Tehran University Medical Journal

Background: Aberrant pre-mRNA alternative splicing is a common event in cancer cells. Many abnormally spliced RNA variants have been observed in tumor cells and they can be used as biomarkers or therapeutic targets in new drug design. Increasing our knowledge in understanding the mechanisms of alternative pre-mRNA splicing for cancer-related genes and determination of cancer specific isoforms are important for the development of new strategies in cancer therapy. The aim of this study was isoforms identification and expression of PIK3CA, FGFR3 and FGFR1 genes in bladder cancer by RNA Sequencing and Real-Time PCR.
Methods: This cross-sectional study was conducted at Urology Research Center of Sina Hospital, Tehran University of Medical Sciences, Tehran, from September 2014 to October 2016. Paired tumor and adjacent normal tissues samples were obtained from 30 bladder cancer subjects. Total RNAs were extracted from bladder tumor and normal tissues. Quantitative and qualitative examinations have been done. After quality control, fragmentation of RNAs and cDNA library construction, next-generation RNA sequencing was performed. Resulting raw data were analyzed with different bioinformatics software. Differential expression was confirmed by Real-Time PCR.

Conclusion: RNA sequencing make possible to do the accurate assessment of transcript abundance and identification of different isoforms resulted from aberrant pre-mRNA alternative splicing, which is a crucial process for the maturation of transcripts of multi-exon genes. Regarding the differences in isoforms expression in tumor and normal tissues of bladder cancer, they have potential to be used as biomarkers and sensitive targets for cancer therapy.

Background: Head and neck squamous cell carcinoma (HNSCC) is the malignancy of squamous cells (the epidermal layer of skin) in cavities in head and neck includes: larynx, pharynx, paranasal sinuses and oral cavity. The main goal of this research was to understand the effect of mutations in two important genes (KRAS and BRAF) in RAS/MAP kinase (EGFR) signaling pathway in tumor cells with head and neck squamous cell carcinoma in Iran.
Methods: The present cross-sectional study performed from October 2015 to September 2016 on 40 patients suffering from head and neck squamous cell carcinoma, all confirmed by pathology department of Imam Khomeini hospital. Tumor samples were achieved from the surgical cancer department of Imam Khomeini hospital and stored in liquid nitrogen until starting tests. The tests done in genetic laboratory of Tehran University of Medical Sciences. Techniques we used in this research, were DNA extraction based on phenol-chloroform approach, Multiplex PCR (M-PCR) to amplify mentioned exons and KRAS/BRAF strip assays to detect mutations in mutated hotspots in exon 2 of KRAS and codon V600E in BRAF gene.
Results: In this study, we observed 7 mutations in codons 12 and 13 exon 2 in KRAS gene (about 17.5%) and 4 mutations in codon V600E in BRAF gene (about 10%) of obtained tumor samples. The hotspot mutation in codon 12 were Asp (10%) and Ser (5%) respectively. In BRAF, the most common mutation, as we expected according to other researches, was observed in codon V600E. We also observed that 29 people of these patients were male (about 72.5%) and 11 patients were female (about 27.5%). Moreover, 28 patients were over 50 years, while 7 patients were below the age of 50.
Conclusion: The results of this study showed that mutations in genes KRAS and BRAF especially in studied hotspots, and the effects on their molecules in EGFR signaling pathway are important in involving head and neck squamous cell carcinoma, as other cancers. These findings may be considered in choosing drugs for targeted chemotherapy.

