Tehran University Medical Journal

Background: Each year, Human influenza A (H1N1) virus causes moderate to severe infections with a high prevalence throughout the world. Accordingly, the rapid, sensitive and cost-effective laboratory diagnosis based on viral antigen detection is important. Moreover, the generation of specific antibodies directed against Influenza antigens is essential to the success of both basic and applied research programs. Hemagglutinin (HA) is the major surface envelope glycoprotein of influenza virus, which is subsequently cleaved into two subunits, HA1 and HA2. Since most antigenic sites are in the HA1 domain of HA, HA1 domain of influenza virus was studied as antigen to produce polyclonal antibody.
Methods: In this experimental study we expressed and purified the recombinant HA1 protein in the second half of 2015 at department of influenza and other respiratory viruses, Pasteur Institute of Iran and then prepared the polyclonal rabbit antibody against it. The vector of pET28aHA1 expressing HA1-His tagged protein of H1N1 influenza A/PR/8/34 virus was used for large scale production of HA1 into E. Coli (BL21). By changing expression conditions such as IPTG (Isopropyl β-D-1-thiogalactopyranoside) concentration, time and temperature of incubation, the expression conditions for HA1 were optimized. The total cell protein harvested and purified by nickel affinity chromatography. All above mentioned experiments monitored by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE).
Results: The efficiency of HA1 recombinant protein was high, equal to 400-600 mg/ml of cell lysate. The polyclonal antibody was prepared by immunizing the rabbits using recombinant HA1 with Freund’s adjuvant according to standard protocols. Efficiency of the antiserum evaluated by enzyme linked immunosorbent assay (ELISA). Determination of antibody level in the collected antiserum using serum-based ELISA showed that the specific antibody has risen well through the immunization schedule.
Conclusion: Our data shows that this polyclonal antibody has potential to be produced in rabbit. It will also be used in the future in influenza diagnosis as well as in other immunological applications such as western blot analyses, immunocytochemistry, and immunohistochemistry.
 

Background: According to the direct connection between congenital hypothyroidism and iodine deficiency in pregnant women, also relatively high incidence of congenital hypothyroidism in some areas of Kerman province, especially Raver district located in North of Kerman province, this study was performed to determine and compare the urinary iodine concentration (UIC) in pregnant women referring to health centers.
Methods: This cross-sectional study was done during March 2014 and May 2015. Inclusion and exclusion criteria to be considered and UIC were measured by spectrophotometry in 384 and 374 pregnant women in Ravar and Kerman cities, Iran. Sampling method for this study was all of pregnant women in Ravar and random stratified sampling in Kerman. data were collected using a structured questionnaire. All statistical analyses were performed using SPSS Software, version 20.0 (IBM SPSS, Armonk, NY, USA). Chi-square test, Pearson's correlation coefficient and Logistic regression were used for associations and differences.
Results: The mean UIC was 200.21 µg/L in pregnant women of Ravar and 238.79 µg/L in pregnant women of Kerman. 22.7% of pregnant women were with low concentrations of iodine, 57.8% within the normal range and 19.5 percent were with high iodine concentrations in Ravar. While 5.3 percent of pregnant women were with low concentrations of iodine, 54.5% were within the normal range and 40.1% were with high UIC in Kerman. There were no significant differences between demographic variables and UIC in the two regions (P> 05/0). Multivariate regression models showed significant connections between the residence and UIC pregnant women (P< 0.001).
Conclusion: The results of this study showed that UIC in pregnant women of Ravar was significantly lower than Kerman and the place of living can be considered as a predictor of UIC in pregnant women.

