors of coronary artery disease in most patients. Considering the known risk factors in women, dyslipidemia, premature menopause, hypertension, oral contraceptives, diabetes and smoking were regarded as the most common ones.

Background & Objectives: Leishmaniasis is a geographically widespread severe disease which includes visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL). There are 350 million people at risk in over 80 countries. In the Old World, CL is usually caused by Leishmania major, L. tropica, and L. aetiopica complex of which 90% of cases occur in Afghanistan, Algeria, Iran, Iraq, Saudi Arabia, Syria, Brazil and Peru. Recently, Eslami et al (2011) reported a novel TRYP6 gene encoding tryparedoxin peroxidase from an Iranian L. major strain exhibiting homology with the related gene in a divergent genus of Kinetoplastida, the Crithidia. This prompted us to analyze the mentioned gene in 100 isolates obtained from patients with suspected CL. Consequently, we analyzed internal transcribed spacer 1 (ITS1) region, RNA polymerase II largest subunit (RPOIILS) and the mitochondrial DNA polymerase beta (DPOLB)., Methods: After obtaining samples from 100 patients, DNA extraction was performed and TRYP6 was analyzed using conventional PCR. All samples harbouring TRYP6 with smaller size (555 bp) were analysed based on three other regions: ITS1, RPOIILS and DPOLB genes., Results: Results showed that 10% of the isolates have the same character as observed in our previous study. The ITS1-RFLP-PCR of this 10% isolates showed their similarity to the one from Crithidia fasciculata. RNA polymerase II largest subunit (RPOIILS) showed genetic diversity but the mitochondrial DNA polymerase beta (DPOLB) did not show any genetic diversity., Conclusion: This study might also help in solving the problems concerning Leishmaniasis outbreaks currently reported in Iran and some other endemic regions of the world.

Colorectal cancer (CRC) is among the major causes of cancer-related morbidity, mortality, and human health problem worldwide. Single-nucleotide polymorphisms (SNPs) in different genes are reported to be effective in increased risk of CRC in different ethnic population. We conducted a case-control study in patients diagnosed with sporadic colorectal cancer (n = 115) and healthy controls based on colonoscopy evidences (n = 120).In this replicative study, we aimed to investigate the association of two previously reported polymorphisms, rs6983267 and rs4444903, with sporadic colorectal cancer in a subset of Iranian patients. Genotyping was performed via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. A significant relation was found between rs6983267 variant in the 8q24 region and colorectal cancer. The distribution of G/G genotypes among sporadic CRC patients was more frequent than that in the control group (P value = 0.001). The frequency of the G allele in the colorectal cancer patient group was also higher than that in the control group (65% vs. 48%; P value = 0.001). Compared with GG genotype, individuals with G/T and T/T genotypes had lower risk to develop sporadic CRC (OR = 0.357, 95% CI = 0.201-0.635). For the rs4444903 SNP, no significant association (P value = 0.149) was found with colorectal cancer risk. In conclusion, our findings suggest that the 8q24 rs6983267 SNP may play a pivotal role in the development of sporadic CRC in Iranian population. Therefore, it may be included as a potential genetic susceptibility marker for sporadic CRC.

Diabetes is one of the most common and challenging health problems. Studies in several nations show that polymorphisms within the transcription factor 7-like 2 genes could be associated with type 2 diabetes (T2D). Therefore, a case-control study was conducted to find the association between SNP rs7903146 and T2D in our population. The study consists of 110 patients referring to clinic and 80 healthy controls randomly selected based on WHO guideline. DNA was extracted from blood and genotyped by PCR-RFLP with specific primers to amplify a fragment for restriction enzyme (RsaI). A chi-square test was calculated to compare the proportions of genotypes or alleles. Using a logistic regression model, the odds ratio for risk of developing T2D was calculated with and without adjustment for age, sex, and BMI. The frequency of the T allele of rs7903146 (C/T) polymorphism was significantly higher in diabetic subjects (47.3%) compared to that in normal subjects (34.4%). Logistic regression analysis of the rs7903146 polymorphism showed that the odds ratio was 3.71(95% CI: 1.43-9.56; P: 0.008) for the TT genotype and 1.26 (95% CI: 0.67-2.39; P: 0.516) for the CT genotype when compared with the CC genotype. Odds ratio adjusted for age, sex, and BMI have shown similar results. The results show that rs7903146 of TCF7L2 gene is an important susceptibility gene for T2D mellitus in the province of Isfahan, Iran. Our results support the recent findings that rs7903146 of TCF7L2 gene is an important genetic risk factor for the development of T2D in multiple ethnic groups.

