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Background: Vitiligo is a multifactorial depigmentation condition, which is due to skin melanocyte destruction. The increased expression of HLA class II genes in patients with pre-lesions of Vitiligo suggests an important role for the participation of immune response in the Vitiligo development. Recent studies progressively focused on HLA-DRB1 and DQB1 genes. In this study, we have evaluated the association and role of HLA-DRB4*01:01, -DRB1*07:01, and -DQB1*03:03:2 genes in different clinical subtypes of Vitiligo in the Iranian population.Methods: First, Genomic DNA from peripheral blood of 125 unrelated Vitiligo patients and 100 unrelated healthy controls were extracted through salting-out method. Then, HLA CLASS II genotyping were performed using sequence-specific primer PCR method. Finally, the clinical relevance of the testing for these genotypes were evaluated by applying the PcPPV (prevalence-corrected positive predictive value) formula.Results: Our results indicated the positive associations of DRB4*01:01 and DRB1*07:01 allelic genes with early-onset Vitiligo (P= 0.024 and 0.022, respectively). The DRB4*01:01 also showed a strong protection against late-onset Vitiligo (P= 0.0016, RR=0.360). Moreover, our data revealed that the DRB1*07:01 increases the susceptibility to Sporadic Vitiligo (P=0.030, RR=1.702). Furthermore, our findings proposed that elevated vulnerability of Vitiligo patients due to DRB4*01:01 and DRB1*07:01 alleles may be is correlated with the presence of amino acid Arginine at position 71 at pocket 4 on the antigen-binding site of the HLA-DRB1 receptor.Conclusion: Our findings on different subtypes of Vitiligo suggest that, despite a more apparent autoimmune involvement, a non-autoimmune nature for the etiology of Vitiligo could also be considered.

Summary Background Inflammatory bowel disease (IBD) is a lifelong condition with no cure. Patients with IBD might experience symptoms of common mental disorders such as anxiety and depression because of bidirectional communication via the gut–brain axis and chronicity of symptoms, and because of impaired quality of life and reduced social functioning. However, uncertainties remain about the magnitude of this problem. We aimed to assess prevalence of symptoms of anxiety or depression in adult patients with IBD. Methods In this systematic review and meta-analysis, we searched MEDLINE, Embase, Embase Classic, and PsycINFO for papers published from inception to Sept 30, 2020, reporting observational studies that recruited at least 100 adult patients with IBD and that reported prevalence of symptoms of anxiety or depression according to validated screening instruments. We excluded studies that only used a structured interview to assess for these symptoms and studies that did not provide extractable data. We extracted data from published study reports and calculated pooled prevalences of symptoms of anxiety and depression, odds ratios (OR), and 95% CIs. Findings Of 5544 studies identified, 77 fulfilled the eligibility criteria, including 30 118 patients in total. Overall, pooled prevalence of anxiety symptoms was 32·1% (95% CI 28·3–36·0) in 58 studies (I2=96·9%) and pooled prevalence of depression symptoms was 25·2% (22·0–28·5) in 75 studies (I2=97·6%). In studies that reported prevalence of anxiety or depression in patients with Crohn's disease and ulcerative colitis within the same study population, patients with Crohn's disease had higher odds of anxiety symptoms (OR 1·2, 95% CI 1·1–1·4) and depression symptoms (1·2, 1·1–1·4) than patients with ulcerative colitis. Overall, women with IBD were more likely to have symptoms of anxiety than were men with IBD (pooled prevalence 33·8% [95% CI 26·5–41·5] for women vs 22·8% [18·7–27·2] for men; OR 1·7 [95% CI 1·2–2·3]). They were also more likely to have symptoms of depression than men were (pooled prevalence 21·2% [95% CI 15·4–27·6] for women vs 16·2% [12·6–20·3] for men; OR 1·3 [95% CI 1·0–1·8]). The prevalence of symptoms of anxiety (57·6% [95% CI 38·6–75·4]) or depression (38·9% [26·2–52·3]) was higher in patients with active IBD than in patients with inactive disease (38·1% [30·9–45·7] for anxiety symptoms and 24·2% [14·7–35·3] for depression symptoms; ORs 2·5 [95% CI 1·5–4·1] for anxiety and 3·1 [1·9–4·9] for depression). Interpretation There is a high prevalence of symptoms of anxiety and depression in patients with IBD, with up to a third of patients affected by anxiety symptoms and a quarter affected by depression symptoms. Prevalence was also increased in patients with active disease: half of these patients met criteria for anxiety symptoms and a third met criteria for depression symptoms. Encouraging gastroenterologists to screen for and treat these disorders might improve outcomes for patients with IBD. Funding None.

Narcolepsy is a chronic neurological and a genetic disorder of autoimmune origin, which is characterized by five main symptoms, including excessive day time sleepiness, sudden loss of muscle tone or cataplexy, sleep paralysis, hypnagogic hallucinations, and disturbed nocturnal sleep. While there are several diagnostic tests for Narcolepsy such as MSLT (mean sleep latency test), polysomnography and low range of hypocretin in cerebrospinal fluid (CSF), sensitivity and specificity in these methodologies are not sufficient enough. Therefore, methods with higher sensitivity for the accurate diagnosis and confirmation of the disease are necessary.According to the infrequent prevalence of narcolepsy disease, we scheduled a case-control association study with 20 narcoleptic patients and 150 healthy individuals in a high-resolution HLA typing procedure employing SSP-PCR.Our study demonstrates that the DQB1*06:02 allele provides the highest susceptibility with absolute risk of 0.13%, for Narcolepsy (P = 1x10Thus, this can be proposed that the polymorphic differences in the epitope of the HLA receptor could contribute to their differential association with the Narcolepsy in Iranian population.