Background: Gastric cancer is among the most common malignancies in certain parts of the world, such as northwest Iran. miRNAs are small and single-stranded noncoding RNAs with about 19-23 nucleotides. Several studies have shown that miRNAs play important roles in gastric tumorigenesis. The aim of this study was to determine the effect of miRNA-1266-5p repression on the cell survival and alterations of the cell cycle in gastric cancer cell line of AGS (NCBI Code: C131, Gastric epithelial cell line).
Methods: This experimental study was performed from April to December 2017 in Cellular-Molecular Research Center of Ardabil University of Medical Sciences, Iran. In this study, AGS cells were cultured in RPMI-1640 medium containing 10% serum and 1% antibiotic. The cells were transfected with miR-1266-5p mimic, miR-1266-5p inhibitor and HiPerFect reagent alone as negative control. The miR-1266-5p expression and transfection efficiency were analyzed by Stem-loop TaqMan qRT-PCR. The cell proliferation and cell cycle alterations were determined using MTT calorimetric assay and flow cytometry, respectively. The results were analyzed using SPSS 19.0 statistics software (SPSS Inc., Chicago, IL, USA) and presented as the means±standard deviation (SD).
Results: miR-1266-5p expression was increased in AGS cells transfected with miR-1266-5p mimic compared to control cells (P=0), while miR-1266-5p expression was decreased in transfected cells with the inhibitor compared to controls (P=0). Among different time points, the most effects of miR-1266-5p mimic and inhibitor were noticed after 48 hours of transfection. The upregulated miR-1266-5p significantly decreased cell growth, in contrast, inhibitor promoted cell proliferation (P=0). In addition, miR-1266-5p upregulation induced cell cycle arrest at the transition of G1 to S phase and led to G0/G1 entry (P=0), while of miR-1266-5p led to G2/M entry (P=0.001).
Conclusion: According to the results obtained from this study, miR-1266-5p can reduce cell survival and induce cell cycle arrest and act as a tumor suppressor in AGS cells. While its inhibition can increase cell survival and reduce apoptosis.

Anaplasma phagocytophilum is a gram-negative intracellular bacterium that transmitted by hard ticks. A. phagocytophilum infect and multiply in the organs of ticks, in particular the salivary glands which enable the transmission to vertebrate hosts during feeding. The tick becomes infected by feeding on an infected host and there is transstadial but not transovarial passage of the organism. The majority of ticks are infected with the organism in enzootic areas. There are strains of A. phagocytophilum that have biological and ecological difference, including variations in host pathogenicity, vectors and geographical distribution. The organism has an interesting feature to grow in neutrophils by stopping the antibacterial activity of neutrophils. The bacterium is able to survive in the immune host, using complex mechanisms of antigenic variation. A. phagocytophilum infects humans and various animal species including dogs, sheep, cows, horses, wild deer and rodents. The disease is known as human granulocytic anaplasmosis in humans, canine granulocytic anaplasmosis in dogs, equine granulocytic anaplasmosis in horse and tick borne fever in ruminants. Cattle tick borne fever caused by A. phagocytophilum is characterized by high fever, reduced milk yield, inclusions in circulating neutrophils, leukopenia, abortions, reduced fertility, coughing, respiratory signs and swelling of the hind limbs. Clinical signs of human occur a week after the tick bites, the disease usually presents as an acute, sometimes fatal febrile syndrome, illness characterized by headache, chills, myalgias, arthralgia, malaise, and hematological abnormalities, such as neutropenia, lymphocytopenia, thrombocytopenia, leukopenia, and elevated hepatic aminotransferase levels and may lead to death. In this review article the history, bacteriology, epidemiology, pathogenesis, diagnosis, treatment and prevention of the disease caused by A. phagocytophilum is written based on the latest scientific findings. Several hard tick species are distributed in Iran and they are the most important ectoparasites of animals. A. phagocytophilum has been detected not only in Ixodes ricinus but also in cattle and sheep of Iran using molecular techniques. However, despite the zoonotic potential of the agent, there is no evidence in the identification of A. phagocytophilum in humans, and it seems necessary to research on the prevalence and epidemiology of the disease in the human population.

