Tehran University Medical Journal

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Background: In the Mediterranean region , Kaposi's sarcoma (KS) has a high prevalence especially in patients with AIDS. Iran is located close to the Mediterranean region and the HIV prevalence is increasing in our country . In some stages, Kaposi's sarcoma is morphologically similar to other vascular tumors. Owing to the presence of human herpesvirus 8 (HHV-8) in all cases of Kaposi's sarcoma , detection of virus DNA by PCR method can help in the identification of non-diagnostic cases. Moreover, the prevalence of HHV-8 genotypes is different in various regions of the world and in different races. There are limited studies performed on the HHV-8 genotypes in Iranian population.

Methods: Patients with Kaposi's sarcoma from 2001 to 2011 who refer to Tehran Razi Hospital were enrolled in this study. HHV-8 DNA was extracted from paraffin blocks and amplification of the virus genome was performed by PCR method . Finally, the target DNA fragment was used for sequencing and genotype determination.

Results: PCR was performed on 53 cases. In 8 cases with suspicious morphology, PCR was negative and they were excluded from study. Of remaining 45 cases, 35 had positive PCR results, 7 had negative results and 3 had low PCR product. Samples from 28 cases that had positive PCR results, which were acceptable for genotyping, were chosen for sequencing. Twenty cases had genotype C, 7 cases had genotype A and one case was negative. The results are consistent with other studies in our geographical area. No correlation was found between the different microscopic stages and HHV-8 Genotypes.

Conclusion: Since the HHV-8 is obtained in almost 100% of KS lesions and PCR s ensitivity in detection of the virus is close to 100 %, KS diagnosis can be confirmed in suspicious cases by detection of HHV-8 DNA on paraffin blocks. Moreover the prevalence of HHV-8 genotype was determined in Iran.

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Background: Bone is one of the most common sites of metastatic disease in malignancies. Many of the cases are asymptomatic and may be diagnosed in primary or secondary follow-up, but in symptomatic cases pain is the prominent symptom which is mostly exaggerated at nights. The improved survival of cancer patients with bony metastases in recent years, specially in breast and prostate cancer, has given a greater importance to the careful choice of treatments in this setting. This can lead to a better quality of life, lower treatment cost, prevention of disabilities, less delay in primary cancer therapies, and decrease of life-threatening events for the patients. Here we review the metastatic disease of the bone and its treatments, with emphasis on local and systemic radiation therapy. Current literature about bone metastasis and its treatments was reviewed through a search of available databases on internet for papers published in 1995-2013. Special attention was given to the research trials and studies performed by the authors on this setting. Treatment of bone metastases consist of analgesics, radiotherapy, surgery and bisphosphonates. Control of bone metastases is a challenging process, necessitating a multi-disciplinary approach and teamwork between the treating physicians. Radiotherapy is the most useful modality for this purpose in oncology, given both as a local and systemic therapy. We hope that this review would be able to help in choosing the best treatment option for this common palliative situation in Iranian cancer patients.

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Background: Rotational deformity after intramedullary nailing is a well-known complication. Femoral malrotation is the most common form of mal::::union:::: but it is underrecognized in part because of the difficulty in accurately assessing rotation as well as the variation that exists in normal anatomy. The aim of this study was to evaluate femoral malrotation following intramedullary nailing of the femur. Methods: We studied 70 patients who had referred to Imam Khomeini Hospital and had undergone antegrade intramedullary fixation for isolated femoral shaft fracture during 3-year period from 2008 to 2011. Inclusion criteria including isolated femoral shaft fracture that had undergone antegrade intramedullary nailing. Exclusion criteria including spontaneous ipsilateral tibial fracture or pelvic fracture, contralateral femoral fracture, femoral fracture that had fixed using plate or external fixator or retrograde intramedullary nailing. During operation, the patients were assessed clinically for rotational deformity and then in the postoperative follow-up period, degree of rotation was identified with CT scan. Postoperative computed tomography measurements of rotation were compared with the opposite side. Results: There were 70 patients, 56 men and 14 women. The average age of the patients was 28.21±14.39 patients (55/7%) had external rotation and 31 patients (44/3%) had internal rotation. The mean of malrotation degree in physical examination was 4/67 and The mean of malrotation degree in CT scan was 7. Degree of malrotation deformity, less of 5º, 5 to 10º and 10 to 15º was less of 8.6%, 75.7% and 15.7% respectively. Degree of malrotation didn’t relate to age, sex, fracture location and activity of the patients (P> 0.05). Conclusion: Rotational deformity in 28% of the patients was equal to more 15º. This complication didn’t relate to fracture location. The patients with external rotation deformity had more symptoms than the patients with internal rotational deformity but there isn’t significant relation in this study.

