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Ameneh Jafari,1,2 Mostafa Rezaei-Tavirani,1 Samira Karami,3 Mohsen Yazdani,4 Hakimeh Zali,1,5 Zahra Jafari6 1Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 4Department of Bioinformatics, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran; 5Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 6 9Dey Manzariye Hospital, Isfahan University of Medical Sciences, Isfahan, IranCorrespondence: Hakimeh Zali Department of Tissue Engineering and Applied Sciences, School of Advanced Technologies in MedicineShahid Beheshti University of Medical Sciences, Tehran, IranTel +989123367156Fax +982122439848Email hakimehzali@gmail.comMostafa Rezaei-TaviraniProteomics Research Center, School of Allied Medical SciencesShahid Beheshti University of Medical Sciences, Tehran, IranTel +982122439787Email tavirany@yahoo.comAbstract: New cases of the novel coronavirus, also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are increasing around the world. Currently, health care services are mainly focused on responding to and controlling the unique challenges of the coronavirus disease 2019 (COVID-19) pandemic. These changes, along with the higher susceptibility of patients with cancer to infections, have profound effects on other critical aspects of care and pose a serious challenge for the treatment of such patients. During the COVID-19 pandemic, it is important to provide strategies for managing the treatment of patients with cancer to limit COVID-19-associated risks at this difficult time. The present study set out to summarize the latest research on epidemiology, pathogenesis, and clinical features of COVID-19. We also address some of the current challenges associated with the management of patients with cancer during the COVID-19 pandemic and provide practical guidance to clinically deal with these challenges.Keywords: coronavirus, SARS-CoV-2, cancer, pandemic, health care

Zahra Yazdani,1 Alireza Rafiei,1 Mohammadreza Yazdani,2 Reza Valadan1 1Department of Immunology, Molecular and Cell Biology Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; 2Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111, IranCorrespondence: Alireza RafieiDepartment of Immunology, Molecular and Cell Biology Research Center, School of Medicine, Mazandaran University of Medical Sciences, KM 18 Khazarabad Road, Khazar Sq, Sari, IranTel +981133543614Fax +98-11-3354-3087Email rafiei1710@gmail.comBackground: To date, no specific vaccine or drug has been proven to be effective against SARS-CoV-2 infection. Therefore, we implemented an immunoinformatic approach to design an efficient multi-epitopes vaccine against SARS-CoV-2.Results: The designed-vaccine construct consists of several immunodominant epitopes from structural proteins of spike, nucleocapsid, membrane, and envelope. These peptides promote cellular and humoral immunity and interferon-gamma responses. Also, these epitopes have a high antigenic capacity and are not likely to cause allergies. To enhance the vaccine immunogenicity, we used three potent adjuvants: Flagellin of Salmonella enterica subsp. enterica serovar Dublin, a driven peptide from high mobility group box 1 as HP-91, and human beta-defensin 3 protein. The physicochemical and immunological properties of the vaccine structure were evaluated. The tertiary structure of the vaccine protein was predicted and refined by Phyre2 and Galaxi refine and validated using RAMPAGE and ERRAT. Results of ElliPro showed 246 sresidues from vaccine might be conformational B-cell epitopes. Docking of the vaccine with toll-like receptors (TLR) 3, 5, 8, and angiotensin-converting enzyme 2 approved an appropriate interaction between the vaccine and receptors. Prediction of mRNA secondary structure and in silico cloning demonstrated that the vaccine can be efficiently expressed in Escherichia coli.Conclusion: Our results demonstrated that the multi-epitope vaccine might be potentially antigenic and induce humoral and cellular immune responses against SARS-CoV-2. This vaccine can interact appropriately with the TLR3, 5, and 8. Also, it has a high-quality structure and suitable characteristics such as high stability and potential for expression in Escherichia coli .Keywords: SARS-CoV-2, multi-epitope vaccine, structural proteins, humoral immunity, cellular immunity, adjuvant