Background: Nutrition education and introduction of procedures for choosing healthier food have an important role to reduce the rate of non-communicable diseases. It was shown the amount of risk factors of non-communicable diseases such as energy, salt, sugar, fat and trans fatty acid on the traffic light of food labelling. The status of risk is presented through three colors of red, yellow and green that are the signs of risk, precautious and safe use of food. The object of this study was to evaluate the influence of education on the knowledge, attitude and practices of Isfahan University of Medical Sciences students to the traffic light on food labeling.
Methods: This project was an empirical study performed by random sampling of 379 students of nine schools in Isfahan University of Medical Sciences from January 2017 to March 2018. The knowledge, attitude and practices of students toward the traffic light were assessed by self-administered and structured questionnaire. Education was performed face to face with the usage of pamphlet. In the period of three to six months, questionnaires were refilled out by students to determine knowledge, attitude and practice. Descriptive statistics were calculated using SPSS in mean± SD. Paired t-test was performed to assess the influence of education in total score of knowledge, attitudes and practices in test-retest. P value was considered less than 0.05 as statistically significant.
Results: Before education, the average of scores for knowledge, attitude and practice was 1.12±0.84, 14.44±4 and 2.25±2.2, respectively. Afterwards, the scores were increased to 11.72±0.75, 18.67±3.18 and 17.69±4.7 after education. Significant difference was observed in the scores of knowledge, attitude and practice of students before and after education (P<0.05).
Conclusion: Education of traffic light had a significant role in the improvement of knowledge, attitude and to some extent of practice of students in selection of healthier food.

Background: Cerebral aneurysm disease causes intracranial hemorrhage by rupturing, which can eventually, lead to organ failure or death. For this reason, it is important to anticipate the reasons for rupturing of a cerebral aneurysm from biomechanical point of view. Investigating this disease may even help the physicians to find treatments and predict the patient’s situation. This research was conducted to understand risks of development and rupture of a patient-specific cerebral aneurysm.
Methods: In a computational simulation, fluid-structure interaction method has been used for a patient-specific case. Also, considering the speed of the systole as the initial condition of the problem, the blood fluid domain has been solved in three types of fluid mathematical models (Newtonian, non-Newtonian Carreau, and non-Newtonian power-law). Then, the pressure results on the wall have been transmitted to ANSYS software, version 15.0 (ANSYS Inc., Canonsburg, PA, USA) and the structure has been solved based on three material models (linear elastic, hyperplastic Neo-Hookean and hyperplastic Mooney-Rivlin, with 5 parameters). The study was done in University of Tehran, Iran, from October 2016 to September 2018.
Results: Shear stress, pressure, flow velocity, wall displacement and von-Mises stress have been extracted from the simulations. The average wall displacement of the aneurysm was 1.8 mm. Also, no significant difference was found in the amount of arterial wall displacement, with constant wall material model and different blood models. However, a significant difference has been observed in the case of considering constant blood model and different wall material models in the value of displacement.
Conclusion: With regard to the amount of displacement of the aneurysm wall in this particular patient, with the geometry and location of the specific aneurysm, the brain nerves 3 and 6 were under stress and exposed to damage. The minimum shear stress was in the aneurysm neck, which stimulates the endothelial cells in the area of aneurysm. In addition, the blood model didn’t had a significant effect on the displacement calculations, while the wall material model played a more decisive role.

Background: Clopidogrel is an effective anti-platelet drug that is commonly prescribed for patients with atherosclerotic coronary and peripheral vascular diseases, especially after angioplasty and coronary artery bypass graft surgery. Even though this drug seems safe, there are case reports of important side effects with its use.
Case Presentation: The patient was 67 years old male admitted with a diagnosis of inferior myocardial infarction who underwent angioplasty on RCA with a drug-eluting stent and was discharged with an uneventful course from hospital with medical treatment, including Clopidogrel. The patient came back to the clinic 30 days later with icter, nausea and loss of appetite. The lab data showed: Bilirubin (total= 5, direct=4), ALT=220, AST=100, Gama GT=830, Alk.phop=445. Virologic and imaging studies were normal. With a possible diagnosis of drug-induced hepatic injury all possible Prescribed drugs were held stepwise but bilirubin and the patient’s symptoms did not relieve until Clopidogrel has been changed. After 10 days bilirubin and his symptom relieved.