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Background: The occlusion of the artery and vein grafts are currently a major problem in coronary bypass surgery. Degradation of collagen and elastin, the most abundant extracellular matrix proteins in the vessel wall by matrix metalloproteinase (MMPs), leads to a rearrangement of the extracellular matrix and vascular wall structure. The present study aimed to compare the histological and biochemical characteristics of arteries and veins which could have a role in the failure of the graft. Methods: This study was a cross-sectional study of 80 patients conducted at Heart Hospitals in Isfahan, Iran, between July 2012 and November 2013. Samples were collected from the remains of vessels used in bypass surgery of 11 male nondiabetic patients. The histologic, collagen elastin ratio and MMPs levels of the vessels were investigated. MMPs were determined using the Gelatin Zymography method. For elastin and collagen content measurement, the sample was digested by cyanogen bromide and hydrochloric acid and then hydroxyproline was measured with a spectrophotometer. Results: The amount of active and inactive MMP-2 and MMP-9 of the left internal mammary artery (Lima) was similar to aorta, but the amount of MMP-2 and MMP-9 in the radial artery and saphenous vein were significantly higher than aorta. Elastin to collagen ratio in Lima (1.92±1.15) was similar to the aorta (3.4±1.66), but this proportion in saphenous vein (1.07±0.47) and radial artery (1.14±0.39) was significantly lower in the aorta (P≤0.05). Most patients had atherosclerotic plaque in radial while there was atherosclerotic plaque in Lima of only one case. Conclusion: The presence of atherosclerotic plaques in radial and thickening of the intimal layer of the saphenous vein in the majority of patients and decrease of collagen to elastin ratio and the high level of matrix metalloproteinase enzymes in the radial and saphenous vein can induce early pathological conditions, and remodeling of the vessels involved. So the results of this study confirm that Left Internal Mammary Artery (LIMA) is the most suitable candidate for bypass surgery.

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Pleural effusion (PE) is common among ICU and acutely ill patients. Traditionally plain chest radiography (CXR) has been done for pleural effusion evaluation in ICU. However, better results have been reported by ultrasound for the diagnosis of this condition in ICU. In this study, we compared two methods of ultrasound and CXR in PE detection in ICU patients. Also we studied the percentage of thoracentesis by physician after detection of PE by ultrasonography or CXR. Methods: Portable supine CXR and chest ultrasound were done in Thirty-nine non-surgical patients who were admitted to the Medical and General ICUs of Imam Khomeini hospital in Tehran from Oct 2013 to Mar 2014. Ultrasound was done and interpreted by radiologist and CXR by patient' physician. Thoracentesis or CT-scan was used as gold standard for PE diagnosis. Results: Ultrasound in 29 patients (74.3%) showed PE. In 21 patients thoracentesis was done by patient’s physician and all had PE with mean volume of 447.2(417.6). In 13 of 18 patients without thoracentesis chest CT scan was available. It shows PE in 6 cases (all with positive PE in ultrasonography). CXR in 9 patients (23.1%) was positive for PE and in 30 patients (76.9%) was negative. The ability of chest ultrasound and CXR for diagnosis of PE was significantly different (P= 0.0.1). In 68.9 % of cases that ultrasound was positive, the CXR was negative and only in 34.5% of cases both methods had negative results. The sensitivity, specificity, positive and negative predictive values were 100% (87.1-100), 100% (58.9-100), 100% (87.1-100), 100% (58.9-100) respectively for ultrasonography. For CXR there were 33% (16.6-54.0), 100% (58.9-100), 100% (66.2-100), 28% (12.1-49.4) respectively. Conclusion: Ultrasonography for diagnosis of pleural effusion in ICU patients has better diagnostic performance than portable CXR