Background: The causes of Attention-deficit/hyperactivity disorder (ADHD) (the most common psychological disorder is still unknown. The main symptoms include impulsivity, hyperactivity and attention deficit. Some studies have shown the relationship between ADHD and oxidative stress, and yet some researches have shown the effects on vitamin D on the antioxidants level. This research intends to identify the effect of vitamin D supplementation on the antioxidant serum level in 6-13 years old children with ADHD.
Methods: This double blind clinical trial was conducted in Isfahan city, the center of Iran, from October 2015 to February 2016. The sample included 35 subjects of both groups that were randomly selected among 6-13 years old children with ADHD diagnosed by pediatric psychologist. The intervention group consumed 1000 IU of vitamin D3 daily for three months, and the control group used placebo for the same period of time. Their stature and weight were recorded by digital instruments without the shoes with the least clothes. The next step was to train the food record of the students to the parents so that 3 food records were taken during the study. 25-hydroxyvitamin D3 (25(OH)D3), TAC (Total antioxidant capacity), MDA (Malondialdehyde), CAT (Catalase) and GSH (Glutathione) of the participants of both groups were measured before and after the intervention.
Results: In this Study, both groups were adjusted in terms of their age, gender and BMI. The mean score of the variables of leisure time and sport showed no significant difference in the both groups. Comparing the average TAC and MDA between the two groups before intervention didn’t show a significant difference (P1TAC=0.06) (P1MDA=0.32), but after the intervention, the vitamin D intake group showed the increase in TAC and decrease in MDA (P2TAC=0.001) (P2 MDA=0.01). Moreover, CAT and GSH showed no significant difference in the two groups before and after intervention.
Conclusion: Vitamin D supplementation for 3 months led to the improvement of antioxidant capacity by the increase of TAC and decrease of MDA, but the CAT and GSH showed no significant change in the mentioned period of time.
 

Background: Bloodstream infections are the most important causes of morbidity and mortality in hospitalized patients. Blood culture plays an important role in identifying most of bacterial agents of bloodstream infections. Knowledge about bacterial agents of bloodstream infections and also antibiotic resistance of these bacteria are important. Antibiotic resistance among bacterial agents of bloodstream infection including Acinetobacter, Klebisella, Pseudomonas, Escherichia coli, Enterobacter, Enterococcus, Staphylococcus aureus and Staphylococcus coagulase negative (CoNS) is one of the major challenges faced by physicians in treating. Therefore, this study was aimed to determine the frequency and antibiotic resistant patterns of bacterial isolates from hospitalized patient's blood cultured samples in the hospital, Tehran, Iran.
Methods: This research is a descriptive and retrospective study based on recorded data in Shariati hospital laboratory and under the supervision of Tehran University of Medical Sciences. The bacterial isolates were collected from positive blood cultures from October 2013 to March 2014. The frequency of bacterial isolates were determined by phenotypic and biochemical tests. The antibiotic resistance patterns of isolated bacteria were found by disk diffusion agar method. The diameters of inhibition zone were recorded and interpreted according to Clinical and Laboratory Standards Institute (CLSI) 2013.
Results: The frequency of bacterial isolates was determined among 595 positive blood cultures as followed: 41% Pseudomonas, 20% Staphylococcus epidermidis, 10% Escherichia coli, 6% Acinetobacter lwoffii, 6% Staphylococcus aureus, 5% Stenotrophomonas, 3% Acinetobacter baumannii. The antibiogram test showed that 96.2% of Acinetobacter lwoffii, 92.8% of Acinetobacter baumannii, 66% of Pseudomonas aeruginosa, 85.7% of Staphylococcus epidermidis, 65% of Staphylococcus aureus, 75% of Klebsiella, 73.7% of Escherichia coli, and 50% of Stenotrophomonas were resistant to imipenem, piperacillin, piperacillin, erythromycin, erythromycin, ciprofloxacin, trimethoprim-sulfamethoxazole, and ceftazidime respectively.
Conclusion: The most prevalent bacterial isolate among the blood cultures of patients was Pseudomonas. The patients more than 50 years were more susceptible to blood stream infections. The most bacteria were isolated from the internal medicine department of hospital. The antibiotic resistance was also increasing especially in Acinetobacter, Staphylococcus coagulase negative, Escherichia coil and Klebsiella