Background: Asthma is the most prevalent chronic disease in childhood and has been growing globally over the last three decades. Studies in this regard indicate different and irrelevant results in Iran. Different prevalence of asthma has been reported in industrialized countries, prevalence of 25.9% in the United Kingdom, 12.8% in Spain and 31% in Australia. This study aimed to evaluate asthma in Iranian children through systematic review and meta-analysis.
Methods: This study was performed as a systematic review and meta-analysis from January 2001 to December 2018. Related articles to the reviewed subject were obtained through searches of Scopus, ScienceDirect, Magiran, SID, Medline (PubMed), and Google Scholar databases. Cross-sectional studies were selected for inclusion in the study and observational studies as well as review studies were excluded from the study. Searches on Google search engine and the inspection of sites related to the topic were also incorporated to examine the grays literature. Duplicate articles and articles that were similar and obtained from the same source were removed through the EndNote software. The total number of articles was 896. Subsequently, the number of articles and studies that met the requirements of the first stage was 274. Ultimately after the elimination of 236 irrelevant articles and the elimination of 5 articles in the secondary examination, eventually 33 articles were added to the final stage. By the I² index, the heterogeneity of the studies was investigated and reported.

Background: Cholangiocarcinoma is a cancer of the bile duct epithelium that originates from the bile ducts inside or outside the liver. Although this tumor is not common, its mortality rate is high. This tumor accounts for about 3% of all gastrointestinal malignancies. Many patients are being detected when the disease has spread. Evaluating risk factors affecting the incidence of cholangiocarcinoma is very important to avoid exposure to them. Therefore, this study was performed to evaluate the risk factors for cholangiocarcinoma in a population in Iran.
Methods: This was a descriptive cross-sectional study. It was performed on 276 patients with cholangiocarcinoma who had been referred to Firoozgar Hospital affiliated with the Iran University of Medical Sciences in Tehran from March 2020 to February 2021. Demographic information, family and personal history, social history (tobacco or drug use) and blood group of patients were extracted from their files. SPSS version 16 was used for data analysis. A P-value below 0.05 was considered statistically significant.

Background: Healing involves complex processes that are not yet fully known. The wound healing process consists of three stages. In all these stages, normal wound healing requires platelet activation, release of cytokines and growth hormones, and chemotaxis and cell differentiation. Platelets play a key role in homeostasis and wound healing and growth factor production of more than 30 carried out by them. Platelets regulate the healing process with their chemotactic effect. Antilogous PRP platelet count in about 3 to 5 times increase and consequently also increases the number of growth factors, for this reason, they are being used in surgical procedures and clinical therapy.
Methods: At Ilam Medical Center in Imam Khomeini Hospital, 20 patients with two similar donor graft sites were gradually selected to participate in a clinical trial from January to March 2017. The two regions have the same skin graft patients, an area of Honor conventional and other areas with the topical administration of platelet-rich plasma That immediately after surgery and in the days after the fifth and eleventh, eightieth and after washing the wound with a topical serum Physiology rubbed on the wound and thus treated The rate of wound healing clinically and using X-ray photo-checked and compared.