BACKGROUND AND OBJECTIVE: Abnormal vaginal bleeding under the age of 10 is rare among girls. In such cases, local lesions, trauma, intra–vaginal foreign body, malignant genital tumors, and precocious puberty should be taken into account. Leech infestation is one of the rare causes of severe prepubertal vaginal bleeding. One case of prepubertal vaginal bleeding due to leech infestation is presented here. CASE REPORT: An eight–year–old girl referred to the emergency department after three days of painless vaginal bleeding. The bleeding was moderate during the first two days and the patient experienced intensified bleeding and large menstrual clots on the third day. The patient had no history of trauma, coagulation disorder, systemic illness, and drug use, but noted the history of swimming in the muddy creek within a few days before referral to the emergency department. After examining the genital system, a black mass with wavelike movements was observed in the lower one-third of the vagina, and a piece of it was slightly out of the hymen. The leech was removed by forceps without damaging hymen. After a short time, the bleeding stopped. On the next visit, the patient had no vaginal bleeding and was discharged without any problem. CONCLUSION: In cases of prepubertal vaginal bleeding, accurate examination of the genital system and evaluating the history of swimming or bathing in contaminated creeks, springs, qanats and pools are essential.

In order to manage a project with integrity, a cohesive communication is needed between its various sections; possible risks, identification of stakeholders, providing the necessary resources on time and managing their availability, focusing on the approved budget and satisfactory quality the project can be successfully done. In the recent year BIM has as new aspects to engineering and architecture, and has become an accepted platform for planning and executing construction projects and contributed to integration of various fields and. also, project management standards, such as PMBOK, have come to aid construction managers. Through the basic capacities of BIM, and questionnaires according to aspects of PMBOK, the present study tries to identify the superior effects of BIM on project management. Moreover, it seeks to recognize the most significant aspects of BIM application on project management. by employing the FANP-AVIKOR decision making method to prioritize the parameters of the collected results, the study’s conclusion will indicate that almost all of PMBOK aspects equally benefit from using BIM; in addition, it will show that 3D BIM capacities, including clash detection, plan correction, are superior in comparison with 6D BIM and 7D BIM capacities.

N-acetylcysteine (NAC) and vitamin D provide effective neuroprotection in animal models of severe or inflammation-sensitized hypoxic ischemic encephalopathy (HIE). To translate these FDA-approved drugs to HIE neonates, we conducted an early phase, open-label trial of 10 days of NAC (25, 40 mg/kg q12h) + 1,25(OH)(2)D (calcitriol 0.05 mg/kg q12h, 0.03 mg/kg q24h), (NVD), for pharmacokinetic (PK) estimates during therapeutic hypothermia and normothermia. We paired PK samples with pharmacodynamic (PD) targets of plasma isoprostanoids, CNS glutathione (GSH) and total creatine (tCr) by serial MRS in basal ganglia (BG) before and after NVD infusion at five days. Infants had moderate (n = 14) or severe HIE (n = 16), funisitis (32%), and vitamin D deficiency (75%). NVD resulted in rapid, dose-responsive increases in CNS GSH and tCr that correlated positively with plasma [NAC], inversely with plasma isofurans, and was greater in infants with lower baseline [GSH] and [tCr], suggesting increases in these PD markers were titrated by neural demand. Hypothermia and normothermia altered NAC PK estimates. NVD was well tolerated. Excluding genetic syndromes (2), prolonged ECMO (2), lost-to-follow-up (1) and SIDS death (1), 24 NVD treated HIE infants have no evidence of cerebral palsy, autism or cognitive delay at 24-48 months. These data confirm that low, safe doses of NVD in HIE neonates decreased oxidative stress in plasma and CNS, improved CNS energetics, and are associated with favorable developmental outcomes at two to four years.

Background: Renal transplantation has long been considered the gold standard medical care for patients with end-stage renal disease. Candiduria continue to be a significant complication for renal transplant recipients. The risk of infections depends on the amount of immunosuppression and exposure to the potential pathogens. Objective: Molecular identification of Candida species isolated from renal transplant recipients with candiduria. Methods: Between 2009 and 2014, 62 Candida isolates were collected from 485 renal transplant recipients. All isolates were identified by PCR-RFLP profiles after digestion with the restriction enzyme MspI. Results: C. albicans (44%) and C. parapsilosis complex (5%) had the most and the least prevalence, respectively. Male to female ratio was 26/36, ranging in age from 19 to 62 years. Conclusion: Due to the fact that candiduria is connected with increased mortality in renal transplant recipients, precise identification of Candida species by molecular techniques can lead to an appropriate therapy among high risk patients. C. albicans remains the most prevalent species isolated from renal transplant recipients, Nevertheless, the number of non-C. albicans Candida species looks to be emerging.