Background Lymphatic filariasis is a neglected tropical disease that can cause permanent disability through disruption of the lymphatic system. This disease is caused by parasitic filarial worms that are transmitted by mosquitos. Mass drug administration (MDA) of antihelmintics is recommended by WHO to eliminate lymphatic filariasis as a public health problem. This study aims to produce the first geospatial estimates of the global prevalence of lymphatic filariasis infection over time, to quantify progress towards elimination, and to identify geographical variation in distribution of infection. Methods A global dataset of georeferenced surveyed locations was used to model annual 2000–18 lymphatic filariasis prevalence for 73 current or previously endemic countries. We applied Bayesian model-based geostatistics and time series methods to generate spatially continuous estimates of global all-age 2000–18 prevalence of lymphatic filariasis infection mapped at a resolution of 5 km2 and aggregated to estimate total number of individuals infected. Findings We used 14 927 datapoints to fit the geospatial models. An estimated 199 million total individuals (95% uncertainty interval 174–234 million) worldwide were infected with lymphatic filariasis in 2000, with totals for WHO regions ranging from 3·1 million (1·6–5·7 million) in the region of the Americas to 107 million (91–134 million) in the South-East Asia region. By 2018, an estimated 51 million individuals (43–63 million) were infected. Broad declines in prevalence are observed globally, but focal areas in Africa and southeast Asia remain less likely to have attained infection prevalence thresholds proposed to achieve local elimination. Interpretation Although the prevalence of lymphatic filariasis infection has declined since 2000, MDA is still necessary across large populations in Africa and Asia. Our mapped estimates can be used to identify areas where the probability of meeting infection thresholds is low, and when coupled with large uncertainty in the predictions, indicate additional data collection or intervention might be warranted before MDA programmes cease. Funding Bill & Melinda Gates Foundation.

Background: Stomach cancer is a major health problem in many countries. Understanding the current burden of stomach cancer and the differential trends across various locations is essential for formulating effective preventive strategies. We report on the incidence, mortality, and disability-adjusted life-years (DALYs) due to stomach cancer in 195 countries and territories from 21 regions between 1990 and 2017. Methods: Estimates from GBD 2017 were used to analyse the incidence, mortality, and DALYs due to stomach cancer at the global, regional, and national levels. The rates were standardised to the GBD world population and reported per 100 000 population as age-standardised incidence rates, age-standardised death rates, and age-standardised DALY rates. All estimates were generated with 95% uncertainty intervals (UIs). Findings: In 2017, more than 1·22 million (95% UI 1·19-1·25) incident cases of stomach cancer occurred worldwide, and nearly 865 000 people (848 000-885 000) died of stomach cancer, contributing to 19·1 million (18·7-19·6) DALYs. The highest age-standardised incidence rates in 2017 were seen in the high-income Asia Pacific (29·5, 28·2-31·0 per 100 000 population) and east Asia (28·6, 27·3-30·0 per 100 000 population) regions, with nearly half of the global incident cases occurring in China. Compared with 1990, in 2017 more than 356 000 more incident cases of stomach cancer were estimated, leading to nearly 96 000 more deaths. Despite the increase in absolute numbers, the worldwide age-standardised rates of stomach cancer (incidence, deaths, and DALYs) have declined since 1990. The drop in the disease burden was associated with improved Socio-demographic Index. Globally, 38·2% (21·1-57·8) of the age-standardised DALYs were attributable to high-sodium diet in both sexes combined, and 24·5% (20·0-28·9) of the age-standardised DALYs were attributable to smoking in males. Interpretation: Our findings provide insight into the changing burden of stomach cancer, which is useful in planning local strategies and monitoring their progress. To this end, specific local strategies should be tailored to each country's risk factor profile. Beyond the current decline in age-standardised incidence and death rates, a decrease in the absolute number of cases and deaths will be possible if the burden in east Asia, where currently almost half of the incident cases and deaths occur, is further reduced. This study was funded by the Bill & Melinda Gates Foundation. AA is supported by Department of Science and Technology, Government of India, New Delhi through INSPIRE Faculty programme. FC and JF acknowledge support with funding from Fundacao para a Ciencia e a Tecnologia/Ministerio da Ciencia, Tecnologia e Ensino Superior (FCT/MCTES) through Portuguese national funds, through UID/MULTI/04378/2019 (FC), UID/QUI/50006/2019 (FC), and UID/Multi/50016/2019 (JF) grants. VMC acknowledges her grant (SFRH/BHD/110001/2015), received by Portuguese national funds through Fundação para a Ciência e Tecnologia (FCT), IP, under the Norma Transitória DL57/2016/CP1334/CT0006. APK is supported by the South African Medical Research Council. YJK is supported by Xiamen University Malaysia Research Fund (Grant No. XMUMRF/2018-C2/ITCM/0001). IMV is supported by the Sistema Nacional de Investigación (SNI), Panama.

