Tehran University Medical Journal

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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.

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Results: The patients included 42 (75%) men and 14 (25%) women with the mean age of 49.5 years (9 to 90 years). Positive culture was observed in 9 cases but, only in one of these patients direct examination was positive and fungal elements were seen in 10% KOH preparation. Though, fungal keratitis was confirmed in 9 (16%) patients including seven (77.8%) men and two (22.2%) women. The majority of cases (88.9%) had a history of corneal trauma with plants and they were mainly farmer. According to statistical analysis, there was a significant association between corneal trauma and keratomycosis (P=0.007). The most common etiologic agents were Fusarium spp. (n: 4, 44.4%), followed by Aspergillus flavus (n: 2, 22.2%), Penicillium sp. (n: 1, 11.1%), Acremonium sp. (n: 1, 11.1%), and Cladosporium sp. (n: 1, 11.1%) respectively. Conclusion: In the presence of sufficient predisposing factors such as corneal injuries caused by plants, keratomycosis could be caused by a variety of fungi. Furthermore, low sensitivity of direct examination in this study, revealed the necessity of culture in diagnosis of keratomycosis.

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Results: According to results, of the 661 patients who were studied, 462 ones had positive and 273 had significant prick test results. The grasses group with 293 positive (44.3%) and weeds group with 259 positive results (39.2%) were more common than the other categories. Among the significant positive tests, these two categories with 161 and 142 significant positive tests were indicated as the most common allergens. Respiratory allergens were also more common in patients with a family history of allergies in weeds and trees categories, but there was no significant difference in sensitization pattern according to the history of tonsillectomy. Conclusion: Patients in Ardabil with allergic rhinitis and asthma were more sensitized to weeds and grass mixtures. It is recommended to provide preventive recommendations to allergic patients and the development of localized skin testing packages and additional studies should be conducted focusing on these two categories of allergens.

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Results: The intra-rater reliability of standard deviation of the center of pressure sway velocity and amplitude of both directions in both groups were more than 0.75. The intra-rater reliability of the area of the center of pressure sway in the healthy and hyperkyphosis group were 0.42 and 0.38 respectively. Conclusion: Standard deviation of the amplitude and standard deviation of the velocity of the center of pressure sway can be considered as reliable variables for assessing static balance in young women with and without dorsal hyperkyphosis in future studies. However, the inconsistency of sway area especially in women with hyperkyphosis suggests that the use of it for differentiation between subjects and the assessment of the outcome of any interventions on the postural stability should be considered with caution.

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Cancer is the second leading cause of death in the United States and has become a health problem worldwide. The reported incidence of new cancer cases is estimated at 19.3 million, with a mortality rate of 10 million in the world in 2020. There are several therapeutic approaches for cancer, including chemotherapy. Chemotherapy is consuming anti-neoplastic drugs, alone or in combination. However, it causes damages to the normal cells and has many side effects. Cardiac complications are common side effects of some chemotherapy agents. Cardiac myocytes are potentially more susceptible to the long-term adverse effects of chemotherapy agents due to the less regeneration ability in cardiac cells. Moreover, heart muscle dysfunction (cardiomyopathy) and cardiovascular complications may occur in cancer survivors even a year after chemotherapy or radiation therapy and influence their quality of life. Anthracyclines are commonly used in chemotherapy; especially doxorubicin is the most widely used drug of this family. Doxorubicin is an effective anti-malignant agent prescribed for the treatment of some solid tumors (e.g. ovary, breast, and gastrointestinal cancers). Doxorubicin can cause several side effects, ranging from cancer treatment’s common side effects such as fever, nausea, and vomiting to lethal cardiac side effects. Assumed that doxorubicin has many therapeutic and cytotoxic mechanisms, cardiotoxicity induced by doxorubicin is very common and there is no reliable treatment for this problem. The cardiac side effects of doxorubicin during a chemotherapy regimen can be acute, chronic, or even gradually progressive and persistent after the termination of doxorubicin therapy. In patients undergoing doxorubicin therapy, reported symptoms are cardiac rhythm and blood pressure changes, pericarditis, myocarditis, cardiomyopathy, and congestive heart failure. The pathophysiology of doxorubicin-induced cardiotoxicity is very wide. Disruption of normal mitochondrial function, decreased amount of antioxidant factors, production of reactive oxygen species (ROS), an imbalance in calcium hemostasis, activation of inflammatory cytokines, targeting topoisomerase-IIβ (Top2b), and induced DNA damage are associated with doxorubicin-induced cardiotoxicity. Increased doxorubicin in mitochondria activates the redox cycle that ultimately leads to the production of reactive oxygen species in both normal and tumor cells. The present review aims to investigate the cardiotoxic mechanisms of doxorubicin and explain different types of doxorubicin-induced cardiotoxicity.

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Background: Traumatic Spinal Cord Injury (TSCI) is one of the catastrophic events, the rate of which has been growing compared to the past decades. Complications caused by TSCI have a wide spectrum and can range from complete paralysis to numbness of the limbs. Additional to the injury severity and disability of the patient, the recovery rate depends on the treatment strategies. Despite extensive efforts and research in this field, there are still few treatment options for TSCI patients. Controversial results have been reported, however, spinal cord decompression is the only certainty for the treatment of these patients. In the present study, patients with thoracic and lumbar fractures were undergone decompression, less and more than 24 hours, and the recovery rate (RR) was compared after 6 months.
Methods: In this study, patients with lumbar and thoracic fractures who were referred to the neurosurgery department of Ahvaz Golestan Hospital during May 2019 to December 2021 were included. Decompression was performed at the fracture level as a total and at the upper and lower levels of the fracture as a partial decompression. To evaluate fine motor movements, picking up a small object with toes and following a rectangular path were used. Also, the gross motor movements, upper and lower proximal and distal muscle forces were measured. Conclusion: This study showed that decompression<24 hours in TSCI is associated with a significant improvement in lower fine movements.
 

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