Colorectal cancer (CRC) is one of the leading cancers worldwide. Through genome wide association studies, several single nucleotide polymorphisms scattered in the genome emerged to be influential in the development of sporadic CRC in some populations. However, replicative studies failed to prove a particular SNP-CRC association in populations and ethnic groups. Cyclooxygenase-2 (PTGS2) is a crucial enzyme involved in the metabolism of prostaglandins. The aim of this replicative study is to investigate the possible association between PTGS2 -765G>C polymorphism and sporadic CRC risk in a subset of Iranian population. A total of 110 patients with sporadic CRC, and 120 controls were genotyped for PTGS2 -765G>C polymorphism by using polymerase chain reaction-based restriction fragment length polymorphism. There were no significant differences in the genotype and allele frequencies of PTGS2 -765G>C between two groups except in irregular aspirin or non-steroidal anti-inflammatory drugs (NSAID) consumers. Frequencies of genotypes and alleles were as follows: GG = 44.2, GC = 48.3, CC = 7.5%, in controls and GG = 34.55, GC = 60.9, CC = 4.55% in cases. Regarding the allele frequency, the following values were found: G = 65, C = 35% in cases and 68.3, 31.7% in the controls, respectively. In irregular aspirin or NSAID consumers combined GC+CC genotype was found to be a risk genotype (OR = 1.933, 95% CI: 1.067-3.501, P = 0.036). Overall, no significant relation was found between this polymorphism and sporadic CRC in Iranians. However, in irregular aspirin or NSAID consumers the combined GC+CC genotype proved to be a risk genotype.

Purpose: To culturally translate and validate the Persian version of Kujala Patellofemoral Scale (KPS) and evaluate the test-retest reliability, internal consistency, construct validity and ceiling or floor effects of this instrument in patients with patellofemoral pain syndrome (PFPS)., Method: After standard forward and backward translations, 100 patients with PFPS completed the Persian versions of the KPS and Short-Form 36 Health Survey (SF-36) in the first visit. With time interval of 2-3 days after the first visit, 47 patients filled out the KPS in the second visit. Test-retest reliability and internal consistency were assessed using intraclass correlation coefficient (ICC(2,1)) with 95% confidence interval (95% CI) and Cronbach's α coefficient, respectively. The Spearman's rank correlation (r(s)) was used to assess the correlations between the Persian KPS and SF-36 subscales., Results: The acceptable level of ICC >0.70 (ICC = 0.96, 95% CI = 0.93-0.98) and Cronbach's α coefficient >0.70 (α = 0.81) was obtained for the Persian KPS. There were low to moderate correlations (r(s) = 0.25-0.60, p < .01) between the Persian KPS and Persian SF-36 subscales of mental and physical health components. However, correlations between the Persian KPS and SF-36 physical components were higher than correlations between the Persian KPS and SF-36 mental components. No ceiling and floor effects were seen for the Persian KPS., Conclusions: The Persian version of KPS is a reliable and valid outcome measure of disability and seems to be a suitable instrument for use in clinical practice of Iranian patients with chronic PFPS.

Beta-thalassemia (beta-thal) is one of the most common autosomal recessive disorders in Iran, with more than 15,000 registered cases of thalassemia major in the country. Iran has a multiethnic society and knowledge of the mutation spectrum and regional distribution is an essential requirement for health planning and a prenatal diagnosis program. We have determined the spectrum of mutations in patients from the Isfahan region of Iran. A study of 190 chromosomes revealed 24 different mutations, including three novel ones: -41 (A>C), IVS-I-109 (-T) and codon 24 (-G). The most common mutation was IVS-II-1 (G>A) (20.5%), followed by IVS-I-5 (G>C) (11%). The findings for the Isfahan region confirm the extremely heterogeneous nature of the molecular basis of beta-thal in Iran. The results show that a strategy of using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) for 14 of the most common mutations and DNA sequencing for the rare mutations can be used for prenatal diagnosis of beta-thal in this region.

Cryptosporidium is an important protozoan that cause diarrheal illness in humans and animals. Different species of Cryptosporidium have been reported and it is believed that species characteristics are an important factor to be considered in strategic planning for control. We therefore analyzed oocysts from human and animal isolates of Cryptosporidium by PCR-RFLP to determine strain variation in Isfahan. In total, 642 human fecal samples from children under five years of age, immunocompromised patients, and high risk persons and 480 randomly selected rectal specimens of cows and calves in Isfahan were examined. Microscopic examination showed that 4.7% (30/642) of human samples and 6.2% (30/480) of animal samples were infected with Cryptosporidium. After identification of the samples infected with the parasite, oocysts were purified and their DNA was extracted. We used PCR-RFLP analysis of a 1750-bp region of 18S rRNA gene to identify Cryptosporidium species. The human samples were infected with Cryptosporidium parvum II, C. muris, C. wrairi, and a new genotype of Cryptosporidium (GenBank accession numbers: DQ520951). The cattle samples were identified as C. parvum II, C. muris, C. wrairi, C. serpentis, C. baileyi, and a new genotype of Cryptosporidium (GenBank accession numbers: DQ520952). Also we found a new genotype infecting both human and cattle samples (GenBank accession numbers: DQ520950). In addition to demonstrating the widespread occurrence of most species of Cryptosporidium, C. parvum, we also observed extensive polymorphism within species. Furthermore, the occurrence of the same species of parasite in both animal and human samples shows the importance of the animal-human cycle.