Multiple sclerosis (MS) is a neurodegenerative disease arising from interactions of both environmental and genetic factors. The SNP rs6897932 is located in IL‐7Ra gene associated with MS susceptibility in some population. In this study, we investigated the possible association of SNP rs6897932 with MS susceptibility in 157 Iranian MS patients and 152 healthy controls. We also studied genotype-dependent severity and response to IFN-β in MS. Unlike some previous studies, our results clearly demonstrate that there are no significant differences in distribution of the SNP rs6897932 in our chosen Iranian MS patients and controls. Furthermore our results show, Interferon beta (IFN-β) therapy over a period of two years demonstrated an IL‐7Ra genotype-dependent therapeutic effect in MS population. Patients carrying TT or TC genotypes gave a better response to IFN-β treatment, whereas patients carrying the homozygous CC genotype were the worst responders to IFN-β treatment. In other words, despite the lack of linkage the therapeutic response to the severity and progression of MS was related to the genotype of SNP rs6897932 presented in our patient. Therefore, in light of our findings reported here, to reach higher certainties, further studies are needed to associate IL-7Ra gene with the pathogenesis of MS. © 2019 Tehran University of Medical Sciences. All rights reserved. Acta Med Iran 2019;57(4):208-215.

Alzheimer's disease (AD) is a polygenic and multifactorial disease with a complex inheritance caused by the formation of amyloid plaques and neurofibrillary tangles in the brain. Increasing evidence indicates that many genes including interleukin-6 (IL-6) and alpha 2-macroglobulin (A2M) may contribute to the pathogenesis of AD. The A2M gene encodes α2-macroglobulin which specifically binds with the beta-amyloid peptides and prevents fibril formation. Protein of the IL-6 gene linked to beta-amyloid (βA) aggregation was detected in βA plaques in the brain of AD patients. The aim of the present study is to investigate the relationship of the IL-6 and A2M gene polymorphisms with AD and also the impact of rivastigmine on AD patients regarding their genotypes on IL-6 and A2M genes in 150 Iranian AD patients under rivastigmine therapy and 150 matched healthy controls. The results indicated that IL-6 G and C alleles had significant positive and negative association with AD, respectively, (P = 0.0001, relative risks (RR) = 1.39) and frequency of AD patients carrying IL-6 GG genotype was significantly in higher proportion in familial Alzheimer's disease (FAD) patients compared to controls (P = 0.02, RR = 2.25), and the IL-6 CC genotype was significantly protective against AD (P = 0.0003, RR = 0.65). Genotype analysis of A2M gene showed a significant positive correlation between A2M AA genotype and the AD patients (sporadic Alzheimer's disease (SAD) and FAD) (P = 0.001, RR = 1.56), proposing it as a possible risk factor for AD. Drug response from pharmacogenetic viewpoint after 3-year follow-up of AD patients and Clinical Dementia Rating (CDR) analysis demonstrated that AD patients carrying bigenic genotype IL-6 CC-A2M AG (ΔCDR = 4.5) and male patients with IL-6 CC genotype (ΔCDR = 3.83) provided the best response and the A2M GG genotype (ΔCDR = 7.97) and bigenic genotype IL-6 GG-A2M GG (ΔCDR = 8.5) conferred the worst response to the rivastigmine, suggesting likely involvement of genotype-specific response to rivastigmine therapy in AD patients. The results also propose that in view of the fact that C and G alleles created by nucleotide changes in the promoter region of IL-6 gene and this may affect the expression of the IL-6 gene and, hence, susceptible and protective role of GG and CC genotype in AD might be caused by higher and lower expression of IL-6 cytokine, respectively.

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are the most frequent muscular dystrophies. Present study aimed to determine the frequency of dystrophin gene alterations in Iranian DMD/BMD patients using molecular techniques. 146 Iranian DMD/BMD patients have been analyzed using two devised sets of multiplex polymerase chain reaction (M-PCR) followed by multiple ligation-dependent probe amplification (MLPA). Two isolated DMD and BMD patients were analyzed by DNA sequencing. 30.9 % of patients had single-exon deletion while group and contiguous exon deletions were identified in 41 % of the patients. The most numerous exon deletions included exons 45–50 and were identified in the first M-PCR set. Deletion detection rate was 99 % in first M-PCR set and remaining deletions (1 %) were identified in the second M-PCR set. MLPA analysis showed that there were two exons 3–5 and 41–43 duplications (1.4 %) in a BMD and a DMD patient, respectively. Two nonsense mutations including c.633dupA and c.6283 C>T were, respectively, found in a DMD and BMD patient in which c.633dupA has not ever been reported in DMD mutation database and was pathogenic mutation. Besides the report of frequency of dystrophin gene alteration in a subset of Iranian DMD/BMD patients, it was revealed that the proposed M-PCR protocol can be useful in the initial step of molecular diagnosis of DMD/BMD. Exon sequencing would be the final step in determining the mutation status of DMD/BMD patients following MLPA.