Background: Renal artery stenosis (RAS) is a known cause of secondary hypertension and renal failure. The most patients with renal artery stenosis are asymptomatic. So, the exact prevalence of this disease is unknown. The gold standard of diagnosis of RAS is renal angiography that is an expensive somewhat hazardous procedure and may revealed nothing. The aim of this study was to develop a simple risk model score to predict significant RAS based on known risk factors. This may enable us to select patients with high probability of having RAS to perform angiography.
Methods: A total of 4177 patients whom underwent renal angiography from April 2001 to March 2016, were randomly assigned to a development and a validation dataset in ratio of 2:1 respectively. The clinical and laboratory data of patients were analyzed by multivariate regression analysis. The factors of female sex, history of hypertension and glomerular filtration rate were determined as predicting factors and they were assigned a weighted integer, the sum of the integers was a total risk score for each patient. This model was examined at validation set.
Results: We retrospectively evaluated all patients undergoing renal artery angiography since 15 years ago. We extracted all risk factors of RAS including age, sex, height, weight, and history of diabetes, hypertension and hyperlipidemia. We also looked at coronary or peripheral vascular diseases and presence of heart failure. The age of patients was 63.5±11.2 years and 40% of the patients were female. The significant RAS was defined as 70% or more narrowing of renal artery. The prevalence of renal artery stenosis was 14.4% and 13.5% in development and validation dataset respectively. The area under curve and confidence interval for final mode in development dataset was 67.9% (65.0-70.8%). The rates of RAS increased with increasing risk score. In 1402 patients in validation dataset the model showed good discrimination power (cstatistic= 0.76)
Conclusion: This model simply assesses the risk of RAS using available information. This model can be used both in clinical and research purposes. The power of model for diagnosis of RAS is estimated to be 72.6% (68.8%-76.4%).

Background: Rash is a common complaint in children that has many causes and the various differential diagnoses. Therefore, urgent and appropriate clinical diagnosis is necessary to provide immediate medical intervention. Therefore, the purpose of this study was to investigate the causes of skin rash in children hospitalized due to rash.
Methods: This descriptive-analytic study was performed on all patients admitted for skin rashes in Hazrat Masoumeh Hospital in Qom, Iran from 2010 to 2015. In this study, the data of 317 patients who were admitted to the early diagnosis of rash were collected from patients' files and recorded in the checklist.
Results: According to our study, the most common causes of skin rashes in children were viruses with a share of 40.69% (129 cases), allergic causes being as prevalent as 21.77% (69 cases) and drug induced rashes that accounted for 20.50% (65 cases). Based on the site and type of rashes, the most common type of rashes were maculopapular rashes with 42% and hives with 31.9% prevalence, and the most common site of involvement was diffuse involvement that would account for 84% of the cases. In terms of drug use history, 35.6% had a history of antibiotic use prior to admission, and 14.5% had an antiepileptic drug use history. There was a significant relationship between the cause of rashes and the season of presentation (P< 0.05) as well as the age of presentation (P< 0.05).
Conclusion: This study showed that there is a significant relationship between the season and age of occurrence, but the use of these factors as a benchmark for the diagnosis of rash requires more studies. Paying attention to the causes of rash in children, knowing about these factors, and continuous evaluation of these patients can help in advancing a proper management of the problem of patients. The most frequent factors were viruses and then allergic and pharmaceutical agents, and the most common type was maculopapular.

Background: Using natural compounds with low toxicity on normal cells and high efficacy on malignant cells is highly appreciated for treatment of colorectal cancer (CRC). In the present study, the effect of fish-oil derived eicosapentaenoic acid (EPA) on the cell number, cell proliferation rate and caspase-3 enzyme activity in LS174T human colorectal cancer cell line was investigated.
Methods: This experimental study was performed in cell culture lab, Institute of Biotechnology, affiliated to the Urmia University, Urmia, Iran from April to September 2017. LS174T colorectal cancer cells at a density of 5×105 cells per well were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS) and kept at 37 °C in a humidified incubator with 5% CO2 for 24 hours. Thereafter, the cells were treated with 50, 100, 150 and 200 μmol EPA for 48 hours and cell numbers were counted using neobauer chamber and caspase-3 activities were measured by performing the caspase-3 colorimetric assay (Abcam, Cambridge, MA, USA). Furthermore, 5×103 LS174T colorectal cancer cells were cultured and treated with the above-mentioned EPA concentrations for 24, 48 and 72 hours, after which cell proliferation rate was evaluated by WST-1 proliferation assay (Roche Diagnostics, Mannheim, Germany).
Results: Treatment of LS174T colorectal cancer cells with 50, 100, 150 and 200 μmol EPA decreased the number of cells in a dose-dependent manner. We also found that treatment of malignant cells with increasing EPA concentrations (50 to 200 μmol) significantly decreased cell proliferation in a dose and time dependent manner. After a 72 hours treatment of LS174T cells with 200 μmol EPA, cell proliferation was calculated to be 30.3% compared to untreated control cells. Following 48 hours treatment, caspase-3 activity increased with increasing EPA concentrations in which at 200 μmol EPA, caspase-3 activity increased by 3.4 fold compared to untreated control cells.
Conclusion: Fish-oil derived eicosapentaenoic acid as a safe compound decreases the number of colorectal cancer cells and their proliferation rate and activates caspase-3 enzyme, as an executor protein in apoptosis.