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Background: Uterine leiomyoma is one of the most common benign smooth muscle tumors occurring in 20-40% of women worldwide in their reproductive years. Recent studies revealed that estrogen plays an important role in the pathogenesis of this disease. Since glutathione S-transferase (GST) gene family are involved in the biosynthesis of estrogen, the prior probability that variants at this locus are associated with uterine leiomyoma is likely to be above the null. Therefore, this study was carried out to examine whether GSTP1 polymorphism (Ile105Val) is associated with increased risk of uterine leiomyoma in Iranian population. Methods: In this case-control study, 50 women diagnosed with uterine leiomyoma and 50 healthy controls were recruited from subjects referred to the Pasteur Institute of Iran from November 2012 to September 2013. The genomic DNA was extracted from peripheral blood leucocytes using the standard phenol-chloroform method and subsequently the GSTP1 polymorphism was genotyped using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Logistic regression analysis was applied to estimate odds ratios and 95% confidence intervals after age adjustment using the SPSS statistical software package, version 18.0. Results: The results showed significant differences between case and control groups in terms of genotype frequency (P<0.0001). In addition, the results indicated that the presence of the valine allele significantly increased risk of uterine leiomyoma about three times more in individuals carrying the mutant allele compared to control group (Odds Ratio: 3.34 95%CI: 1.82-6.15 P<0.0001). Conclusion: To our knowledge, this is the first study performed in Iranian population assessing the association between GSTP1 Ile105Val polymorphism and risk of uterine leiomyoma. However, further extensive studies with a large number of samples from different populations and ethnicities are required to validate the results obtained in this study.

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Background: Helicobacter pylori vacA (vacuolating toxin A) gene is comprised of mid- (m), intermediate- (i) and signal-regions. Recently, the vacA-i region genotype has been suggested to be a better predictor of disease severity than either the s- or m-region. The main aim of the present study was to determine the associations of i region poly-morphisms of vacA gene with gastric cancer (GC) and peptic ulcer disease (PUD) in Azerbaijan Province patients. Methods: A number of 89 patients were enrolled. The biopsy samples were taken from patients referring to the endoscopy units of Imam Reza and Shahid Madani Hospitals, Tabriz, Iran from August 2012 to May 2013. The genotype frequencies of vacA-i1 and i2 in were studied using polymerase chain reaction (PCR). Results: The frequency of vacA-i1 and i2 was 51.68% and 48.31%, respectively. The genotypic frequency of vacA-i1 in patients with GC (21/24, 87.5%) was significantly higher than in those with non-atrophic gastritis, NAG (19/48, 39.58%). In contrast, the genotypic frequency of vacA-i2 in patients with NAG, PUD, and GC was 60.42%, 64.70%, and 14.28%, respectively. The results of multiple linear and logistic regression analyses confirmed the intensity of correlation of vacA-i1 allele with GC compared with control group (NAG). No significant correlation was found between the vacA-i-region alleles and PUD risk. Conclusion: We have proposed that the H. pylori vacA-i1 genotype could be an im-portant biomarker for predicting the gastric cancer risk in Azerbaijan Province in Iran. However, due to the difference in the allelic frequency of this gene in H. pylori strains from different parts of the world, the vacA-i1 genotype usefulness in predicting the gas-trointestinal diseases is dependent to the geographic origin of the strains.

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Background: Uterine myomas are benign tumors of the uterus and the most common solid pelvic tumors causing symptoms in approximately 25% of women in their reproductive years. However, its etiology and pathogenesis remain obscure there is increasing evidence that endometriosis is inherited as a complex genetic trait. Recent studies indicated the involvement of glutathione S-transferase M1 (GSTM1) gene in the pathogenesis of this disease and current investigations are devoted to the other members of phase II detoxification system genes such as glutathione S-transferase T1 (GSTT1). Therefore, current study was carried out to investigate the distribution of GSTM1 and GSTT1polymorphisms in Iranian population in order to estimate possible impact of null-alleles of each gene in development of this disease. Methods: In this study, 50 patients with endometriosis diagnosed by both pathology and laparoscopic findings according to the revised American Fertility Society classification of endometriosis were recruited from subjects referred to the Pasteur Institute of Iran between November 2012 to September 2013. Accordingly, controls (n=50) were subjects without any of aforementioned gynecologic conditions. The genomic DNA was extracted from peripheral blood leucocytes using the salting out method and GSTM1 and GSTT1 genotyping for gene deletions were carried out using Gap-polymerase chain re-action. Logistic regression analysis was applied to assess whether there was any significant risk increase between the case group with higher null genotypes compared to control group. The level of statistical significance was set at 0.05 and all analyses were conducted using the SPSS version 18.0 (SPSS Inc., Chicago, IL). Results: There was significant evidence that the distribution of the GSTM1 and GSTT1 genotypes differed between the patients and the controls with an allelic odds ratio (OR) of 3.56 (95%CI: 1.35-9.37, P=0.01) and 3.92 (95%CI: 1.4-10 P=0.009) respectively. Data analysis also revealed that individuals with both GSTM1 and GSTT1 null genotypes (-/-) had higher risk to develop the disease in comparison to the people with the both present (+/+) genotype (OR:19.23, P=0.007). Conclusion: The findings suggest that the GSTM1 and GSTT1 genetic polymorphisms are associated with the development of endometriosis in Iranian women which is in agreement with previous results obtained in other populations. However, the ethnic variations of polymorphisms should be evaluated in detail and differences should be incorporated into investigations of susceptibility variants for this disease.