Summary Coeliac disease (CD) is a highly prevalent autoimmune disorder that is triggered by the ingestion of wheat gluten and related proteins in genetically susceptible individuals. The CD is associated with human leucocyte antigen (HLA) genes particularly with HLA-DQ alleles encoding HLA-DQ2 and DQ8 proteins. To define risk and severity alleles for CD, a total of 120 definite CD patients and 100 healthy controls were genotyped for HLA-DQB1 gene. HLA-DQB1 genotyping was performed in all patients and controls using PCR-SSP technique, and to evaluate the clinical relevance of testing for HLA-DQB1 and determining absolute risk of disease, prevalence-corrected positive predictive value and prevalence-corrected negative predictive value (PcPPV and PcNPV) were calculated. Our results for a first time show that DQB1*02:00 and DQB1*03:02 alleles and DQB1*02:01/03:02 genotype very significantly associated with increased risk of patients with CD, and DQB1*03:01,4 allele provides protection against CD in Iranian patients. Furthermore, the PcPPV for DQB*02:01 and 03:02 alleles in CD were 0.014 and 0.012, respectively, and the highest absolute risk presented by DQB*0201/0302 genotype (PcPPV = 0.079) and 98% of patients with CD carried DQB1*02:01/x or DQB1*03:02/x genotype. The results also clearly demonstrated that the DQB1*02:01 allele significantly associated with severity of CD, while DQB1*03:02 allele associated with mild form of CD. These results suggest that clinically suspected individuals for CD and first-degree relatives of patients with CD to be screened for HLA-DQB*0201 and DQB*0302 alleles for possible early diagnosis and treatments.

Aim The aim of the present study was to investigate the efficacy of Metformin compared with a hypocaloric diet on C-reactive protein (CRP) level and markers of insulin resistance in obese and overweight women with polycystic ovary syndrome (PCOS). Material and Methods Forty women with body mass index ≥ 27 and PCOS were randomly allocated to receive either Metformin or hypocaloric diet and were assessed before and after a treatment period of 12 weeks. High-sensitivity CRP (hs-CRP) and markers of insulin resistance (IR), homeostasis model assessment-IR, quantitative insulin-sensitivity check index and fasting glucose to insulin ratio were evaluated in each patient. Results A total of 10 subjects did not complete the trial (three patients in the Metformin group and seven patients in the diet group) and a total of 30 subjects completed the trial (17 subjects in the Metformin group and 13 subjects in the diet group). Serum concentration of hs-CRP significantly decreased in both the Metformin (5.29 ± 2.50 vs 3.81 ± 1.99, P = 0.008) and diet groups (6.08 ± 2.14 vs 4.27 ± 1.60, P = 0.004). There were no significant differences in mean hs-CRP decrement between the two groups. Decrease in hs-CRP levels was significantly correlated with waist circumference in the diet group (r = 0.8, P

Background Pyogenic bacteria and especially Staphylococcus aurous (S. aurous) are the most common cause of chronic osteomyelitis. Not only treatment protocol of chronic osteomyelitis occasionally is amiss but also this malady responds to treatment difficultly. Objectives This study investigates antibiotic resistance pattern of S. aurous isolated from Iranian patients who suffer from chronic osteomyelitis by two methods: disk diffusion (Kirby bauyer) and E-test (Epsilometer test) to find Vancomycin susceptibility and MIC (Minimum inhibitory concentration). Patients and Methods One hundred and thirty one patients who suffer from chronic osteomyelitis which have been referred to both governmental and private hospitals at 2010 were tried out for culturing of osteomyelitis site (sites). Antibiotic susceptibility and MIC of isolated bacteria were investigated by Kirby bauyer and E-test respectively. Results Samples were collected from bone (73.4%), surrounding tissue (14.6%) and wound discharge (12%). S. aureus was isolated from 49.6% of the samples. According to disc diffusion, methicillin resistance S. aureus (MRSA) was 75% and Vancomycin resistance S. aurous (VRSA) was 0% and based on MIC, MRSA was 68.5% and VRSA was 0%. According to MIC experiments, maximum sensitivity was against to Vancomycin (90.2%) and ciprofloxacin (54.4%) respectively but based on disc diffusion, maximum sensitivity was against to Vancomycin (97.7%) and ciprofloxacin (43.2%), respectively (P = 0.001). E-test (9.8%) in comparison with Disc diffusion (2.3%) showed higher percent of intermediate susceptibility to Vancomycin (P = 0.017). Conclusions Comparison of antibiograms and MICs showed that Kirby bauyer technique especially for detection of VISA strains is not reliable comparison with E-test. Already VRSA strains have not detected in Iranian chronic osteomyelitis, Thus Vancomycin is the first choice for chronic osteomyelitis empirical therapy in Iran yet.

Summary Type 1 Diabetes mellitus (T1D) is an autoimmune and multifactorial disease. HLA-DRB1 and DQB1 loci have the strongest association with T1D. This study aimed at investigating (i) susceptibility or protection of alleles, genotypes and haplotypes of HLA-DRB1 and DQB1 loci; and (ii) highly polymorphic amino acid residues of HLA-DRb1 and DQb1 in 105 Iranian T1D patients and 100 controls. The results indicated that DRB1*04:01, 03:01, D QB1*03:02, 02:01 a lleles, D RB1*