Background: Each toxic agent results in unique presentations, depending on what neurophysiological changes occur following exposure. Scientific understanding of lead toxicity in the organ systems and at low levels of exposure continues to evolve. However, effects of lead poisoning on the thyroid gland function are controversial. In this descriptive study, changes in thyroid hormones in patients with lead poisoning were compared with patients with opioid addiction and healthy individual who were matched for age and sex.
Methods: In this descriptive study, which was conducted from March 2016 to February 2017 in Loghman Hakim Hospital in Tehran, ninety patients were evaluated using convenient sampling method for lead and thyroid hormones levels. The levels of lead and thyroid hormones were evaluated using standard laboratory method, in thirty male patients with lead poisoning, thirty male patients with opioid addiction referring to addiction treatment center and thirty healthy male referring to a blood donation center who were matched for age. Thyroid function parameters in patients with lead toxicity were compared with those of control groups.
Results: The lead level in the lead toxicity group was 57.5±23.5 µg/dl, in the first control group with opium addiction 7.8±3.8 µg/dl and in the healthy male referring to a blood donation center, 5.9±9 µg/dl. Thyroid stimulating hormone (TSH) was significantly lower in patients with lead poisoning (0.2±0.01 Milli-International Units Per Liter (mIU/L) than in the patients with opioid addiction (2.4±1/05 mIU/L) and healthy male referring to a blood donation center (2.3±0.01 mIU/L) (P= 0.04), and thyroxine hormone (T4) was significantly higher in patients with lead poisoning (17.8±2.6 µg/dl) than in the patients with opioid addiction (8.8±1/9 µg/dl) and healthy male referring to a blood donation center (7.4±3.5 µg/dl) (P= 0.02).
Conclusion: Lead toxicity has an effect on thyroid function and it reduces thyroid stimulating hormone and increases thyroxin levels. Clinicians should be aware of the potential hazardous effects of lead on the thyroid and mechanisms through which lead causes these effects on thyroid function need to be elucidated.

Background: Escherichia coli (E. coli) is one of the most important infectious agents in patients undergoing prostate biopsy. It belongs to a large family of gram-negative rods, Enterobacteriaceae. This family includes members of the normal flora of the intestine that are only occasionally pathogenic. Recent considerations of rectal colonization with fluoroquinolone-resistant E. coli shows the need to change strategy of treatment of infection in patients undergoing prostate biopsy. Therefore, the purpose of this study was to determine molecular typing of fluoroquinolone resistant (FQR) E. coli rectal isolates and associated infections in patients undergoing prostate biopsy.
Methods: In this prospective cohort study, rectal swabs were collected from 158 male patients before prostate biopsy at the Urology Research Center of Sina Hospital, Tehran, Iran, from March 2015 to February 2016. The FQR organisms were isolated using selective media, and antibiotic susceptibility pattern was determined for following antibiotics, ampicillin, levofloxacin, cotrimoxazole, amoxicillin-clavulanate, cefazolin, ceftazidime, cefepime, gentamicin, piperacillin-tazobactam, nitrofurantoin, amikacin, fosfomycin, imipenem. In general, phylogenetic background, prevalence of E. coli sequence type 131 (ST131) and its subclones (H30 and H30-Rx ST131) were compared in two groups of FQR E. coli rectal colonization and clinical isolates.
Results: In total, 73 patients had a positive rectal culture for FQR gram-negative bacteria, the most prevalent isolate of which was E. coli. Phylogenetic group B2 was most predominant, followed by A, E, C and D, B1 and F. The antibiotic susceptibility patterns for the FQR organisms showed high levels of resistance to ampicillin and trimethoprim-sulfamethoxazole, while the resistance to amikacin, fosfomycin and imipenem remained very low. In general, antibiotic resistance to several antibiotic was mainly detected in group B2 and with ST131 genotype. Despite the increase in infections among patients colonized with strains of E. coli ST131, its frequency was almost statistically significant between colonized and infected groups.
Conclusion: The ST131 pathogen has a high prevalence in rectal colonization and post prostate biopsy infections, which showed widespread resistance to common antibiotics.