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Background: The major issue to address in endometriosis etiology is to identify the genetic changes in the disease and their occurrence in different populations. Uncovering these genetic changes may be important in developing potential biomarkers for early diagnosis and prognosis of endometriosis. Among all endometriosis susceptibility genes studied before, convincing association has been found with variants in the estrogen receptor alpha (ESR1) gene and this disease however, the contributions of these genetic variants in different populations and ethnic groups are not similar. Accordingly, this study was carried out to replicate the previous findings to assess whether this polymorphism is associated with endometriosis in Iranian women. Methods: A case-control study was designed to determine the possible association between ESR1-351A>G variant and occurrence of endometriosis. The study group consisted of 100 subjects diagnosed with endometriosis as case group and 100 fertile women without endometriosis as controls recruited from subjects referred to the Tehran Women’s General Hospital between January to September 2013. All subjects were genotyped for this marker using amplification refractory mutation system- polymerase chain reaction (ARMS-PCR). Association of risk allele (G) with endometriosis was as-sessed using PLINK software after age adjustment. Results: The results showed that the genotype frequencies were in Hardy-Weinberg Equilibrium (HWE) in both case (F=0.04, P:0.67) and control (F=0.02, P:0.83) groups. In addition, there were no significant differences between case and control groups in terms of genotype frequencies (P=0.17). Moreover, the results indicated that the presence of risk allele (G) did not significantly increase risk of endometriosis (OR: 1.43, 95%CI: 0.96-2.13, P=0.07). Conclusion: The results do not support the previous findings of an association between -351A>G genetic polymorphism in ESR1 gene and endometriosis. Therefore, comprehensive genetic approaches including linkage analyses and family-based tests, together with a number of replication studies with large sample size, are needed to make conclusive claims about the role of this genetic polymorphism in susceptibility to endometriosis.

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Background: Patient-centered care improves the quality of life and health care, and reduces the costs of care. The advent of new technologies such as health social networks, and personal health records (PHR), have significant impact on the patient-centered care. The aim of this article is to analyze and provide a set of features and requirements needed by the users of health social network serving as a PHR (Personal Health Record) system. The combination of capabilities offered by PHRs and social networks providing better delivery of patient-centered care. Methods: In this paper, after a brief study of capabilities and features of existing health social networks and based on a comparative study, a set of requirements which are necessary to create a comprehensive health social network as a PHR system are proposed. Identification of such a systems stakeholders and users e.g. healthcare professionals, patients, and healthcare organizations is important for categorizing the requirements. Also, classifying relatively vast range of existing systems is needed to have a better analyze and design. Results: The proposed health social network can be used by different user groups in healthcare e.g. healthcare professionals, patients, and healthcare organizations. According to the each user group’s requirements, it provides separate facilities for them. The users of this integrated health social network can optionally share some of their information with other users in their group or with users in the other groups and interact with them. Studies show that the proposal requirements and capabilities for health social network not only cover the capabilities of similar systems but also satisfactory provide the requirements of a PHR system to deliver the patient-centered care. Conclusion: The proposed set of requirements are qualitatively compared with the other similar systems. Using the proposed health social network that provides PHR capabilities for its users will have an irrefutable impact on quality and efficiency of patient-centered care, and play an important role in improving the health of society.