Background: The multifunctional cytokine interleukin-6 (IL-6) is involved in inflammatory processes in the central nervous system. It is well documented that amount of IL-6 is increased in serum, cerebrospinal fluid and central nervous system lesions of patients with multiple sclerosis. A single nucleotide polymorphism at position -174 in the IL-6 gene promotor appears to influence IL-6 expression. Recently, several researchers have focused on HLA-DRB alleles, specifically HLA-DRB1*1501, as a potential risk allele in the pathogenesis of multiple sclerosis. Objective: To investigate the possible influence of IL-6/-174 polymorphisms on susceptibility to multiple sclerosis and its integration with HLA-DRB1*1501. Genomic DNA was extracted from whole blood of 345 patients with multiple sclerosis and 426 control subjects. Method: The SSP-PCR method was used to determine genotypes and Fisher’s exact test was applied to determine differences between groups. HLA-DRB1*1501 was observed more frequently among multiple sclerosis patients compared with healthy subjects (45% and 34%, respectively; OR = 1.6, 95% CI = 1.2—2.2, p = 0.0018). At the IL-6/-174 position, the G allele had higher frequency among multiple sclerosis patients compared with controls (77% and 70%, respectively; OR = 1.4, 95% CI = 1.1—1.8, p = 0.0038). This difference was more significant among HLA-DRB1*1501-positive patients and controls (81% and 67%, respectively; OR = 1.9, 95% CI = 1.5—2.5, p < 0.0001). Results: Our results have shown that the G allele at the IL-6/-174 promoter polymorphism may be associated with development of multiple sclerosis in this population, and may be strengthened by HLA-DRB1*1501. Conclusions: We suggest more studies to confirm these results in other populations.

Summary Background. Vitiligo is an acquired idiopathic and polygenic disorder with progressive depigmentation of circumscribed patches. Its exact pathogenesis is unknown. The CD4 gene plays an important role in the cell-mediated immune response and its association with type 1 diabetes mellitus, which is an autoimmune disease, has been previously reported. Methods. Based on the assumption that autoimmunity is also involved in vitiligo, the CD4 gene was selected for study using a candidate gene approach. The pyrimidinerich pentanucleotide repeat length polymorphism located in the promoter of the gene was studied. We screened 144 unrelated Iranian patients with vitiligo and 144 healthy matched controls by PCR. Results. The CD4*A4 allele has a susceptibility association with the development of vitiligo in the Iranian population (OR = 1.68, 95% CI 1.18–2.42; P < 0.01, Pc = 0.02). When we compared CD4*A4-containing genotypes in the case and control groups, even more significant positive association was identified (OR = 2.02, 95% CI 1.26–3.22; P < 0.01 and Pc < 0.01). The CD4 gene polymorphism has a modest association with the development of vitiligo in Iranian patients.

The 32-base pair deletion on the C–C chemokine receptor 5 gene (CCR5-delta32) is known as a protective allele against immune system disorders. We have studied this variation in Iranian multiple sclerosis (MS) patients and healthy controls. DNA samples were prepared from the whole blood of 254 patients with MS and 380 healthy controls. We amplified the fragment including the CCR5-delta32 polymorphism and visualized the products in a documentation system after agarose gel electrophoresis. Data were analysed using one-way ANOVA and Fisher’s exact tests with SPSS-v13 and STATA-v8 software. The delta32 allele was more frequent in MS patients when compared with controls (OR = 2.3, P

Non-insulin-dependent diabetes mellitus has been recognized to be heterogeneous in etiology, with multiple subgroups. Several genes or chromosomal regions have been implicated in the development of the disease. In this study the association of HLA class II alleles and genotypes and the association of CD4 and CD3 polymorphisms were assessed in a large number of Belgian non-insulin-dependent diabetes mellitus patients. Furthermore, the importance of the DQ alpha 1Arg52/DQ alpha 1Arg52 and the DQ beta 1Asp57/DQ beta 1Asp57 genotypes and the combination of both genotypes were examined. Our results show that in the HLA class II genes only the DQ alpha 1Arg52+/DQ alpha 1Arg52+ genotype was significantly associated with non-insulin-dependent diabetes mellitus compared with controls (p = 0.011, RR = 2.02). We also observed that the frequency of the CD4*A4/*A8 genotype and the CD4*A7 allele was significantly increased and decreased respectively in non-insulin-dependent diabetes mellitus patients as compared with the controls (p = 0.018, RR = 2.16 and p = 0.0003, RR = 0.49 respectively). These results therefore suggest that HLA class II and CD4 genes might independently contribute to the susceptibility for non-insulin-dependent diabetes mellitus and that these alleles and genotypes might identify subgroups of patients with different susceptibilities.

Background Cystic fibrosis (CF) is the most common inherited disorder in Caucasian populations, with over 1400 mutations identified in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. Mutations in the CFTR gene may be also causative for CBAVD (Congenital Bilateral Absence of the Vas Deferens). The type and distribution of mutations varies widely between different countries and/or ethnic groups, and is relatively unknown in Iran. We therefore performed a comprehensive analysis of the CFTR gene in Iranian CF patients. Methods 69 Iranian CF patients, and 1 CBAVD patient, were analysed for mutations in the complete coding region, and its exon/intron junctions, of their CFTR genes, using different methods, such as ARMS (amplification refractory mutation system)-PCR, SSCP (single stranded conformation polymorphism) analysis, restriction enzyme digestion analysis, direct sequencing, and MLPA (Multiplex Ligation-mediated Probe Amplification). Results CFTR mutation analysis revealed the identification of 37 mutations in 69 Iranian CF patients. Overall, 81.9% (113/138) CFTR genes derived from Iranian CF patients could be characterized for a disease-causing mutation. The CBAVD patient was found to be homozygous for the p.W1145R mutation. The most common mutations were p.F508del (ΔF508) (18.1%), c.2183_2184delAAinsG (2183AA>G) (6.5%), p.S466X (5.8%), p.N1303K (4.3%), c.2789+5G>A (4.3%), p.G542X (3.6%), c.3120+1G>A (3.6%), p.R334W (2.9%) and c.3130delA (2.9%). These 9 types of mutant CFTR genes totaled for 52% of all CFTR genes derived from the 69 Iranian CF patients. Eight mutations, c.406-8T>C, p.A566D, c.2576delA, c.2752-1_2756delGGTGGCinsTTG, p.T1036I, p.W1145R, c.3850-24G>A, c.1342-?_1524+?del, were found for the first time in this study. Conclusions We identified 37 CFTR mutations in 69 well characterized Iranian CF patients, obtaining a CFTR mutation detection rate of 81.9%, the highest detection rate obtained in the Iranian population so far. These findings will assist in genetic counseling, prenatal diagnosis and future screening of CF in Iran.