Background: The clinical field has vast sick data that has not been analyzed. Discovering a way to analyze this raw data and turn it into an information treasure can save many lives. Using data mining methods is an efficient way to analyze this large amount of raw data. It can predict the future with accurate knowledge of the past, providing new insights into disease diagnosis and prevention. Several data mining methods exist but finding a suitable one is very important. Today, coronavirus disease (COVID-19) has become one of the causing deadly diseases in the world. The early diagnosis of pandemic coronavirus disease has a significant impact in preventing death. This study aims to extract the key indications of the disease and find the best data mining methods that enhance the accuracy of coronavirus disease diagnosis.
Methods: In this study, to obtain high accuracy in diagnosing COVID-19 disease, a complete and effective workflow over data mining methods was proposed, which includes these steps: data pre-analyzing, indication selection, model creation, the measure of performance, and display of results. Data and related indications of patients with COVID-19 were collected from Kerman Afzalipour Hospital and Rafsanjan, Ali Ebn Abi Taleb Hospital. Prediction structures were made and tested via different combinations of the disease indications and seven data mining methods. To discover the best key indications, three criteria including accuracy, validation and F-value were applied and to discover the best data mining methods, accuracy and validation criteria were considered. For each data mining method, the criteria were measured independently and all results were reported for analysis. Finally, the best key indications and data mining methods that can diagnose COVID-19 disease with high accuracy were extracted.

Results: No RBC was detected in microscopy. The majority of the leucocytes were lymphocytes with rare accompanying platelets. The radiolabeling efficiency of the procedure was higher than 40%. The viability test indicated more than 80% of viable cells. The radiochemical purity of the final product was more than 95%. Two to four hours after injection, low background images were acquired. The liver and spleen were target organs with low-grade urinary, thyroid, and GI activity. Conclusion: Employing multi-stage centrifugation, Tc-HMPAO labeled leucocyte scan could be efficiently performed.

Background: Since numerous chemotherapy regimens for the treatment of patients suffering from acute lymphoid leukemia (ALL) have been recently developed, having basic information about the previous results of using the Hyper-CVAD regimen in order to compare with other common chemotherapy regimens is essential. The aim of this study was to evaluate demographic, clinical and outcome of ALL patients receiving Hyper-CVAD regimen.
Methods: In this retrospective study, nighty eligible ALL patients treated with the Hyper-CVAD chemotherapy regimen in Omid Hospital, Isfahan, Iran during April 2016 till April 2019 were considered. We evaluated the demographic variables, pathological data and other clinical factors by an information sheet designed by main investigator. The main purpose of this study was to evaluate overall survival, progression-free survival, and overall response rate of patients along with patients’ clinical characteristics and other relevant factors using Kaplan-Meier or Cox-regression and other statistical analyses. 

Results: The mean overall survival and the median survival of patients were 44.8±2.93 and 36.7±7.47 months; respectively. Also the mean progression free survival of patients was 44.44±3.30 months. More than 84.4% of patients encountered complete remission (CR) after receiving Hyper-CVAD regimen. Reaching to CR had positive significant effects on patients’ overall survival and median survival. However, the bone marrow transplantation variable alone did not affect the patients’ overall survival. The variables such as being B/T Cell ALL, Philadelphia, myeloid marker, and central nervous system involvement did not affect the overall survival of patients but the relapse index indicated the significant effects. The median survival time is higher in patients with no relapse episode. None of the initial lab data had any significant effects on patients’ overall survival. Conclusion: For the first time in Iran, we have obtained the mean survival outcome of ALL patients after applying the Hyper-CVAD regimen. According to the results, the mean overall survival, progression free survival and other survival items in Iranian patients suffering from ALL and receiving Hyper-CVAD regimen were in consistent with previous studies in the world.

Background: According to numerous research related to learning styles and also the difference of these styles in students, this study was designed in order to determine the status of learning styles in medical students in Iran.
Methods: This study was conducted as a systematic review and meta-analysis. Searching for articles in this study was done from September 24 to October 15, 2022 in databases: Proquest, PubMed, Iran medex, Scopus, Sid, Magiran, Google Scholar, Eric and medical education journals. The research environment of Iran has been Mashhad. Using the PICOTS model, the keywords: learning styles, clubs, medical students were used to search the mentioned databases. OR, AND operators and possible combinations of keywords were used when searching for articles in databases. The extracted articles were first evaluated in terms of the research title, then the abstract of the article, and finally the text of the article using the "PRISMA Checklist". In each stage, repetitive articles and articles that did not mention the percentage of learning styles were excluded from the study, and the articles that met the inclusion criteria were stored in the (EndNote software, version 20, Clarivate, USA), and at the end, 53 articles were analyzed.