Background: Asymptomatic hemorrhagic transformation infarct (AHTI) is known as a complication of ischemic attack and maybe occurs in the entire stroke. However, the role of AHTI in the result of the treatment is still not clear, because it is based on the definition of an asymptomatic and not identifiable. The aim of this study was assessment and evaluation frequency of AHTI in acute ischemic stroke patients.
Methods: This prospective cross-sectional study was done in Neurologic Department, Tehran University of Medical Sciences, Tehran, Iran, from April 2015 to April 2016. Second evaluation was done about new neurologic signs and symptoms ten days after stroke. In addition, brain CT scan was used to diagnose of hemorrhagic event in infarct area. If the hemorrhagic event was occur in different area, the patient was consider as a non-hemorrhagic transformation and excluded from the study. Other exclusion criteria include intracranial hemorrhage (ICH), trauma to the head during admission, cerebral vein thrombosis, coagulation disorder, anti-coagulant (heparin, warfarin) administration, induced transformation within 10 days of onset of ischemia, lacunar ischemic and unobservable in thirty T-brain scan, patient's lack of referral for examination and CT scan 10 days after the onset of symptoms, died before CT was considered.
Results: Three hundred and eighty seven patients had inclusion criteria. 249 cases were excluded due to lost following, vein thrombosis of the brain, lacunar ischemia, anti-coagulants recipient (heparin, warfarin), asymptomatic hemorrhagic transformation and death. Finally, 138 cases (86 men, 52 women) with 66.61±9.37 years (50-101 years) were participated in data analysis. Frequency of positive CT scan was evaluated for ischemic stroke evidence in two stages. Of the 138 patients who participated in the study, 75 (54.3%) were positive in the first and 63 (45.7%) cases in the second time. 27 cases (19.6%) had AHTI.
Conclusion: Coronary artery bypass graft (CABG) had significant correlation with ATHI in acute ischemic attack. However, stroke history correlated with decreasing of ATHI. Concerning smoking and consuming the results showed that smoking did not affect the asymptomatic hemorrhagic transformation. Also, the results showed that the use of aspirin and Plavix also had no significant effect on increasing the incidence of ATHI.

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: Although significant advances have been made in scientific and medical technology, but the rate of medical complaints has also risen. The purpose of this study was to investigate the effect of handling of medical malpractice cases in the hospital complaints committee on the reduction of patient complaints to law enforcement authorities.
Methods: In this descriptive study, patients complained about ophthalmology from April 2005 to December 2005 at Farabi Hospital, Tehran, were evaluated. The complainant's patients, if confirmed by the trusted doctors, were invited to complaints committee, and the subject of the complaint was examined and tried to obtain patient satisfaction.
Results: A total of 87 patients complained to ophthalmologists completed a complaint form 71 (81.7%) of the cases were male. Statistically, the number of complaints was significantly lower in those with lower education (P=0.02). The prevalence of primary disease, 52 cases (59.8%) was cataract and 14 cases (16%) due to refractive errors and refractory surgery. In the examination of complaints by trusted doctors in the hospital, 11 cases of ophthalmologic error were identified, with a mantle rate of 12.6%, and the cases were reviewed by the complaints committee. Of the cases of complained that confirmed by the committee, only one person sued the law enforcement, which represented 9% of the defaulted item. These statistics showed a significant decline compared to the past year at the same center, and the percentage of defaults to law enforcement was 37.5% (P<0.05).
Conclusion: Establishing committees to handle complaints of ophthalmologic failures in hospitals and providing a clear and honest atmosphere to hear the subject of complaints by patients and their companions, and then trying to get patients' satisfaction and helping them continue their treatment can lead to reduced complaints of patients to the authorities Legal, like forensics medicine department and medical council. 