Background: It seems that serum vitamin D levels are one of the potential environmental factors affecting the severity of multiple sclerosis (MS). In this study, we aim to evaluate vitamin D levels in MS patients and healthy subjects and assess the relationship between vitamin D level and disability. Methods: In this case-control study, 168 rapid relapsing MS patients and 168 matched healthy controls were randomly included in this study. Demographic characteristics and serum vitamin D levels for patients and controls, as well as expanded disability status scale (EDSS), duration of disease and diagnostic lag for patients were evaluated. We followed up patients for 6 months and relapses were recorded. Results: The mean serum vitamin D levels were 19.16 ± 17.37 inpatients and 25.39 ± 19.67 in controls (P = 0.560). The mean serum vitamin D levels were 12.65 ± 13.3 in patients with relapses and 22.08 ± 18.22 in patients without any relapses (P < 0.001). There was no significant correlation between EDSS score and serum vitamin D levels (r = −0.08, P = 0.280). There was a significant positive correlation between EDSS score and disease duration (r = 0.52, P < 0.001). Conclusion: In conclusion, vitamin D level in patients with MS was significantly lower than the healthy subjects, but no significant relationship was found between vitamin D levels and disability. Our findings did not suggest a protective role for serum vitamin D levels against disability.

Three oral platelet P2Y12 inhibitors, clopidogrel, prasugrel, and ticagrelor, are available for reducing the risk of cardiovascular death and stent thrombosis in patients with acute coronary syndromes (ACS). We sought to compare the efficacy of these antiplatelet drugs in contemporary practice.\ud \ud Data were collected for 10 793 consecutive ACS patients undergoing coronary angiography at Sheffield, UK (2009–2015). Since prasugrel use was mostly restricted to the STEMI subgroup, clopidogrel and ticagrelor were compared for all ACS patients, and all three agents were compared in the STEMI subgroup. Differences in outcomes were evaluated at 12 months by KM curves and log-rank test after adjustment for independent risk factors.\ud \ud Of 10 793 patients with ACS (36% STEMI), 43% (4653) received clopidogrel, 11% (1223) prasugrel and 46% (4917) ticagrelor, with aspirin for all. In the overall group, ticagrelor was associated with lower all-cause mortality compared with clopidogrel (adjusted hazard ratio (adjHR) 0.82, 95% confidence intervals (CI) 0.71–0.96, p = 0.01). In the STEMI subgroup, both prasugrel and ticagrelor were associated with a lower mortality compared with clopidogrel (prasugrel vs. clopidogrel: adjHR 0.65, CI 0.48–0.89, p = 0.007; ticagrelor vs. clopidogrel: adjHR 0.70, CI 0.61–0.99, p = 0.05). Of the 7595 patients who underwent PCI, 78 (1.0%) had definite stent thrombosis by 12 months. Patients treated with ticagrelor had a lower incidence of definite stent thrombosis compared with clopidogrel (0.6% vs. 1.1%; adjHR 0.51, CI 0.29–0.89, p = 0.03). In the STEMI subgroup, there was no significant difference between the three groups (ticagrelor 1.0%, clopidogrel = 1.5%, prasugrel = 1.6%; p = 0.29).\ud \ud In conclusion, ticagrelor was superior to clopidogrel for reduction in both mortality and stent thrombosis in unselected invasively managed ACS patients. In STEMI patients, both ticagrelor and prasugrel were associated with lower mortality compared with clopidogrel, but there was no significant difference in the incidence of stent thrombosis.