Background & objectives Attention deficit hyperactivity disorder (ADHD) is a common heritable psychiatric disorder with a worldwide prevalence of 5%. The etiology of ADHD is still incompletely understood, but several studies, consistently indicate the strong role of genetic factors on this disorder. The aim of this study was to determine the effect of three SNPs rs11122319, rs11122330 and rs6675281 in the etiology of ADHD in an Iranian children. Methods In this research work, for the first time, we investigated the association of three SNPs (rs11122330, rs6675281 and rs11122319) in the DISC1 gene with ADHD in Iranian population. Two hundred fourthy subjects composed of 120 patients and 120 healthy controls were included and tetra-primer ARMS PCR technique was used for genotyping all selected SNPs. Results We found differences in genotype and allele distributions of rs 6675281 polymorphism between our patients and controls. The A, T and A alleles were the more frequent alleles in rs11122319, rs6675281 and rs11122330 polymorphisms in both case and control groups respectively. The TT genotype was more frequent in control group compared to patients. (P value = 0.008, OR= 1.5837, 95% CI= 1.1012 to 2.2776). Conclusion Our findings strengthens the role of DISC1 gene as a susceptibility locus for ADHD and indicate that rs6675281 polymorphism is a susceptibility factor for ADHD for the first time in children reported in an Iranian population in this part of the world.

Introduction: Postoperative visual loss (POVL) has become the focus of attention for anesthesiologists as a hallmark of perioperative management in spine surgery. A number of Intraoperative and postoperative factors has been documented but the exact etiology is still unclear. Nowadays, perioperative management and also complete curing of POLV is a big question of ophthalmologists and anesthesiologists. The purpose of this case report is to present a unique experience of complete curing the POLV. Case Presentation: Our patient was a 61-year-old man, with 75 kg weight and 180 cm height. The patient had no history of visual impairment except mild cataract in his right eye. The patient had a history of diffuse idiopathic skeletal hyperostosis (DISH). The patient had undergone lumbar surgery in prone position. The operation time was about 6 hours. About 30 minutes after transferring to postanesthesia care unit (PACU), patient was awake and complained of losing his eyesight. There was no vision and light perception in his right eye on primary examination. Urgent ophthalmologist consultation was requested. In ophthalmology examinations, the pupil reflex to light was absent in the right eye. After obtaining patients and his family informed consent, four hours after the operation, 40000 I.U. of recombinant human erythropoietin (rhEPO) was administered for patient in PACU (IV infusion, in 30 min). An ophthalmologist visited him every 6 hours after administration of rhEPO. The patient was transferred to intensive care unit (ICU) one hour later with total visual loss in the right eye. Ophthalmologic examination after the second dose of rhEPO, 30 hours after the operation, reported pupil reflex enhancement and light perception in his right eye. Finally the third dose of rhEPO (40000 I.U., IV infusion) was administered on the third day. Ophthalmologic examination after the third dose of rhEPO, 60 hours after the operation, reported normal pupillary light reflex of the right eye and visual acuity improvement to 20/20. The patient was discharged from hospital after six days, with normal visual acuity and without any new complications except surgical site pain. Conclusions: Our case report showed the therapeutic effect of rhEPO in complete curing of POVL. Regarding the side effects of EPO such as thrombogenic effects or mild hemodynamic changes like transient sinus tachycardia during infusion, it seems that beneficial effects of EPO is more than its disadvantages and expenses, for patients with POVL.

Introduction: Anesthesia in severe aortic stenosis, which describes a valve surface area less than 1 cm 2 , can result in rapid clinical deterioration and patient mortality. These patients may require treatment for aortic stenosis before any surgical intervention. In suitable patients percutaneous balloon aortic valvutomy appears to carry lower risk, but in emergency situations, it is important to determine which kind of anesthesia technique has the lowest risk for these patients, without any cardiac intervention. Case Presentation: In this case report, we present a patient who had tibia and fibula fractures and a symptomatic severe critical aortic stenosis which was diagnosed during a preoperative visit. The patient had exertional dyspnea, palpitations and fainting history, but he had not received any medical therapy before the present admission. During hospitalization and preoperative evaluation, a fat embolism occurred and the patient was admitted to the intensive care unit. Immediately after his recovery, we successfully managed the tibia and fibula fracture fixation without any cardiac intervention. Conclusions: Our anesthesia method was sciatic and femoral nerve block under double ultrasonic and nerve stimulator guidance.