Background: Growth disturbance is a common phenomenon in children with congenital heart diseases (CHD). Malnutrition and nutritional disturbances have a higher prevalence among children with down syndrome, especially children with Down syndrome; on the other hand, the prevalence of CHD is higher among syndromic children, which needs surgical repair as the definitive treatment. The nutritional status plays an important role in determining the postoperative complications and recovery. The purpose of this study was to investigate the growth status of children with Down syndrome and congenital heart disease before cardiac surgery.
Methods: This study was conducted as a retrospective study by evaluating the records of all syndromic patients undergoing cardiac surgery at Children’s Medical Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran, from March 2011 to March 2017. Age, weight, height, weight-for-age z-score (WAZ), weight-for-height z-score (WHZ), height-for-age z-score (HAZ), mortality and hospitalization rate in an intensive care unit (ICU) were recorded in these patients. The z-scores more than -1 were considered as normal, between -1 and -2 as mild malnutrition, between -2 and -3 as moderate malnutrition and below -3 as severe malnutrition.
Results: 35 (51.5%) patients were female and 33 (48.5%) were male. The mean age, weight, and height of these children were 26.9±24.9 months, 9.1±4.95 kg, and 79.55±17.95 cm, respectively. The mean of WHZ, WAZ, and HAZ in these children was -2.18+1.65, -1.95+2.25 and -1.22+3.11, respectively. Based on the values of WAZ, WHZ, and HAZ, 85.3%, 77.9% and 75% of patients have malnutrition (mild to severe forms, z-score less than -1). The most common cardiac defect was ventricular septal defect (VSD) accompanied by pulmonary arterial hypertension.
Conclusion: Considering the high prevalence of impaired nutritional status in these children and considering the effect of preoperative malnutrition on surgical outcomes, including mortality, assessing the nutritional status is much important. The adequate nutritional support in these patients leads to a reduction of the mortality, postoperative complications and morbidities.

Background: Congenital heart diseases are the second group of congenital anomalies in infants. These disorders are a major cause of death in the first year of a child's life. Early detection helps to treat these diseases better. In this study cardiology consultations of hospitalized infants in the neonatal intensive care unit were evaluated.
Methods: In this cross-sectional study, two hundred and fifty pediatric cardiology consultations conducted in Shahid Beheshti Hospital in the year 2012 were reviewed. Information such as the cause of consulting, delivery type, age of parents, relative couples, family history of congenital heart disease, maternal medications, maternal background diseases, the final diagnosis, and prognosis follow-up of the patients were recorded in a designed questionnaire. Finally, the data were entered into the SPSS software, version 16 (IBM SPSS, Armonk, NY, USA) and analyzed using descriptive statistics and chi-square test. P-value of less than 0.05 was considered significant.
Results: The mean age of the consulted neonates was 4.845±5.14 days with a gestational age of 33.933±3.65 weeks. Male sex and cesarean section were the most frequent. Fifty-six percent of consulted infants were male. The present study revealed that prematurity (76%), murmurs (30.8%), respiratory distress syndrome (14.4%) and cyanosis (13.2%) were the most common causes of the cardiac consultation seeking among infants. Seventy-six percent of infants were consulted due to prematurity. Eighty-four percent of infants had a normal conditions. Septal defects (ventricular or atrial septal defect) and patent ductus arteriosus were the most common disease diagnosed with the prevalence of 27.5 and 17.5%, respectively. There was a significant relationship between preterm labor and congenital heart disease (P<0.001). Additionally, prematurity associated with respiratory distress syndrome and using assisted reproductive techniques.
Conclusion: The higher prevalence of congenital heart disease in the present study, compared with other studies, reflects the fact that cardiology consultation based on clinical suspicion leads to the more identification of congenital heart disease that means the right referral of newborns for consultation was accompanied with a higher incidence of heart failure.