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Despite the valuable results achieved in identification of genes and genetic changes associated with type 2 diabetes (T2D), lack of consistency and reproducibility of these results in different populations is one of the challenges lie ahead in introduction of T2D candidate genes. Therefore, the present review article aimed to provide an overview of the most important genes and genetic variations associated with development of T2D based on a systematic search in well-known genetic databases. For this purpose, the National Center for Biotechnology Information, Database of Genotypes and Phenotypes (NCBI dbGaP) and Human Genome Epidemiology Network (HuGENet) database were searched to find the most important genes associated with T2D. In addition, a gray literature search was conducted to collect any available information released by laboratories offering genetic tests such as deCODE genetics and 23andMe. Candidate genes were selected among the results of all databases based on the highest level of similarity. Subsequently, without any time restriction, PubMed, Scopus and Google scholar databases were searched using relevant Medical Subject Headings (MeSH) terms to access related articles. The relevant articles were screened to make a conclusion about the genes and genetic variations associated with T2D. The results revealed that four selected candidate genes, in order of importance, were TCF7L2, CDKAL1, KCNJ11, and FTO. The most significant single nucleotide polymorphism (SNP) associated with T2D in the TCF7L2 gene was rs7903146 however, the results showed a wide range of variation from slight association in the Amish (P= 5.0×10^-2) to strong association in European descent populations (P= 2.0×10^-51). Then, rs10440833 mapping to the intronic region of the CDKAL1 gene showed significant association with T2D (P= 2.0×10^-22). In the KCNJ11 gene, a missense variation (rs5215) in exon one was found to have the highest association with T2D compared with other SNPs discovered in this gene (P= 5.0×10^-11). Finally, rs8050136 located in the first intron of the FTO gene had the strongest association with T2D (P= 2.0×10^-17). On the basis of these results, it can be concluded that the current study can be introduced as a model for achieving well-documented results among spectrum of information available in genetic databases based on a systematic search strategy. The candidate genes and genetic variations presented in this review article might be applied for early diagnosis, prevention, and treatment of T2D.

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HIV/AIDS is among the leading causes of morbidity and mortality in world. There are more than 35 million people living with HIV/AIDS in the world. Although the annual incidence of HIV infection is decreasing globally, HIV prevalence is rising due to development of more effective treatment and higher survival. Iran suffers from concentrated HIV epidemics among injecting and non-injecting drug users. There are more than 27 thousand registered cases of HIV infection and it is estimated that there are above seventy eight thousand cases in the country. Regarding the burden of disease, it is projected that HIV/AIDS will have the highest growth during the next 10 years. The outcome of this epidemics will be determined by human behavior. HIV, psychiatric disorders and substance use disorders are closely correlated and are accompanied by similar risk factors. They also share common consequences such as stigma and discrimination. Correlation of psychiatric disorders, as one of the most influential determinants of our behavior, and HIV/AIDS infection is reviewed in this narrative article. Psychiatric disorders are associated with greater risk of HIV acquisition. Substance use disorders, both injecting and non-injecting, as well as severe mental illnesses put the individual at higher risk of acquiring HIV infection. Impaired judgment, diminished inhibition and control over behaviors, lack of insight and poor self-care have been proposed as the underlying mechanisms. On the other hand, HIV infection may put the individual at greater risk of developing a mental illness. Coping with a chronic and life-threatening illness, fear of stigma and discrimination, CNS invasion of the virus as well as the adverse neuropsychiatric side effects of anti-retroviral medications may all contribute to establishment of a psychiatric disorder. Although there exists a bi-directional correlation between mental health problems and HIV/AIDS infection, this reciprocity goes beyond. Psychiatric disorders can affect the patient’s adherence, access to treatment and care and can worsen the course and clinical outcome of the infection. The clinical importance, underlying mechanism and other implications of this correlation are reviewed in this article.

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Background: This study investigated compatibility between post chemoradiation magnetic resonance images and histologic findings after operation and chemoradiation in patients with locally advanced rectal cancer.

Methods: In this prospective study, 63 patients referred to Cancer Institute of Emam Khomeini Hospital, Tehran, Iran, from October 2011 to October 2013 with locally advanced rectal cancer receiving neoadjuvant chemoradiation (50.4 Gy external beam radiation with concomitant capecitabine 825 mg/m2 PO twice a day with or without 60 mg/m2 oxaliplatin weekly). Patients had an MRI before chemoradiation and MRI assessment were used to identify Tumor (T) and lymph node (N) staging by an experienced radiologist. Patients were recommended to repeat MRI after surgery but it was not obligatory. Findings of post chemoradiation MRI and histopathologic reports were compared. Downstaging was defined as at least one stage decrease in T or N in histopathologic report comparing to their first MRI, on condition of no sign of disease progression.