Results: The prevalence of T. gondii antibody positive cases among patients showed differences between males and females. In the patient group, IgG was positive in 53.2% whereas, 41.4% of the control group had IgG positive (P = 0.02). Age at the time of diagnosis of schizophrenic patients with positive T. gondii IgG and IgM was significantly lower than other cases (34.2 ± 14.3 vs. 49.2 ± 11.7; P = 0.01). Patients with family members that had positive results for IgG ELISA test had higher probability for positive IgM seropositivity. Conclusions: Our results supported the longstanding hypothesis of correlation between T. gondii infection and schizophrenia. We also considered this infection as a possible etiological factor in the development of schizophrenia.

Background: Magnesium is an antagonist of (N-methyl D-Aspartate) NMDA receptor and its related canals, and may affect perceived pain. Objectives: The aim of this study was to evaluate the impact of intravenous magnesium on the hemodynamic parameters, analgesic consumption and ileus. Patients and Methods: A randomized, double blind, placebo controlled study was performed. Thirty two patients of ASA I or II, scheduled for major gastrointestinal (GI) surgery, were divided into magnesium and control groups. Magnesium group received a bolus of 40 mg/ kg of magnesium sulphate, followed by a continuous perfusion of 10 mg/kg/h for the intraoperative hours. Postoperative analgesia was ensured by Morphine patient-controlled analgesia (PCA). The patients were evaluated by Intraoperative hemodynamic parameters, the postoperative pain by numeral rating scale (NRS), and the total dose of intraoperative and postoperative analgesic consumption. Postoperative hemodynamic, respiratory parameters, physiological gastrointestinal obstruction (ileus), and side effects were also recorded. Results: The study included 14 males and 18 females. Age range of patients was 17 to 55 years old. The average age in the magnesium group was 41.33 ± 10.06 years and45.13 ± 11.74 years in control group. Mean arterial pressure (MAP) of magnesium group decreased during the operation but increased in control group (P < 0.001), and systemic vascular resistance (SVR) of magnesium group decreased during the operation also (P < 0.02) but increased in control group. Postoperative cumulative Morphine consumption in magnesium group, was significantly in lower level (P = 0.026). For NRS, severe pain was significantly lower, in magnesium group, at all intervals of postoperative evaluations, but moderate and mild pain were not lower significantly. Duration of postoperative ileus was 2.3 ± 0.5 days in magnesium group, and 4.2 ± 0.6 days in control group (P = 0.01). Conclusions: Intravenous magnesium reduces postoperative ileus, postoperative severe pain and intra/post operative analgesic requirements in patients after major GI surgery. No side effects of magnesium in these doses were seen, so it seems to be beneficial along with routine general anesthesia in major GI surgeries.

Background: Coronary artery disease (CAD) is the most common cause of death worldwide and many studies have been performed on reduction of its prevalence. Objectives: This case control study was designed to investigate the presence of Cytomegaloviruses, Chlamydia pneumoniae and Helicobacter pylori in atherosclerotic plaques of cadaveric coronary endothelium of patients with and without acute myocardial infarction. Patients and Methods: Sixty cadavers in two equal groups were analyzed. Acute myocardial infarction group included cadavers with acute myocardial infarction and atherosclerotic plaque. The non- acute myocardial infarction group included those with innocent atherosclerotic plaques in autopsy, expired due to other causes. Specimens from coronary vessels' atherosclerotic plaque were taken and studied by polymerase chain reaction for Cytomegaloviruses, C. pneumoniae and H. pylori. Results: Cadavers of 26 males and 34 females underwent autopsy procedures. Their mean age at the time of death was 48.17 ± 18.74 years. Unknown causes (20%), hanging (20%), head trauma (16.7%) and multiple traumas (13.3%) were the most common causes of death in the non- acute myocardial infarction group. PCR test results were negative for C. pneumoniae and H. pylori in all cadavers of both groups. Nine cadavers from the acute myocardial infarction group and one from the non- acute myocardial infarction group showed positive PCR results for Cytomegaloviruses (30% and 3.33%, respectively). There was a significant difference between the two groups regarding Cytomegaloviruses positivity in coronary artery plaques (P < 0.01, odd ratio: 12.42, 95% CI: 10.46 to 15.73). Conclusions: A significant proportion of coronary atherosclerotic plaques in cadavers with confirmed acute myocardial infarction were detected to be infected with Cytomegaloviruses while no infections of C. pneumoniae and H. pylori were detected.Coronary artery disease (CAD) is the most common cause of death worldwide and many studies have been performed on reduction of its prevalence.

In the present study the HLA-DRB and DPB1 alleles as well as CD4 and CD3 polymorphisms were tested in 100 Belgian schizophrenic patients and 204 controls. Our results indicate a significant negative association of the DPB1 0101 allele with schizophrenia (relative risk [RR] = 0.27). Furthermore a significant positive and negative association could be noticed for the CD4*A4 allele and CD4*A7/A8 genotype, respectively (RR 1.79 and 0.47, respectively). These findings suggest that some contribution of HLA class II and CD4 genes to an autoimmune-like pathogenesis in schizophrenia might exist.