Behçet's disease (BD), also known as the Silk Road disease, is a multisystemic and rare inflammatory disorder primarily prevalent in populations along the Mediterranean Sea. Today, BD is defined as a crossroad between autoimmune and auto-inflammatory syndromes. Variety of syndromes including mucocutaneous manifestations such as oral and genital ulcers, papulopustular lesions and erythema nodosum as well as ocular, vascular, gastrointestinal and nervous system occur. The disease etiology has not yet been elaborated, though researchers have reported several reasons that can increase the likelihood of the disease occurrence including a genetic factor, human leukocyte antigen HLA-B51 (B51) antigen, infectious conditions such as herpes simplex virus (HSV), those involved in inflammatory and autoimmune conditions such as imbalance of various cytokines and immune cells levels as well as existence of various gene variants. Among the various immuno dysfunctions that are found in BD, patients have increased neutrophil motility and superoxide production, as well as elevated production of tumor necrosis factor (TNF)-α and decreased production of interleukin-10 (IL-10). Since vasculitis and tissue damage is usually seen with Behcet disease, unusual concentrations of chemokine and adhesion molecules can also help us understand the causes of disease. Among the functional deficiencies of the immune system, increased concentrations of neutrophils and monocytes are of importance leading to an increase in reactive oxygen species (ROS). Behcet's disease has common characteristics with some immune-mediated diseases such as systemic lupus erythematosus (SLE), psoriasis, ankylosing spondylitis, and inflammatory bowel disease (IBD), which suggests that they may share similar etiologies and genes. Genetic and epigenetic modulations have also been proposed as involved in the pathogenesis of BD. Modifications in DNA methylation have been found in BD patient monocytes and lymphocytes, leading to the adverse function of these cells. The positive replies to classical immunosuppressive agents like cyclosporine and azathioprine and participation of autoantigens at the beginning of the illness are the chief BD features that reflect the autoimmune nature of the disorder. This review article attempts to introduce the BD disease and its contributing factors with emphasis on the role of different cells and cytokines based on updated studies.

Background: Prostate cancer has been reported as a worldwide important kind of cancer and the second most common cause of cancer-related mortality among men. Prostate-specific antigen (PSA) serum level is one of the most important markers of prostate cancer diagnosis. While PSA level helps predict the risk of prostate cancer development, researchers still looking for ways to increase the accuracy of prognostic models. To increase the specificity of PSA and decrease of unnecessary biopsies and morbidity, PSA-related parameters such as PSA doubling time (PSADT) have been used. In this study, the relationship between this factor and the severity of prostate cancer was evaluated.
Methods: In this retrospective study, the data of patients who were subjected to transrectal ultrasound-guided (TRUS) biopsy of the prostate and referred to Imam Khomeini Hospital, Tehran, between 2009 and 2017 were reviewed. We enrolled the men with at least two consecutive elevated PSA level within three months to calculate PSADT. Based on the pathology report, primary and secondary Gleason score (GS) were determined. Correspondingly, considering GS, the patients were divided into two groups with high-grade and low-grade tumor (GS<7 considered as low-grade and GS>7 considered as high-grade tumor).
Results: Totally, 1712 cases of TRUS biopsy of the prostate were studied. Among them, 547 (32.3%) had prostate cancer, of whom 73 cases were eligible based on inclusion criteria and were consented to enroll in the study. According to the data obtained, we found a significant difference in PSADT between the two groups of patients with high-grade and low-grade malignancy (mean±SD PSADT, 9.8±14.2 vs. 16.1±14.9 respectively, P=0.004). Considering the seven months as the cut-off point for PSADT in determining malignancy, there was a significant difference between the two groups according to Fisher's exact test (P=0.01).
Conclusion: In our study, PSADT cut-off of 7 months provided the greatest accuracy for differentiation between low-grade and high-grade malignancy, and PSADT has acceptable accuracy for the diagnosis of high-grade tumors.