Results: 32 patients (50.79%) had T downstaging and 36 of them (57.14%) showed N downstaging: none had disease progression. In this study MRI had an accuracy of 55.5% for rectal tumor (T) restaging after chemoradiation comparing to pathology. MRI sensitivity for T restaging was 33.3% to 83.3%.  There was a higher possibility to have errors in restaging of T1-2 stages. Specificity of MRI for T restaging was higher than its sensitivity, 66.6%. In this study lymph node involvement (N) was determined according to morphology and size. MRI has an accuracy of 42.8% for detecting lymph node involvement. Its sensitivity and specificity for N restaging were 50% and 66.6% respectively. All patients had MRI before chemoradiation, although 21 of them repeated MRI after chemoradiation since it was not mandatory. 19 of these 21 patients underwent surgery.

Conclusion: Although MRI is a suitable imaging for staging locally advanced rectal cancer its use for restaging after chemoradiation is under question. According to this study, MRI accuracy rates for both T and N restaging were below the rates of previous studies.

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Background: Over the last two decades invasive candidiasis has become an increasing problem in neonatal intensive care units (NICUs). Colonization of skin and mucous membranes with Candida spp. is important factor in the pathogenesis of neonatal infection and several colonized sites are major risk factors evoking higher frequencies of progression to invasive candidiasis. The aim of this study was to detect Candida colonization in NICU patients.

Methods: This cross-sectional study was conducted on 93 neonates in NICUs at Imam Khomeini and Children Medical Center Hospitals in Tehran. Cutaneous and mucous membrane samples obtained at first, third, and seventh days of patients’ stay in NICUs during nine months from August 2013 to May 2014. The samples were primarily cultured on CHROMagar Candida medium. The cultured media were incubated at 35°C for 48h and evaluated based on colony color produced on CHROMagar Candida. In addition, isolated colonies were cultured on Corn Meal Agar medium supplemented with tween 80 for identification of Candida spp. based on their morphology. Finally, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was performed for definite identification of isolated species.

Results: Colonization by Candida spp. was occurred in 20.43% of neonates. Fifteen and four patients colonized with one and two different Candida spp., respectively. Isolated Candida spp. identified as; C. parapsilosis (n: 10), C. albicans (n: 7), C. tropicalis (n: 3), C. guilliermondii (n: 2), and C. krusei (n: 1). In present study non-albicans Candia species were dominant (69.56%) and C. parapsilosis was the most frequent isolate (43.47%). Using Fisher's exact test, the correlation between fungal colonization with low birth weight, low gestational age, and duration of hospital stay was found to be statistically significant (P=0.003).

Conclusion: The results of this study imply to the candida species colonization of neonates. Neonates in NICU are at the highest risk for severe infection with Candida parapsilosis. Therefore, isolation of C. parapsilosis as the most common species (43.47%) in present study was noteworthy.

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Background: Data mining is known as a process of discovering and analysing large amounts of data in order to find meaningful rules and trends. In healthcare, data mining offers numerous opportunities to study the unknown patterns in a data set. These patterns can be used to diagnosis, prognosis and treatment of patients by physicians. The main objective of this study was to predict the level of serum ferritin in women with anemia and to specify the basic predictive factors of iron deficiency anemia using data mining techniques.

Methods: In this research 690 patients and 22 variables have been studied in women population with anemia. These data include 11 laboratories and 11 clinical variables of patients related to the patients who have referred to the laboratory of Imam Hossein and Shohada-E- Haft Tir hospitals from April 2013 to April 2014. Decision tree technique has been used to build the model.

Results: The accuracy of the decision tree with all the variables is 75%. Different combinations of variables were examined in order to determine the best model to predict. Regarding the optimum obtained model of the decision tree, the RBC, MCH, MCHC, gastrointestinal cancer and gastrointestinal ulcer were identified as the most important predictive factors. The results indicate if the values of MCV, MCHC and MCH variables are normal and the value of RBC variable is lower than normal limitation, it is diagnosed that the patient is likely 90% iron deficiency anemia.

Conclusion: Regarding the simplicity and the low cost of the complete blood count examination, the model of decision tree was taken into consideration to diagnose iron deficiency anemia in patients. Also the impact of new factors such as gastrointestinal hemorrhoids, gastrointestinal surgeries, different gastrointestinal diseases and gastrointestinal ulcers are considered in this paper while the previous studies have been limited only to assess laboratory variables. The rules of the decision tree model can improve the process of diagnosing and treatment of the patients with iron deficiency anemia and reduce their costs.