Background/Aims: Alzheimer disease (AD) is a complex and genetically heterogeneous disorder, and certain genes such as PS2 and APOE4 contribute to the development of AD. Due to its heterogeneity, AD-predisposing genes could vary in different populations. Moreover, not all AD patients will respond to the same therapy. We specifically investigated the effect ofrivastigmine (Exelon) on PS2 and APOE genes in Iranian AD patients. Methods: A total of 100 AD patients, 67 patients with sporadic AD (SAD) and 33 patients with familial AD (FAD), receiving rivastigmine therapy and 100 healthy controls were studied.PCR-RFLP was used for genotyping of PS2 and APOE. Results: We found a positive association between the PS2 –A allele and SAD patients (pc = 0.01), and the PS2 +A/–A genotype was significantly more frequent in SAD than FAD patients (pc = 0.009). The APOE4 allele was associated with total AD, SAD and FAD (pc = 0.000002). Patients with the PS2 +A/–A genotype and bigenic genotypes of +A/–A·Ε3/Ε3 and +A/–A·Ε3/Ε4 were the best responders to Exelon therapy, and those with the PS2 +A/+A and APOE Ε3/Ε4 genotypes were the worst responders. Conclusion: Our findings suggest that the PS2 and APOE4 alleles and genotypes affect both AD risk and response to rivastigmine therapy.

Objective To discuss the classification systems and pose a rationale for a flexible approach. We also propose our surgical approach for vasoepididymal or epidymo-epididymal approximation. Polyorchidism is a rare congenital anomaly with about 200 cases reported. Methods We present 8 cases of polyorchidism treated at our institute from 1992 to 2010. To our knowledge, this is the most numerous single-center experience. We performed vasoepididymal or epidymo-epididymal approximation to restore near-normal anatomy plus stabilization of the testicular and ductal system to facilitate possible future reconstructive surgery. Results In the case of contralateral anorchia or an atrophic testis, a supernumerary testis can fairly replace the contralateral counterpart. The reproductive potential of the supernumerary testis must not be ignored. Also, the malignant potential of the supernumerary testis should not be overestimated. Conclusion A careful pursuit of the vessel and vasal route during surgery for an undescended testis, judicious use of laparoscopy, and a lower threshold for diagnosis both on imaging studies and during surgery might result in a greater number of cases of polyorchidism in the daily practice of pediatric urology.

Breast cancer is amongst the leading causes of death in women worldwide and the most common cancer amongst Iranian women. Unfortunately, the current clinical and histological criteria can only help 60 percent of women with breast cancer in diagnosis and long-term treatment. Therefore, genetic markers both at single gene and chromosomal level can play an important role in improving the diagnosis and prognosis of breast cancer patients. The aim of this retrospective study was to investigate the role of chromosome 1 and 8 copy number assessed by interphase fluorescence in situ hybridization (FISH), as prognostic parameters in 50 Iranian women, aged 35 to 64 years, with sporadic invasive ductal breast carcinoma. Chromosome 1 and 8 copy numbers were evaluated in relation to established clinicopathological parameters, the immunohistochemical markers ER, PR, P53 and cathepsin D, DNA index by flow cytometry, age and survival status of the patients. FISH using centromeric probes for chromosomes 1 and 8 was applied to interphase cell suspensions prepared from archived, Carnoyfixed tumor cells and selected paraffin-embedded tumor sections. Aneusomy for chromosomes 1 and 8 was present in all 50 patients to different levels. The total abnormality rate for chromosome 1 was 33.92 percent (4.24 percent monosomy and 29.68 percent polysomy), whereas for chromosome 8 this rate was 28.30 percent (6.48 percent monosomy and 21.82 percent polysomy). Statistically significant association (p

The association of the Graves disease (GD) with HLA DR3 and DQA1*0501 in Caucasians has been described previously. From these studies it could not be determined whether one specific locus was primarily involved. Using a case-control study design, we have examined the role of HLA class II gene polymorphisms in the predisposition for GD in a group of Belgian subjects. We demonstrated that both DRB1*0301 and DQA1*0501 alleles conferred significant susceptibility in the DRB1*0301–DQA1*0501 haplotype. The DRB1*0301 allele was the primary susceptibility allele for GD, however, because the susceptibility provided by DQA1*0501 was most likely due to it being in linkage disequilibrium with DRB1*0301. The DRB1*0701/x and DQA1*0201/x genotypes and the DRB1*0701–DQA1*0201 haplotype provided protection with an equal RR of 0.29. Predictive value calculations showed that testing for DRB1*0301 gave the highest positive predictive value for GD in females and males. This was, however, 10 times higher in females and predicted a 3.63% risk for a random female to develop GD. Am. J. Med. Genet. 95:432–437, 2000. © 2000 Wiley-Liss, Inc.

Non-insulin-dependent diabetes mellitus (NIDDM) is a complex disease with a very high degree of heritability. Linkage and segregation analyses have not been very productive in identifying genes responsible for polygenic diseases such as NIDDM, and the majority of the genes determining susceptibility to this disorder remain to be identified. Using a case-control study design, we investigated the possible roles of genes coding for HLA class II antigens, tumor necrosis factor-alpha (TNF-alpha), and immunoglobulin (Ig) allotypes (GM and KM) in a group of Caucasians from Belgium (214 NIDDM patients and 200 controls). All genetic markers were determined by polymerase chain reaction-based methods. We demonstrate that particular homozygous genotypes of TNF-alpha and GM and KM allotypes epistatically interact with HLA-DQalpha1(Arg 52) and contribute to an increased relative risk of NIDDM.