Background: Skeletal muscle mass, which is regulated by a balance between muscle protein synthesis and degradation, is an important factor for movement to meet everyday needs, especially in pathological conditions and aging. The purpose of the present investigation was to compare the alterations of the gene expression involved in muscle protein synthesis and degradation signaling pathways induced by two exercise training protocols.
Methods: Eight weeks old Wistar rats have been assigned to the present experimental study, which was conducted from August 2018 to October 2018 at the animal laboratory of Tehran University. They were randomly divided into two resistance and endurance training groups and one control group, and run on a treadmill, 5 sessions per week for 8 weeks. 48 hours after the last exercise session, the rats in the two groups were anesthetized, and the dissected soleus muscles from euthanized animals were stored at -80° for RT-PCR and Western blot analysis later. Between-group differences were analyzed by the parametric and non-parametric tests for normally and non-normally distributed data respectively, at the significance level of α˂0.05.
Results: Compared with the control group, mTORC1 gene expression was increased significantly just in the endurance group (P=0.022), whereas both endurance and resistance exercise protocols caused a significant increase in Rps6kb1 (P˂0.001 and P=0.001 respectively). In protein degradation pathway, although, FOXO3a did not alter significantly (P=0.463), eIF4Ebp1 gene expression was inhibited by both endurance and resistance exercise training protocols (P˂0.001 and P=0.001 respectively). The alterations of Rps6kb1 and FOXO3a gene expression were confirmed by Western blot analysis.
Conclusion: The results showed that the exercise training protocols of the present study had approximately similar effects on alterations of gene expression involved in skeletal muscle protein synthesis and degradation pathways. Therefore, application of the protocols may be considered to prevent or reduce the muscle atrophy in pathological conditions such as motor neuron disease, aging, and/or muscle strength improvement in athletes.

Background: Botulism is mostly caused by Clostridium botulinum neurotoxin which has been described as a bilateral symmetric descending flaccid paralysis. Preventing and responding to botulism outbreaks is a public health emergency. In this study, the disease is reported in a family.
Methods: In a case series study, during an outbreak, four members of a family with symptoms including paralysis, ptosis, blurred vision, diplopia, weakness, dysphagia, dry mouth, respiratory problems, vertigo, and lethargy, referred to Loghman Hospital of Tehran. Among the patients was an elderly woman and a pregnant woman. All clinical signs and symptoms of the patients were recorded daily in a researcher-made questionnaire from 27 August to 3 September 2018. At the time of admission, vital signs (pulse rate, respiration rate, and body temperature) of patients were stable and within normal limits. Following clinical suspicion of food-borne botulism in these patients, samples of the first two patients, including serum, stool, gastric secretions, and homemade whey were sent to the Botulism Laboratory of Microbiology Department of Pasteur Institute of Iran for the mouse bioassay.
Results: Type A neurotoxin was detected in homemade whey after the mouse bioassay. Therefore, foodborne botulism was confirmed in patients with laboratory results. Patients included two men and two women with a mean age of 52.7 years old. The length of hospitalized days was between 2 and 6 days. Two of the patients were admitted to the intensive care unit (ICU). Patients under study were fully recovered with timely diagnosis of the disease, treatment with antitoxin, and supportive care.
Conclusion: When conscious patients referred to the hospital with symptoms of paralysis, foodborne botulism is an important differential diagnosis. On-time diagnosis and antitoxin treatment can prevent serious complications.

Background: Common treatment for infertile couples is the use of controlled ovulation hyperstimulation (COH) with intrauterine inseminations (IUI). IUI is used in cases such as ovulatory dysfunction, cervical factor infertility, male subfertility, and unexplained infertility. In this study, we evaluated the relationship between IUI outcome and special causes of infertility.
Methods: This was a cross-sectional study and a sampling method was available in this study, from January 2014 to August 2016, 994 cycles in 803 infertile couples referred to Royan Research Institute in Tehran were analyzed. Inclusion criteria were: male factor infertility, combined causes, ovarian disease, and infertility of unknown cause. To evaluate pregnancy, 12-16 days after IUI, it was considered positive if pregnancy test followed by transvaginal ultrasound at week 4 after IUI were positive.
  Data were analyzed using SPSS software, version 20. T-test and chi-square were used to compare the case and control groups. Linear-by-linear test was also used to calculate the relationship between female age and clinical and multiple success rates. P<0.05 was considered significant for the results of these tests.