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Background: Metformin has been suggested as anti-cancer in retrospective studies. We design a prospective controlled study about metformin efficacy in the window time between biopsy and definite surgery with changes of Ki-67 as the primary endpoint.

Methods: The primary cohort had composed of 50 pathologically diagnosed invasive breast cancers, accrued in Medical Oncology Department of Iran Cancer Institute from February to November 2014. Patients neither had indication of neoadjuvant chemotherapy, nor involved with diabetes mellitus. They followed during the time period of biopsy and definitive surgery with taking tests on pathology specimens for ER, PgR, HER-2/neu and Ki-67 index. We checked fasting insulin and glucose level as well as quality of life and adverse effects in both times in the intervention group. Metformin (1500 mg/day) was prescribed to intervention group from pathology report to the night before surgery.

Results: From 45 patients, 25 had been received metformin for median time of 2.8 weeks. Controlled group included 20 patients who followed in the window time. There were no statistically significant differences between two groups regarding baseline clinical and tumor characteristics such as age, stage, grade, ER, PgR, HER2 status, time and type of surgery. However, immunohistochemistry study showed decrease of median Ki-67 from 35.14 to 29.6% in the intervention group and increase from 24.5 to 30.6 in the control group. Both of these results were statistically significant. Patients tolerated metformin very well, but mild gastrointestinal symptoms were seen in 30% of cases. There was a correlation between metabolic factor of HOMA score (fasting insulin level fasting blood sugar/405) and changes in Ki-67.

Conclusion: In the present study metformin prescription in the short period of time between Biopsy and definite surgery had shown inhibition of breast cancer cell growth. We found relationship between metformin anti-proliferative effect and glucose and insulin metabolism. To find direct apoptotic stimulation of metformin and long-term results of this drug further studies in the adjuvant settings with cooperation of pharmacokinetic groups are recommended.

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Background: Cervical cancer is known to be preventable because of long period of pre-invasive stage, availability of screening tools, and effective treatments for early invasive cervical lesions. Screening is main measures to prevent the disease and Pap smear is a screening strategy for cervical cancer. Current paper aimed to evaluate levels of awareness and practice regarding Pap smear screening among women aged between 20 to 65 years in Tehran (Iran). Methods: This was a descriptive-analytical study conducted in Tehran City of Iran in 2015 at Firoozgar Hospital. The research population included all married, widowed and divorced women aged 20-65 years. Data analysis was performed using the Pearson correlation and Student’s t-tests in SPSS, ver. 23 (Chicago, IL, USA). Results: Among 90 individuals who have fill questionnaire completely, 66.6% subjects had Pap smear tests. 40% of the individuals aged between 30 to 39 and the education level is distributed equally between Intermediate, Diploma and graduate and only 3 percent of them, continue their education to higher level. There was a significant relationship between the awareness of Pap smear and educational level (of both wives and husbands). The people who have graduate degree, have the best awareness. Working women revealed higher level of awareness about Pap smear. Shame and fear of taking the cancer were the most common reasons which lead to avoidance in doing the test by the women, while the most encouraging factors for performing the test were the information mostly provided by physicians and after that, the information provided by friends. Conclusion: The awareness of Pap smear test which was measured by weighting different questions in the questionnaire by experts, prove that the women aged above 39, have an average level of awareness of Pap smear test. Due to high prevalence of cervical cancer and prolonged pre invasive course, role of Pap smear for early diagnosis necessitate the use of proper and inexpensive instructional methods to increase awareness in women about cervical cancer and preventive strategies.

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Clostridium difficile (C. difficile) is an important factor in the development of the gastrointestinal diseases because of irrational antibiotic prescription and antimicrobial resistance. In the past, this bacterium was introduced as an agent of the infection in the hospitals called "hospital acquired Clostridium difficile infection". This infection is a main cause of morbidity and mortality internationally. But changing in the epidemiology of the infection was observed in recent years. People not taking antibiotics as well as any contact with the clinical system were hospitalized due to the infection named "Community-Associated Clostridium difficile infection". Furthermore, the hypervirulent strains of C. difficile were identified outside of the health care facilities in different sources such as environment, animals and food products. Today the role of C. difficile has not been confirmed as a zoonotic agent or foodborne pathogen. Taking into account, it should be taken attention to the sensitive individuals such as pregnant women, elderly and children for the consumption of the contaminated food products with C. difficile spores and probable cause of the infection in these individuals. For this purpose, presentation of the guidelines or the prevention strategies for the transmission of bacteria in the society as well as the healthcare facilities is important. In this review study, the history, the risk factors of disease and the reports of infection in the healthcare facilities and outside of this environment in Iran were discussed. Finally, we supposed that based on the isolation of C. difficile with different genetic profile in Iran in comparison with international ribotypes, the existence of native strains leading to the infection in the community and the healthcare facilities is possible. This hypothesis shows the significance of regional differences in the epidemiology and microbiology of disease. In addition, according to the present reports on the irrational prescription of the antibiotics in our country, it seems that C. difficile infection is increasing but any continuous monitoring is not being occurred for the supervision in Iran. Approving these hypotheses need to the careful and continuous assessment besides comprehensive examination of molecular epidemiology of disease in the organizations related to the health in Iran.