Hydro-alcoholic fruit extract of Cordia myxa was considerably effective on curing acute inflammation in mouse model. Previous studies suggested significant anti-inflammatory activities as well as potential anticancer agent of α-amyrins in seeds. Inhibition of Cyclooxygenase-2 (COX-2) and 5-Lipooxygenase (5-LOX) is significant in cancer prevention and therapeutics although this inhibition with chemo-drugs has its own side-effects. It is shown that these enzymes pathways are related to several cancers including colon, breast and lung cancer. This study was conducted based on Cordia species' α-amyrins as a safer natural anti-cancer compound for inhibition of COX-2 and 5-LOX enzymes by molecular docking. The X-ray crystal structure of COX2 / 5-LOX enzymes and α-amyrins was retrieved and energetically minimized respectively. The binding site and surface of enzymes were detected. Docking studies were performed by AutoDock 4.2 using Lamarckian genetic algorithm (LGA). Finally drug likeness, molecular pharmacokinetic properties and toxicity of α-amyrins was calculated. Molecular Docking revealed hydrogen and hydrophobic interactions between α-amyrins with both active sites of COX-2 and 5-LOX enzymes. Interestingly, it covalently bonded to Fe cofactor of 5-LOX enzyme and chelated this molecule. Base on binding energies (∆G) α-amyrin has more inhibitory effects on 5-LOX (-10.45 Kcal/mol) than COX-2 (-8.02 Kcal/mol). Analysis of molecular pharmacokinetic parameters suggested that α-amyrins complied with most sets of Lipinski's rules, and so it could be a suitable ligand for docking studies. Eventually, bioactivity score showed α-amyrins possess considerable biological activities as nuclear receptor, enzyme inhibitor, GPCR and protease inhibitor ligand. These results clearly demonstrate that α-amyrins could act as potential highly selective COX-/5-LOX inhibitor. Also, it is a safe compound in comparison with classical non-steroidal anti-inflammatory drugs (NSAIDs) that are known as cancer preventive agents, since it is free of side effects on human body and it can be a promising drug for cancer therapeutics., EXCLI Journal; 15:Doc238 ISSN 1611-2156

Background Hepatitis D virus (HDV) is dependent on hepatitis B virus (HBV) infection. Acute infection with HDV can occur simultaneously with acute HBV infection or be superimposed onto a chronic HBV infection. Objectives This study aimed to identify cases of HDV and determine its prevalence in patients with chronic HBV infection for the first time study in Isfahan, central Iran. Patients and Methods In a cross-sectional study in 2009, 346 who had been diagnosed for at least 6 months with chronic HBV were enrolled consecutively. Anti-HDV was measured by ELISA in the serum of these patients. Results The study included 245 males (70.8%) and 101 (29.2%) females with a mean age of 39 ± 12.4 years. Anti-HDV was present in 8 (3.5%) HBe antibody-positive patients (p = 0.36) and in 2 (2.3%) HBe antigen-positive cases (p = 0.68). No association was found between hepatitis D and probable risk factors. Conclusions This study demonstrates that the prevalence of HDV infection is higher in patients who are positive for HBeAb compared those who are HBeAg-positive. Therefore, most HDV antibody-positive cases in Isfahan are HBV/HDV superinfections but not coinfections.

Introduction: The aim of this study was to evaluate diagnostic value of urinary polymerase chain reaction (PCR) in urogenital tuberculosis (UTB). Materials and Methods: In 33 patients with confirmed diagnosis of UTB by urine culture and/or acid-fast staining, clinical symptoms and laboratory and radiological findings were evaluated. For each patient, 3 consecutive urine samples were examined by PCR for Mycobacterium tuberculosis and the results were compared with the standard microbiological methods and radiological findings. Results: The mean interval between the appearance of the symptoms and the diagnosis was 12.3 ± 12.2 months. Symptoms were irritative bladder symptoms such as dysuria and diurnal or nocturnal frequency (51.5%), flank pain (27.3%), microscopic hematuria (18.2%), gross hematuria (9.1%), and suprapubic pain (9.1%). The laboratory findings included hematuria (27.3%), pyuria (12.1%), and hematuria with pyuria (48.5%). Diagnosis of UTB was made in 19 patients by positive urine culture for MT in 19 patients (57.6%), positive acid-fast staining in 6 (18.2%), and both in 8 (24.2%). Intravenous urography showed abnormal findings in 16 patients (61.5%), including pyelocaliceal dilatation (26.9%), ureteral stricture and hydroureter (23.1%), multiple small caliceal deformities (15.4%), severe parenchymal destruction (11.5%), autonephrectomy (11.5%), and calcification (7.7%). Urinary PCR was positive in 16 patients (48.5%) and in 10 (62.5%) with abnormal findings on intravenous urography. Conclusion: A high index of suspicion is necessary for diagnosis of UTB even in patients with nonspecific manifestations. Urinary PCR is recommended for instant diagnosis and screening before further examinations, but it cannot be the sole diagnostic modality for diagnosis of UTB.