Results: The results of the study showed that the most used learning styles among students of medical sciences in Iran was convergent learning style (32% with 95% confidence interval). In the investigation of the adaptive learning style in the fields of basic sciences during the years 2006 to 2021, the percentage of using this style increased and this trend was statistically significant (P=0.0078). Conclusion: According to the findings of the study, the most used learning style in medical sciences in Iran is convergent learning style, and considering the characteristics of convergent people, it is necessary to provide effective and efficient training in medical sciences to Students' learning styles should be given special attention so that training can be guided based on their learning styles.

Background: Due to the fact that various factors are involved in the development of chronic kidney disease, this disease appears with different clinical and laboratory symptoms. The variety in type and number of clinical symptoms often misguides the treating physician. The aim of this study is to extract the key features of the disease and find the best data mining methods to improve the accuracy of kidney disease diagnosis.
Methods: This cross-sectional study was conducted from September 2021 to March 2023 for 30 months at Rafsanjan Ali Ebn Abi Taleb Hospital. Predictive models were developed and tested using different combinations of disease characteristics and seven data mining methods in RapidMiner Studio software. The limitations of the study are as follows: 1) The models were based on 40-year-old and older patients records, which may limit the generalization of results to a wider age group. 2) Despite the high accuracy and comprehensiveness of the method, the models were based only on the information of kidney disease patients at Ali Ibn Abi Talib Rafsanjan Hospital. 3) The climate parameter has not been considered in the data set of the investigation to discover the hidden relationships of this parameter with the kidney disease.

Results: The results of the experiments in this study showed that the proposed prediction model using the Bayes method and eight identified key features (age, renal biopsy, uremia, sedimentation, albumin, edema, nocturnal enuresis, and urine-specific gravity), can detect kidney disease in people of different clinical characteristics, with 99.38% accuracy. Conclusion: Considering that the early diagnosis of kidney disease and the adoption of appropriate treatment methods can prevent the progression of kidney damage, in this study, an attempt has been made to achieve this goal by using new statistical methods and artificial intelligence techniques. Based on the proposed method and the conducted experiments, the most important features and the best data mining method were obtained, and finally, kidney disease prediction was possible with high accuracy.

Background: Considering the high prevalence of breast masses and the importance of screening and follow-up for malignancies in women, and since age and hormonal changes during menopause play a role in determining the type of pathology and prognosis of the masses, the purpose of this study is to determine the relationship between menopause and mass pathology.
Methods: This was a cross-sectional-analytical study that was conducted in order to investigate the types of pathology of breast masses and their relationship with the age of menopause in women referred to Shahid Beheshti Hospital in Qom between April 2013 and April 2019. The inclusion criteria include: having sufficient file information and having a contact number to complete personal information, no history of cancer in other parts of the body and simultaneous malignancies, and the exclusion criteria also include: samples that were taken by cellular aspiration sampling, There were women who had a history of first-degree breast malignancy and were previously diagnosed with breast cancer and there was a possibility that the new mass under study was metastatic. Finally, the patients' information was extracted from the files and recorded in pre-prepared checklists. And the supplementary information of the incomplete files was asked and completed using the contact information of the patients. After collecting the information, using SPSS software version 26 and with chi-square and t-test statistical tests and considering the significance level of 0.05 the data was analyzed.

Results: He prevalence of malignancy in postmenopausal women was higher than in premenopausal women. Also, a significant difference was found between tumor size, the presence or absence of metastasis, and menopause (P<0.05), but no significant difference was found between tumor location and menopause (P>0.05). Conclusion: Breast malignancies (invasive ductal carcinoma, invasive mixed carcinoma, mucinous, medullary, and papillary carcinoma) were more common in postmenopausal women than non-menopausal women. In both groups, ductal dilatation and chronic inflammation were the most benign findings, and fibroadenoma was found at a much lower rate in menopausal women than in non-menopausal.