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Background: Multiple sclerosis (MS) is a chronic inflammatory disorder of the CNS characterized by destruction of the myelin sheath, gliosis and progressive neurological dysfunction. The regulatory T (Treg) cells play a major role in the control of the autoimmunity and inflammation. The forkhead box p3 (FOXP3) is a central molecule in the function of Treg cells that play an important role in the immunoregulation. The aim of this study was to investigation single nucleotide polymorphism (SNP), rs2232365, in FOXP3 gene in patients with multiple sclerosis.

Methods: In a case-control study, peripheral blood samples were collected from 90 patients with MS (46 men and 94 women with different patterns of disease) from January 2014 to April 2015 in the Afzalipoor Hospital, Kerman (a city located in the southeast of Iran). In a total, 90 healthy subjects were also enrolled into the investigation as a control group. The healthy subjects were recruited among blood donations of the Kerman Transfusion Organization and interviewed regarding CNS disease, and none of them had any history of CNS diseases or other relevant disorders. The SNP rs2232365 in FOXP3 gene was assessed by single specific primer-polymerase chain reaction (SSP-PCR) method. Finally, statistical analysis was performed using SPSS version 22 (Chicago, IL, USA).

Results: In both patients and healthy control groups, there was significant difference among subjects with GG, AG, and AA genotypes at rs2232365 in FOXP3 gene. The frequencies of AA and AG genotypes at rs2232365 in the FOXP3 gene were significantly higher in MS group as compared with healthy subjects (P<0.002). Moreover, the frequency of GG genotype was significantly lower in the MS group in comparison with healthy control subjects (P<0.002). The frequency of A allele was significantly higher whereas the frequency of G allele was significantly lower in MS patients as compared with healthy subjects (P<0.001).

Conclusion: The results of the present study suggest that SNP rs2232365 may influence the susceptibility to multiple sclerosis. Therefore, SNP rs3761548 may directly or indirectly alter the level of the FOXP3 protein expression in Treg cells.

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Background: As far as the role and amount of Transferrin receptor 2 (TFR2), which is the transferrin receptor gene, studies have been conducted, some of which confirming its relationship with gastric adenocarcinoma. The idea behind this study was to examine changes in the TFR2 gene expression in the tumor cells of gastric adenocarcinoma and comparing with gene expression in the normal tissue adjoining the tumor.

Methods: This case-control study was conducted at the Pathology Section of Cancer Institute of Imam Khomeini University Hospital in Tehran from September 2015 to September 2016. In this study, 30 fresh samples from tumor tissues of patients diagnosed with gastric adenocarcinoma, 30 fresh samples of normal tissue adjoining the tumor and 30 samples of frozen plasma from the same patients were taken. The patients' plasma was examined in terms of existence of helicobacter pylori antibody by enzyme linked immunosorbent assays (ELISA) method and TFR2 gene expression in the tumor tissue and the adjoining normal tissue by applying real-time polymerase chain reaction (Real-Time PCR).

Results: Gene expression (by applying real time polymerase chain reaction) in the tumor tissue was meaningfully higher than in the normal tissue (P= 0.125). The TFR2 expression in patients with stomach cancer, who were at the same time infected with helicobacter pylori, indicated that the gene expression had increased in those with this contamination (P= 0.077). Examining the relationship between this gene expression and the stage of disease showed that the TFR2 gene expression increased significantly in the more advanced stages of the disease (P= 0.396).

Conclusion: The TFR2 gene expression increases in the stomach's tumor tissue. This gene expression is higher in people infected with helicobacter pylori or in those at an advanced stage of the disease. These findings may confirm the direct relationship between gene expression and the occurrence or metastasis of gastric adenocarcinoma.